Kidney & Pancreas Transplantation in Patients with HIV
INDICATIONS FOR KIDNEY TRANSPLANTATION:
Recommendations:
All potential kidney transplant recipients are screened for HIV infection.
HIV per se is not a contraindication for kidney transplantation.
recommend wait-listing HIV patients only if:
a) They are concordant with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/µL (ideally >200 cells/µL) and have been stable during the previous 3 months.
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
We suggest that the most appropriate anti-retroviral therapy for an individual patient should be discussed with the HIV/infectious disease team before transplantation.
The use of anti-retroviral such as integrase inhibitors that do not inhibit the P-450 system may simplify the use of immunosuppressants in this setting and decrease the frequency of rejection however.
NDICATIONS FOR PANCREAS TRANSPLANTATION:
Recommendations:
Suggest that diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation.
suggest that diabetic patients with severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min). CONTRAINDICATIONS TO TRANSPLANTATION:
Recommendations:
Absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently less than 200cell/micml.
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse.
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART.
d) Positive CDC crossmatch.
e) Serious ongoing or recurring infection, including documented history of PML.
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer.
g) Pregnancy.
Relative contraindications to kidney transplantation:
a) Positive FCXM.
b) Blood-type incompatibility.
c) Treated malignancy, including extra cutaneous Kaposi sarcoma.
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy.
e) Chronic liver disease.
f) Marked obesity (BMI >35 kg/m2).
g) HTLV infection. HIV-SPECIFIC ASSESSMENT:
Careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile.
Solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL in selected cases, should be full adherent to medication.
Its suggest that antiretroviral with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation so do drug interact with CNI (ritonavir and cobicistat)
Recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukemia virus and Toxoplasma Gondi and T.B plus latent T.B. Also, test for HBC, HCV and Strongyloides stercoralis.
Screen for malignancy:
Cervical smear and rectal examination annually PANCREAS-SPECIFIC ASSESSMENT:
Recommendations:
We suggest that pancreas transplantation assessment in patients with HIV includes:
• Diabetic assessment (for hypoglycemic unawareness, peripheral neuropathy, & autonomic neuropathy)
• Vascular assessment (ultrasound assessment of leg vessels, and consider non-contrast CT of aorta and iliac arteries)
• Consideration of a more extensive cardiac assessment.
PRE-TRANSPLANT IMMUNISATION:
Recommendations:
• HBV vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B) • Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D) • Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B) • Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL.
HAV vaccine is administered to all non-immune patients.
• Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients.
• VZV vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL.
Suggest that:
• DTP vaccine is administered to all patients
• MMR) vaccine is administered to all patients who are non-immune to measles
• Human papilloma virus vaccine is offered to patients at risk of HPV acquisition.
Influenza vaccine is administered annually to patients awaiting solid organ transplant.
CONSIDERATION OF DRUG-DRUG INTERACTIONS:
Recommendations
A full and current medication review as part of the assessment for solid organ transplantation
On, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant.
Suggest pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimize drug interactions.
Continuation of antiretroviral therapy in the perioperative period following transplantation.
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION:
Induction with (IL-2RA) and MAINTENANCE with triple therapy.
Treatment of acute rejection:
If antibody mediated rejection, consideration of plasma-exchange, anti-CD20 monoclonal antibody or intravenous immunoglobulin, with or without lymphocyte-depleting agents. POST-TRANSPLANT PROPHYLAXIS:
Recommendations:
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation. The drug of choice for prophylaxis is trimethoprim-sulfamethoxazole (cotrimoxazole) 480 mg once daily. Second line aerosolized pentamidine 300 mg via nebulizer monthly or Dapsone 100 mg once daily. In case of co-trimoxazole or Dapsone allergy, consider Atovaquone 1500 mg once daily or
, lifelong prophylaxis is recommended for Toxoplasma IgG+ subjects with a CD4+ countless than 200 cell/mic ml co-trimoxazole s960 mg once daily is recommended as first line prophylaxis ,although many studies show successful prophylaxis using co-trimoxazole 960 mg thrice weekly for varying durations. An alternative that has been well studied in patients with HIV/AIDS is Dapsone 50 mg once daily plus pyrimethamine 50 mg once weekly.
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3months. Valganciclovir is the preferred prophylactic agent.
Recommend that CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months.
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation.
transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis .
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing.
Treated patient no need for assessment unless there is symptoms or reexposures.
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months. Non-tuberculosis mycobacteria (NTM):
Among HIV-infected persons, a CD4+ T cell count of less than 50cell s associated with increased risk of disseminated NTM infection. . It is therefore suggested that prophylaxis against NTM is indicated when the CD4+ T cell count is ≤50 /µL, and may be stopped when the CD4+ count has been >100 cells/µL for 6 months.
Prophylaxis is with azithromycin 1250 mg once weekly; alternatively clarithromycin 500 mg twice daily or rifabutin 300 mg once daily.
The preferred secondary prophylaxis is with azithromycin 500 mg once daily in combination with ethambutol 15 mg/kg/day; alternatively, clarithromycin 500 mg twice daily plus ethambutol 15 mg/kg/day. MONITORING ALLOGRAFT FUNCTION:
Recommendations:
Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease. MONITORING OF HIV VIROLOGICAL CONTROL:
quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months there t if patients have persistent HIV viremia, drug-resistance testing is carried out to determine treatment options after. CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients. Those potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory. HIV are not suitable donors.
CONSENT AND CONFIDENTIALITY:
Recommend that existing guidelines on the ethics of deceased donor and living donor transplantation be followed, also consent, encourage recipient to disclose their condition to donors.
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS:
Recommendations:
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
– HIV viral load <50 copies/mL and CD4 count >less than 50copies/ml and CD4 count more 200/µL for at least 6 months prior to brain injury.
– Information about the donor virus such as historical genotype patterns where possible and current viral load –
No history of virological failure or drug resistance
Introduction. Scope and aim of guidelines; The aim is to give comprehensive summary guidelines of all aspects of management, prevention, surveillance of the HIV positive transplant recipient. Indications for kidney transplantation. Recommendations; There is no absolute contraindication for trasnpalntation if, They are complaint with treatment, No HIV RNA during the last six months. CD4+T counts >100. No opportunistic infections. Suggestions; Start appropriate dose of HAART therapy. Indication for Pancreas transplantation. Recommendations; Can proceed for transplantation after expert opinion of expert people. If, there is no such dissiminated malignancy, active chronic or acute active infection. Relative contraindication if there is incompatibility as it may worsen the prognosis of graft. General recommendations for HIV specific assessment. Recipient should be screened for all opportunistic infections, prophylaxes for this, if there is any infection, occult malignancy should be treated before proceeding for transplantation. Pre-trasnplantation immunization. HBV, HAV, PPV, VZV, and influenzea vaccination should be done before transplantation. If CD4+T is >200. While MMR, DPT, and HPV vaccine are given to all patients. Choice of living versus deceased donor. Its suggested that it should be disclosed to recipient HIV status is not graded, and HIV infected have the same access to living and deceased donor.
TB: test for latent infection with an interferon-gamma test with or without a concurrent Mantoux test, if positive look for active infection and treat both active and latent infection as in general population
Viral hepatitis screen and treat, Anti-HBc positive “alone” recipients with ATG gets prophylaxis
Cervical and anal neoplasia
Screen for r Strongyloides stercoralis in endemic areas
Pre-transplant immunisation HAV, HBV, influenza, pneumococcal, VZV, DPT, MMR, HPV Drugs: A) ARV
Avoid ARV with nephrotoxic potential ( tenofovir and atazanavir)
Avoid those with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat)
Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org)
B) dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant C) Induction and maintenance immunosuppression
Induction with interleukin-2 receptor antagonist (IL-2RA)
Maintenance with steroid + CNI + antiproliferative
Rejection as non HIV patients Post-transplant prophylaxis
PCP – life long
CMV – as non HIV
MAC: CD count < 50 and stop if > 100
Toxoplasma: IgG+ve recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor positive receive lifelong prophylaxis Monitor HIV RNA and CD4 count post transplant Choice of living versus deceased donor
HIV +ve not suitable for live donation Use of HIV-infected donors for HIV-infected recipients when donor CD4 count > 200 and viral load < 50 in the past 6M with no hx of virological resistance or failure
Transplantation for HIV positive patient
BTS guideline outlined and recommend the indications and process of kidney transplantation and pancreatic transplantation for HIV infected patients.
This guideline insures stability of the general condition with well controlled HIV reflected as maintained CD4 lymphocyte count of preferably more than 200. General indications for kidney transplantaion :
1] No contraindications for HIV patients to have transplantation.
2] HIV screening has to be implemented for all transplant candidates.
3] HIV patient may be considered transplant candidate when they are consistent with HIV medications, in particular the combined anti-retroviral therapy cART.
4] A stable CD4 of more than 100-200 which is stable for at least 3 months.
5] Well control of viral replication, reflected by undetected HIV RNA [RNA copies less than 200copies/ml] for 6 months.
6] Cell mediated immunity is intact, reflected by absence of opportunistic infection for at least 6 months, such as serological tests for syphilis, CMV, HSV, varicella zoster, toxoplasma and mycobacterium.
7] Major complications related to HIV infection have to be excluded.
8] No history of Malignancy such as lymphoma.
9] Absence of CNS involvement, particularly, progressive multifocal leukoencephalopathy.
10] Refuting of chronic infection such as intestinal cryptosporidiosis.
Reflecting on the above mentioned indications, certain features were considered by the guideline as absolute or relative contraindications for kidney transplantation, owing to the exceeding risk of adverse clinical outcome.
In summery, The contraindications for kidney transplantation are: 1] Multidrug resistance HIV. 2] Most importantly, uncontrolled HIV infection demonstrated as a}CD4 count of less than 100 cell/ml for 6 months. b}Persistence of blood HIV RNA for 3 months. 3] Noncompliance of the patient with his medications. 4] Malignancy. 5]PLE Relative contraindications include Obesity with BMI of more than 35 and co-infection with HTLV.
EXECUTIVE SUMMARY OF RECOMMENDATIONS INDICATIONS FOR KIDNEY TRANSPLANTATION Recommendations: • All potential kidney transplant recipients are screened for HIV infection (1D) • HIV per se is not a contraindication for kidney transplantation (1B) • HIV-positive patients are wait-listed only if: – Concordant with treatment, particularly cART therapy (1D) – CD4+ T cell counts are >200 cells/µL and have been stable during the previous 3 months (1B) – HIV RNA has been undetectable during last 6 months (1B) – No opportunistic infections have occurred in last 6 months (1B) – No h/o progressive multifocal leukoencephalopathy (PML), chronic intestinal cryptosporidiosis, or lymphoma (1B) Suggestions: · The most appropriate anti-retroviral therapy (ART) is determined before transplantation in conjunction with an HIV specialist, in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded) CONTRAINDICATIONS TO TRANSPLANTATION Absolute contraindications for kidney transplantation in HIV patients: a) Uncontrolled HIV infection – (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C) b) Habitual and irremediable non-concordance, due to major psychiatric illness, irresolvable psychosocial problems or persistent substance abuse (1D) c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D) d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D) e) Serious ongoing or recurring infection, including documented history of PML (1D) f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D) g) Pregnancy (1D) Relative contraindications to kidney transplantation in HIV patients a) Positive flow cytometric crossmatch (FCXM) (1D) b) ABO-incompatibility (2D) c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C) d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D) e) Chronic liver disease (2D) f) Marked obesity (BMI >35 kg/m2) – (2D) g) HTLV infection (1D) HIV-SPECIFIC ASSESSMENT Recommendations: – All transplant candidates undergo careful immuno-virological and ARV status review, including CD4 cell count, HIV RNA level, current and prior ART, HIV resistance profile and HLA-B57 status. (1D) Suggestions: – In selected cases, SOT may be appropriate – if fully suppressed HIV RNA and CD4 T cell count <200 cells/µL but >100 cells/µL. (2C) – Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C) – ARV with nephrotoxic potential (tenofovir and atazanavir) are avoided for patient of kidney transplantation, if suitable alternatives are available (Not graded) – ARV with significant drug-drug interactions with CNI (ritonavir and cobicistat) are avoided in the setting of SOT, if suitable alternatives are available (2D) Recommendations: – Transplant candidates undergo serologic testing for syphilis, HSV, EBV, CMV, HTLV-1, Varicella Zoster virus and Toxoplasma gondii (1D) – Transplant candidates are tested for latent TB infection with IGRA +/- Mantoux test to follow the testing strategy for immunocompromised (HIV infected) patients in the current NICE Tuberculosis Guidelines (1C)
– Patients who test positive for LTBI are o assessed for any evidence of active tuberculosis disease (1C) o treated for LTBI ac/to NICE TB guidelines, prior to transplantation (1C) – Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C) Suggestions: Screening for Strongyloides stercoralis infection, for candidates from endemic regions, prior to transplantation (2D) Concomitant HBV and HCV – Recommendations: – All transplant candidates are screened for viral hepatitis. Those with HBsAg or HCV Antibody positive should test for HBV- DNA and HCV-RNA level quantitative PCR and undergo investigation for the presence of liver cirrhosis. (1C) – All HBsAg positive patients wait listed for SOT receive treatment to ensure HBV-DNA fully suppressed (1B)
– Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication. (1C)
– Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN-III) or carcinoma in situ should receive treatment prior to transplantation. (1D) Suggestions: – Anti-HBc positive “alone” recipients (HBsAg and DNA negative; donor negative) do not require routine antiviral prophylaxis against HBV reactivation. (2D) – But Anti-HBV prophylaxis may be considered for those received T-cell depleting agents (ATG). (2D) PRE-TRANSPLANT IMMUNISATION Recommendations: As part of the work-up for solid organ transplantation we recommend that: • Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 m IU/mL). (1B) • Hepatitis A virus (HAV) vaccine is administered to all non-immune patients. (1D) • Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients. (1B) • Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL. (1C) Suggestion: • Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D) • Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D) • Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C) We recommend that influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B) CONSIDERATION OF DRUG-DRUG INTERACTIONS Recommendations – Full review of current medication as part of the assessment for SOT, to be repeated at least twice a year, and at every key therapeutic decision point (Not graded) – Continuation of ART in the perioperative period following transplantation (1D) Suggestions: – A dose-finding trial of CNI, prior to SOT in order to determine optimum dose post-transplant. (2D) – Pre-emptive switching away from boosted protease-inhibitors (PI)-based ART regimen, to alternative regimen, in order to minimise drug interactions (2D) – All clinical correspondence to carry a reference to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded) INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION Recommendations – HIV-positive patients for kidney transplant to be offered induction therapy at the time of transplantation. (1C) – Interleukin-2 receptor antagonist (IL-2RA) is preferable induction agent for HIV-positive recipients. (1B) – Triple drug maintenance IS (same as non-HIV patients), including a CNI, an anti-proliferative agent and steroid, to be started at the time of kidney transplantation (1C) Suggestion: Acute rejection is treated in HIV-positive kidney transplant recipients, in the same way as HIV-negative kidney transplant recipients (2D) POST-TRANSPLANT PROPHYLAXIS Recommendations: – HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D) – Toxoplasma IgG seropositive recipients with a CD4 + T-cell count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
– Minimum of 3 months CMV-prophylaxis indicated in CMV (D+/R-): seronegative recipients of organs from CMV seropositive donors (1A)
– CMV seropositive recipients can receive either 3months-prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for 3 months (1A) Transplant patients not assessed nor treated for TB pre-transplant, should be assessed for LTBI and active TB, as recommended for patients prior to transplantation (1C) Transplant patients who are well and were assessed and fully treated for LTBI or disease before transplantation, do not need reassessment for LTBI unless symptomatic or new exposure to tuberculosis (1C) Post-transplant exposed to tuberculosis should be assessed as recommended in current NICE TB guidance on tuberculosis of contact tracing (1C) With reliable prior history of treated TB infection, there is no need for further testing beyond symptom review and chest X-ray; these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D) Suggestion: Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4 + count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months. (2D) MONITORING ALLOGRAFT FUNCTION Recommendations – Guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded) Suggestion: local practice for monitoring of the pancreas allograft is followed (Not graded) MONITORING OF HIV VIROLOGICAL CONTROL Recommendations – Quantitative HIV RNA and CD4+ T-cell counts are measured regularly post Tx – at 1 month, then 2-3 monthly x1 year; and 3-6 monthly thereafter (1B) – Persistent HIV viraemia needs drug-resistance testing to determine alternate treatment options (1D) Suggestion: frequent monitoring of CD4 count in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D) CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR Recommendations – HIV-infected patients can have the same access to living donor kidney transplantation as non-infected patients (1B) – HIV-infected people are unsuitable to be living kidney donors (1D) Suggestion: – Potential donors for HIV-positive recipients are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded) USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS Recommendations: Transplant of organs from HIV-infected individuals be restricted to deceased donors with: – HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury – Information about the donor virus genotype (where possible) and current viral load – No history of virological failure of treatment or drug resistance (1D) · Recipients are to be informed, counselled and they have to give informed consent both at the time of listing and at the time of transplantation (1D) Suggestion: that HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded) · It is recommended that HIV-infected people are unsuitable to be living kidney donors (1D)
Indications for kidney transplantation According to the BTS giudline no contraindication for transplant for HIV positive recepeint .
These patient need to be on HAARt treatment with cd4 count of more than 200 and undetectable HIV RNA .
HIV-positive patients are wait-listed only if–
They are concordant with treatment, particularly cART therapy
CD4+ T cell counts are >100 cells/µL.
General assessment ;
these people need to ahve genarl assessment like Screening for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii
Test for latent Mycobacterium tuberculosis infection with IGRA
Treat TB as per NICE guidance
Hepatitis B surface antigen or hepatitis C antibody positive should be investigated for the presence of liver cirrhosis
Rule out cervical and/or anal neoplasia..
THese patient suppose to haver the prober HAART therapy and better to avoid PI regiem as it may lead to HIV resistance and drug -drug interaction .
Pre transplant we need to have an idea about the status of HIV resistance if any .
Cnotranindication for transplantation;
Positive CDC crossmatch
Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer ,Pregnancy.
Multi-drug resistant HIV infection that cannot be controlled with currently available ART
INDUCTION AND IS
better to induce induction through BASILIXMIAB AND AVOID ATG.
try to use the IS and regular monitor for the interaction between HAART therapy and CNI.as it will affect the level under the curve irrespect to the trough level ,and this is could be the cause of rejection .
Still we go for HIV + donor for HIV +recipent :
the donor with good general health and imnmunity and CD4 of more than 200
Information about the donor virus such as historical genotype patterns where possible and current viral load
No history of virological failure or drug resistance
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation
Patients with HIV-infection are unsuitable to be living kidney donors
INTRODUCTION: Scope and aim of the guidelines:
As the introduction of highly active antiretroviral therapy (HAART) in 1996, mortality in patients with human immunodeficiency virus (HIV) infection has decreased.
HIV patients are at risk of the development of chronic kidney disease and, end-stage kidney disease (ESRD) and dialysis substantially increase the risk of death and cardiovascular events in both the general and HIV-infected populations.
The aim is to provide a comprehensive summary of all aspects of assessment, selection and management of the HIV-positive transplant candidate. Grading of recommendation:
For each recommendation the quality of evidence has been graded as: A (high) B (moderate) C (low) D (very low) For each recommendation, the strength of recommendation has been indicated as one of: Level 1 (we recommend) Level 2 (we suggest) Not graded (where there is not enough evidence to allow formal grading) Indications for Kidney transplantation: Recommendations:
HIV positive patients is not contraindicated for kidney transplantation if :
1) They are concordant with treatment,(1D)
2) CD4+ T cell counts are >100 cells/µL and have been
stable during the previous 3 months (1B)
3) No HIV RNA during the previous 6 months (1B)
4) No infections during the previous 6 months (1B)
5) No history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma (1B) suggestion:
The most appropriate anti-retroviral therapy is determined before transplantation to anticipate potential drug interactions and dosing (not graded) Indications for Pancreas Transplantation: Recommendation:
HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation , and also in solitary pancreas or islet transplantation (Not graded) Suggestion: Diabetic patients with renal failure and controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D) Contraindications to transplantation: Recommendations:
Absolute contraindications to kidney transplantation in patients with HIV are: Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D), Pregnancy (1D) and uncontrolled HIV infection during the last 6 months(1C). Suggestions:
Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection. General assessment: Recommendations:
Follow existing guidelines for HIV transplant recipients (not graded) HIV-specific assessment: Recommendations:
All transplant candidates undergo careful immuno-virological and antiretroviral status review(1D),serlogy for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D), latent Mycobacterium tuberculosis infection(1C),and screened for viral hepatitis B and C (1C).
hepatitis B surface antigen positive recipients receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
patients with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D). Not recommended: Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) ,active HCV replication (1C), and a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1D) Suggestions:
Solid organ transplantation may be appropriate for patients with suppressed HIV RNA, CD4 cell count below 200 cells/µL, nephrotoxic potential, significant drug-drug interactions with calcineurin inhibitors, and Strongyloides stercoralis infection. Pancreas-specific assessment: Recommendations:
Transplant candidates are counselled for the little experience of pancreas transplantation performed in HIV-infected patients (Not graded) Suggestions:
Pancreas transplantation assessment includes diabetic assessment, vascular assessment, and cardiac assessment (2C). Pre-transplant immunization: Recommendations:
HBV (1B),HAV(1D), PPV-23(1B), VZV (1C), and influenza(1B) vaccines are administrated to non-immune patients with CD4 cell counts >200 cells/µL. Suggestions:
DPT (2D), MMR(2D), and HPV (2C) vaccines are administrated to all patients Consideration of drug-drug interactions: Recommendations:
Continuation of antiretroviral therapy post transplantation (1D) Suggestions:
Continuation of antiretroviral therapy in the perioperative period following transplantation (not graded), dose-finding trial of calcineurin inhibitors prior to transplantation(2D), pre-emptive switching away from PI regimens(2D), and referral to Liverpool HIV Drug Interactions Resource (not graded). Induction and maintenance immunosuppression: Recommendations:
Induction therapy is with IL-2RA (1B), followed by triple therapy maintenance immunosuppression (steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent. (1C) Suggestions:
Acute rejection in HIV-positive and HIV-negative kidney transplant recipients treated as the same (2D) Post-transplant prophylaxis: Recommendations:
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia(1D), cytomegalovirus (1A), and Mycobacterium tuberculosis (1C), as recommended for patients prior to transplantation. Suggestions:
Toxoplasma IgG seropositive recipients with a CD4+ count<200 cells/µL receive lifelong prophylaxis (2C) Monitoring allograft function: Recommendations: Follow existing guidelines for post-operative care of kidney transplant recipients with HIV disease (Not graded) Suggestions:
Follow local practice for monitoring of the pancreas allograft (Not graded) Monitoring of HIV virological control: Recommendations:
Quantitative HIV RNA and CD4+ T-cell counts are measured, followed by drug-resistance testing to determine treatment options. Suggestions:
Monitoring of CD4 count in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D) Choice of living versus deceased donor: Recommendations:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients(1B) Suggestions:
Disclosure of the recipient’s HIV status is not mandatory (Not graded) Consent and confidentiality: Recommendations:
Transplant teams must be satisfied that donor consent is adequate, and procedures are transparent and established. (not graded) Suggestions:
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, Use of HIV-infected donors for HIV-infected recipients: Recommendations:
Transplantation using organs from deceased donors with HIV-infected individuals is restricted to those with HIV viral load <50 copies/mL and CD4 count >200/µL prior to brain injury.
Recipients are counseled and informed before transplantation, and HIV infection is unsuitable for living kidney donors. Suggestions:
HIV+ organ use is restricted to those centers that have experience in transplanting HIV+ patients (Not graded) BACKGROUND:
The use of combination antiretroviral therapy (cART) has led to a dramatic reduction in opportunistic infections and death.
22% of patients in the UK remain unaware of their HIV diagnosis, and approximately half of those newly diagnosed with HIV infection present late
Immunodeficiency is an important risk factor for chronic kidney disease (CKD) and end-stage kidney disease (ESRD) , and for liver disease progression in HCV-co-infected patients. End-stage kidney disease and kidney transplantation in HIV positive patients:
HIV-associated nephropathy is the most severe form of CKD and the most common cause of ESRD in HIV-positive patients in the UK. Kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise eligible., with 1% of black HIV-positive and 0.1% of other ethnicities requiring renal replacement therapy. Diabetes mellitus and pancreas transplantation:
Increased risk of diabetes mellitus itself is not associated with HIV infection.
The use of cART is associated both with the metabolic syndrome and with diabetes mellitus.
Simultaneous pancreas and kidney transplantation (SPK) has been performed in a small number of HIV-positive patients with poor outcome. INDICATIONS FOR KIDNEY TRANSPLANTATION: Recommendations:
Transplant indicated if HIV patients has:
Concordant with treatment, have CD4+ T cell counts >100 cells/µL, have undetectable HIV RNA, and have no history of progressive multifocal leukoencephalopathy. Rationale:
Kidney transplant patients should be screened for HIV infection to identify who need special care.
Data shows that patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation,
Some studies show higher acute rejection rates. INDICATIONS FOR PANCREAS TRANSPLANTATION: Recommendations:
Diabetic patients with severe hypoglycemia considered for simultaneous kidney and pancreas transplantation if HIV and kidney function.is stable. Rationale:
HIV-positive patients with diabetes mellitus undergoing kidney and pancreas transplantation should be counselling for higher risk procedure and its complications. Contraindication for pancreas transplantation: Recommendations:
Absolute contraindications include uncontrolled HIV infection, habitual and irremediable non-concordance, multi-drug resistant HIV infection, serious ongoing or recurring infection, active malignancy, and pregnancy. Suggestions:
Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection. Rationale:
The general criteria applicable to non-HIV kidney transplant waiting lists also apply with some criteria specific to patients with HIV.
The complement-dependent cytotoxicity (CDC) test detects complement-fixing IgG and IgM antibodies and is positive when there are high levels of circulating antibodies specific for mismatched donor HLA antigens present at the time of transplantation.
The flow cytometric crossmatch (FCXM) detects lower levels of anti-HLA antibodies and is not associated with an increased risk of hyperacute rejection but does predict early acute rejection and premature graft failure.
Infectious complications following solid-organ transplantation are common and may be life or graft-threatening.
Solid organ transplant recipients are at high risk of occurrence of cancer including human papilloma virus-associated cervical and anal carcinoma.
Cardiovascular disease is the main cause of mortality after transplantation.
Recipients with a body mass index over 35 kg/m2 are at increased risk of complications after kidney transplantation. GENERAL ASSESSMENT: Recommendation:
Existing guidelines regarding evaluation, selection, and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded) Rationale
HIV-infected and non-HIV-infected kidney and pancreas transplant candidates should be assisted as the same in pre-transplant period. HIV-SPECIFIC ASSESSMENT: Recommendations:
All transplant candidates undergo careful immuno-virological and antiretroviral status review(D).
Serologic testing for CD4 cell count, HIV RNA level, HLA-B5701 status, nephrotoxic potential, and latent Mycobacterium tuberculosis infection.
SOT must be avoided in patients with liver cirrhosis, cervical and/or anal neoplasia, extra-cutaneous Kaposi sarcoma, Castleman’s disease, HHV8-related primary effusion lymphoma or EBV-related lymphoma. Rationale:
Patients must be assessed pre-transplant so as to decrease infectious complications and formulate a management plan that allows safe co-administration of combination antiretroviral therapy and immunosuppression.
SOT may be done for patients with markedly suppressed HIV RNA and an absolute CD4 cell count below 200 cells/µL Screening for latent infections:
Its important to screen for may viruses in pre-transplant period to avoid its complications and for immunization. Viral hepatitis:
The prevalence of hepatitis B (HBV) and hepatitis C (HCV) is increased in HIV-positive patients. HIV-positive patients with replicating HBV co-infection who are listed for kidney and/or pancreas transplantation should be treated with nucleoside or nucleotide analogues to render them aviraemic prior to and after transplantation. Malignancy:
HPV-associated cancer rates is increased in both HIV-positive patients and kidney transplant recipients, so annual screening must done by cervical smear and colonoscopy to exclude intra-epithelial neoplasia. Pancreas specific assessment: Recommendations:
HIV-infected patients who undergo pancreas transplantation assessment should be done in a center that regularly performs renal transplantation (1C.). Rationale:
Patients who undergo for pancreas transplantation should be assessed for hypoglycemic unawareness, peripheral neuropathy, and autonomic neuropathy. Pre-transplant immunization: Recommendations:
All non-immune patients with CD4 cell counts >200 cells/µL. must be vaccinated. Suggestions:
All patients must have diphtheria, tetanus, and pertussis (DTP) vaccine, non-immune patients must have measles, mumps, and rubella (MMR) vaccine and who at risk must have HPV vaccine.
Influenza vaccine must be given annually to patients awaiting for solid organ transplantation (1B) Rationale: Hepatitis B virus (HBV):
HIV-positive patients are at increased risk of chronic HBV infection, with an increased risk of cirrhosis and liver cancer. Hepatitis A virus (HAV):
HAV vaccine is safe and well tolerated in HIV-infected patients and those with end-stage kidney disease. Pneumococcus:
Pneumococcal vaccination must be given to HIV-positive patients with CD4 cell counts >200 cells/µL and <200 cells/ µL if there is risk factor. Repeated every 3-5 years. Varicella-Zoster virus (VZV):
VZV vaccination recommended for asymptomatic, VZV IgG seronegative HIV positive adults with a CD4 cell count >400 cells/µL. Diphtheria, Tetanus and Pertussis (DTP):
DTP vaccine is safe for HIV-positive patients. Measles, mumps, and rubella (MMR):
MMR vaccine must be given to HIV+ve patients if they are measles IgG seronegative and asymptomatic with a CD4 count >200 cells/µL Human papilloma virus (HPV):
HIV-positive patients and solid organ transplant recipients with anogenital HPV infection are at substantially increased risk of developing cervical and anogenital cancers.
Vaccination of HIV-positive young adults may reduce the risk of cervical and anogenital cancer. Influenza:
All HIV-positive patients, especially those with serious medical conditions must have influenza vaccine. CONSIDERATION OF DRUG-DRUG INTERACTIONS: Recommendations:
Medication review, dose-finding trial, pre-emptive switching, the continuation of antiretroviral therapy, and referral to Liverpool HIV Drug Interactions Resource. Rationale:
Drug reconciliation is essential to ensure accurate and up-to-date documentation of all prescribed medicines at the time of transplantation and predict potential interactions between them and immunosuppressants.
A dose-finding trial of CNI immunosuppression with therapeutic drug monitoring is recommended to optimize CNI concentrations following transplantation. INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION: Recommendations:
HIV-positive patients eligible for kidney transplantation are offered induction therapy (triple) at the time of transplantation (1C)
HIV-positive kidney transplant recipients with acute rejection treated as same as HIV-negative kidney transplant recipients (2D). Rationale:
The HIV-TR Investigators’ study found that conventional immunosuppression is a risk for HIV-positive kidney transplant recipients. Induction agents:
IL-2 receptor antagonists (IL-2RA) is superior to placebo in HIV negative kidney transplantation.
lymphocyte-depleting agents are associated with lower rejection rates and reduced graft loss. Maintenance immunosuppression:
The maintenance regimens for non-HIV kidney transplant recipients are: tacrolimus, mycophenolate, and prednisolone. Management of acute rejection:
Corticosteroids and augmented background immunosuppression, with or without lymphocyte-depleting agents is the main treatment of acute T-cell mediated rejection. POST-TRANSPLANT PROPHYLAXIS: Recommendations:
HIV-positive transplant recipients must receive lifelong prophylaxis against pneumocystis pneumonia, toxoplasma IgG seropositive recipients with CD4+ count <200 cells/µL, cytomegalovirus, CMV seronegative recipients, and MAC Rationale:
HIV-positive transplant recipients are at increase risk of opportunistic infections so they need stringent prophylactic regimens. Pneumocystis pneumonia (PCP):
Non-HIV-infected solid organ transplant recipients may need PCP prophylaxis for at least 3-6 months post-transplant. Toxoplasma gondii:
Co-cotrimoxazole is the most effective prophylaxis against toxoplasmosis in HIV-positive patients, but dapsone and pyrimethamine are also effective. Cytomegalovirus:
Prevented by antiviral prophylaxis and pre-emptive therapy. Mycobacterium tuberculosis (TB):
According to NICE guidelines transplanted patient must be assessed for latent and TB infection. Non-tuberculosis mycobacteria (NTM):
Prophylaxis with azithromycin 1250 mg once weekly, clarithromycin 500 mg twice daily or rifabutin 300 mg once dailyis indicated when CD4+ T cell count is <50/µL for 6 months. MONITORING ALLOGRAFT FUNCTION: Recommendations:
Follow local practice (not graded). Rationale:
Post-operative care should be the same for HIV-infected and non-infected kidney and pancreas transplant candidates. MONITORING OF HIV VIROLOGICAL CONTROL: Recommendations:
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months thereafter (1B)
Patients who have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D). Rationale:
Anti-viral treatment that is insufficient to completely suppress viral replication imposes a selective pressure that may result in the emergence of drug-resistant viral escape mutants. HIV drug resistance testing is thus part of the standard management of patients in whom viral replication is not suppressed. CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR: Recommendations:
Patients with HIV infection should have the same access to living donor kidney transplantation as non-infected patients. Rationale:
Living kidney donation yields superior outcomes relative to deceased donor transplantation.
HIV-infected patients may encounter unique barriers to living donor kidney transplantation.
It is important to work collaboratively with potential donors and recipients to ensure an informed risk-benefit assessment and there may be a need to tailor pre-transplantation. CONSENT AND CONFIDENTIALITY: Recommendations:
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded).
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded). Rationale: Existing guidelines:
Good ethical practice consistently underpins clinical practice to achieve optimum outcomes. No longer an ‘experimental’ procedure:
The risks and benefits of transplantation for HIV patients should be discussed in the same way as those for other co-morbidities. Particular issues relating to the disclosure of a diagnosis of HIV in living donation:
Living kidney donation may involve conflict between donor consent and recipient confidentiality, so it is important to have consent from the recipient to openly discuss medical conditions.
Transplant teams should ask potential donors if there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV. Confidence of the transplant team in the consent process while respecting recipient and donor confidentiality:
Transplant teams agree that donor consent is adequate and that procedures for ensuring this is transparent and established, but not at the expense of confidentiality. USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS: Recommendations:
HIV+ve patients is restricted to organs from deceased donors with HIV viral load <50 copies/ML and CD4 count >200/µL for at least 6 months prior to brain injury.
HIV+ve patients are unsuitable to be living kidney donor(1D). Rationale:
HIV-infection is regarded as an absolute medical contra-indication to organ donation by many transplant centers. However, advances in care for patients with HIV, increasing waiting times, and reports of organ donation from HIV-infected (but treatment-naïve or receiving only first line ART) individuals in South Africa showing favorable outcomes at 3 to 5 years, suggest that this approach should be reconsidered.
INTRODUCTION Scope and aim of the guidelinesThe introduction of highly active antiretroviral therapy (HAART) in 1996 has decreased mortality in patients with HIV, but morbidity from other chronic conditions such as kidney, liver, and heart disease has increased.
HIV-infected patients are at particular risk of the development of chronic kidney disease and end-stage kidney disease (ESRD) and dialysis, which increase the risk of death and cardiovascular events.
These guidelines reflect the growing evidence base from published data on the several hundred carefully selected patients with HIV infection who have already received kidney and pancreas transplants.
Indications for Kidney transplantation Recommendations:
HIV is not a contraindication for kidney transplantation, but HIV-positive patients must be concordant with treatment and have stable CD4+ T cell counts, undetectable HIV RNA, and no opportunistic infections. Suggestions:
The most appropriate anti-retroviral therapy is determined before transplantation to anticipate potential drug interactions and dosing.
Indications for Pancreas Transplantation Recommendations:
HIV-positive pancreas transplant recipients are assessed by a center with experience in kidney and islet transplantation. Suggestions:
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have stable HIV and kidney function.
Contraindications to transplantation Recommendations:
Contraindications to kidney transplantation in patients with HIV include uncontrolled HIV infection, habitual and irremediable non-concordance, multi-drug resistant HIV infection, serious ongoing or recurring infection, active malignancy, metastatic cancer, and pregnancy. Suggestions:
Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection.
General assessment Recommendations:
Existing guidelines are followed for HIV transplant recipients. HIV-specific assessment Recommendations:
All transplant candidates undergo immuno-virological and antiretroviral status review, serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human T-cell leukemia virus, and Toxoplasma gondii, and latent Mycobacterium tuberculosis infection.
Hepatitis B surface antigen or hepatitis C antibody positive should be quantified and investigated for liver cirrhosis. Not recommended:
Kidney and/or pancreas transplantation in patients with liver cirrhosis, HCV replication, Castleman’s disease, HHV8, and EBV. Suggestions:
Solid organ transplantation may be appropriate for patients with suppressed HIV RNA, CD4 cell count below 200 cells/µL, nephrotoxic potential, significant drug-drug interactions with calcineurin inhibitors, and Strongyloides stercoralis infection.
Pancreas-specific assessment Recommendations:
Transplant candidates are carefully counseled and informed of the limited experience of pancreas transplantation in HIV-infected patients. Suggestions:
Pancreas transplantation assessment includes diabetic assessment, vascular assessment, and cardiac assessment.
Pre-transplant immunisation Recommendations:
HBV, HAV, PPV-23, VZV, and influenza vaccines are administered to non-immune patients with CD4 cell counts >200 cells/µL. Suggestions:
Diphtheria, tetanus, and pertussis (DTP) vaccine are administered to all patients, measles, mumps, and rubella (MMR) to non-immune patients, and the HPV vaccine to those at risk.
Consideration of drug-drug interactions We recommend: Continuation of antiretroviral therapy in the post-transplant period. We suggest:
Continuation of antiretroviral therapy in the perioperative period following transplantation, dose-finding trial of calcineurin inhibitors prior to transplantation, pre-emptive switching away from PI regimens, and referral to Liverpool HIV Drug Interactions Resource.
Induction and maintenance of immunosuppression Recommendations:
Induction therapy is with IL-2RA, followed by triple therapy maintenance immunosuppression. Suggestions:
Acute rejection in HIV-positive kidney transplant recipients is treated the same as in HIV-negative recipients.
Post-transplant prophylaxis Recommendations:
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia, cytomegalovirus, and Mycobacterium tuberculosis, as recommended for patients prior to transplantation. Suggestions:
Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL receive lifelong prophylaxis, while those with a prior history of TB infection do not require it unless TB re-exposure is suspected.
Monitoring allograft function Recommendations:
Post-operative care for HIV-positive kidney transplant recipients is followed.
Pancreas allograft monitoring is done according to local practice.
Monitoring of HIV virological control Recommendations: Quantitative HIV RNA and CD4+ T-cell counts are measured, followed by drug-resistance testing to determine treatment options. Suggestions:
Monitor CD4 count to determine the need for anti-infective prophylaxis.
Choice of living versus deceased donor Recommendations:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients. Suggestions: Disclosure of HIV status is not mandatory for potential donors.
Consent and confidentiality Recommendations: Transplant teams must be satisfied that donor consent is adequate and procedures are transparent and established. Suggestions:
Living donors are asked if there are any medical conditions that could change their decision to donate, and to acknowledge that they will not be given confidential information about the recipient.
Use of HIV-infected donors for HIV-infected recipients Recommendations:
Transplantation using organs from deceased donors with HIV-infected individuals is restricted to those with HIV viral load <50 copies/mL and CD4 count >200/µL prior to brain injury.
Recipients are counseled and informed before transplantation, and HIV infection is unsuitable for living kidney donors. Suggestions:
HIV+ organ use is restricted to those centers that have experience in transplanting HIV+ patients (Not graded)
BACKGROUNDThe use of combination antiretroviral therapy (cART) has led to a dramatic reduction in opportunistic infections and death in the UK, but 22% of patients remain unaware of their HIV diagnosis, and half of those newly diagnosed present late are at increased risk of opportunistic infections.
End-stage kidney disease and kidney transplantation in HIV-positive patientsHIV-associated nephropathy is the most severe form of CKD and the most common cause of ESRD in HIV-positive patients in the UK. Kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise eligible., with 1% of black HIV-positive and 0.1% of other ethnicities requiring renal replacement therapy.
Diabetes mellitus and pancreas transplantationHIV infection is not associated with an increased risk of diabetes mellitus, but cART has been associated with metabolic syndrome and diabetes mellitus. SPK has been performed in a small number of HIV-positive patients, but poor outcomes have been reported.
INDICATIONS FOR KIDNEY TRANSPLANTATIONRecommendations
HIV per se is not a contraindication for kidney transplantation, but wait-listing HIV patients only if they are concordant with treatment, have CD4+ T cell counts >100 cells/µL, have undetectable HIV RNA, and have no history of progressive multifocal leukoencephalopathy. RationaleScreening for HIV infection should be carried out on all potential kidney transplant recipients to identify those that will require specialized care.
Data on several hundred carefully selected HIV-positive patients to show that patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation, but some studies report disturbingly high acute rejection rates.
The high rejection rate may be due to difficulty in obtaining a good balance between immunosuppression and controlled viral replication, and antiretrovirals such as integrase inhibitors may simplify the use of immunosuppressants and decrease the frequency of rejection.
INDICATIONS FOR PANCREAS TRANSPLANTATIONRecommendations
Diabetic patients with severe hypoglycaemic unawareness may be considered for simultaneous kidney and pancreas transplantation if they have stable HIV and kidney function. RationalePancreas-kidney transplants can be performed in HIV-positive patients with diabetes mellitus, but with a higher risk of procedure-related complications. Careful counseling is needed.
CONTRAINDICATIONS TO TRANSPLANTATION Recommendations Contraindications to kidney transplantation in patients with HIV include uncontrolled HIV infection, habitual and irremediable non-concordance, multi-drug resistant HIV infection, serious ongoing or recurring infection, active malignancy, and pregnancy. Suggestions Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection.
Rationale The general criteria applicable to non-HIV kidney transplant waiting lists also apply to patients with HIV. CDC test detects complement-fixing IgG and IgM antibodies and is positive when there are high levels of circulating antibodies specific for mismatched donor HLA antigens. FCXM detects lower levels of anti-HLA antibodies and is not associated with an increased risk of hyperacute rejection, but does predict early acute rejection and premature graft failure. Hepatitis B or C infection may be a contraindication, but quiescent disease and a benign liver biopsy can proceed. Recipients with a body mass index over 35 kg/m2 are at increased risk of complications, such as surgical complications, a longer length of stay, increased mortality, and a higher risk of post-transplant diabetes mellitus.
GENERAL ASSESSMENTRecommendation
Existing guidelines regarding evaluation, selection, and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded)
Rationale
Pre-transplant assessment should not be different for HIV-infected and non-HIV-infected kidney and pancreas transplant candidates.
HIV-SPECIFIC ASSESSMENT Recommendations
All transplant candidates should undergo careful immuno-virological and antiretroviral status review and serologic testing for CD4 cell count, HIV RNA level, HLA-B5701 status, nephrotoxic potential, and latent Mycobacterium tuberculosis infection.
Solid organ transplantation should be avoided in those with liver cirrhosis, cervical and/or anal neoplasia, extra-cutaneous Kaposi sarcoma, Castleman’s disease, HHV8-related primary effusion lymphoma or EBV-related lymphoma.
RationaleThe pre-transplant assessment aims to minimize infectious complications and formulate a management plan that allows safe co-administration of combination antiretroviral therapy and immunosuppression.
Solid organ transplantation may be an option for patients with fully suppressed HIV RNA and an absolute CD4 cell count below 200 cells/µL.
Screening for latent infectionsImmunization should be offered to all VZV IgG-negative patients with CD4 cell counts >200 cells/µL, and specialist advice should be sought before wait listing HTLV-1 positive transplant candidates. LTBI should be actively sought and treated prior to solid organ transplantation, and IGRAs are more sensitive and specific than tuberculin skin tests to detect LTBI.
Viral hepatitisHIV-positive patients with replicating HBV co-infection should be treated with nucleoside or nucleotide analogs to render them aviraemic prior to and after transplantation.
Malignancy HIV-positive patients and kidney transplant recipients should have annual cervical smears and colposcopy to exclude intraepithelial neoplasia.
PANCREAS-SPECIFIC ASSESSMENTRecommendations Pancreas transplantation assessment in HIV-infected patients should be performed in a center that regularly performs renal transplantation and 1C.
Rationale
Patients being assessed for pancreas transplantation should be assessed for hypoglycaemic unawareness, peripheral neuropathy, and autonomic neuropathy.
PRE-TRANSPLANT IMMUNISATION
Recommendations Vaccines are recommended for non-immune patients with CD4 cell counts >200 cells/µL. Suggestions:Diphtheria, tetanus, and pertussis (DTP) vaccine are administered to all patients, the measles, mumps, and rubella (MMR) vaccine to non-immune patients, and the HPV vaccine to those at risk. We recommend that the influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
Rationale Hepatitis B virus (HBV) HIV-positive patients are at increased risk of chronic HBV infection, with an increased risk of cirrhosis and liver cancer. Hepatitis A virus (HAV) HIV vaccine is safe and well tolerated in HIV-infected patients and those with end-stage kidney disease. PneumococcusPneumococcal vaccination is recommended for HIV-positive patients with CD4 cell counts >200 cells/µL. Varicella-Zoster virus (VZV)VZV vaccination is recommended for asymptomatic, VZV IgG seronegative HIV-positive adults with a CD4 cell count >400 cells/µL. Diphtheria, tetanus, and pertussis (DTP) BHIVA recommends vaccination for all HIV-positive persons in accordance with standard recommendations. Measles, mumps, and rubella (MMR) Two doses of MMR vaccine must be given to HIV-positive persons with seronegative and asymptomatic CD4 count >200 cells/µL. Human papilloma virus (HPV)
HIV-positive patients and solid organ transplant recipients are at increased risk of cervical and anogenital cancers.
Vaccination of HIV-positive young adults may reduce the risk of cervical and anogenital cancer
Influenza
Vaccination is recommended for all HIV-positive patients, especially those with serious medical conditions.
CONSIDERATION OF DRUG-DRUG INTERACTIONSRecommendations
Medication review, dose-finding trial, pre-emptive switching, the continuation of antiretroviral therapy, and referral to Liverpool HIV Drug Interactions Resource.
RationaleDrug reconciliation is essential to ensure accurate and up-to-date documentation of all prescribed medicines at the time of transplantation and predict potential interactions between them and immunosuppressants. A dose-finding trial of CNI immunosuppression with therapeutic drug monitoring is recommended to optimize CNI concentrations following transplantation.
INDUCTION AND MAINTENANCE OF IMMUNOSUPPRESSIONRecommendationsHIV-positive patients should be offered induction therapy at the time of transplantation, triple therapy, and acute rejection treated in the same way as HIV-negative recipients.
Rationale The HIV-TR Investigators’ study found that conventional immunosuppression is a risk for HIV-positive kidney transplant recipients.
Induction agents
IL-2 receptor antagonists have been shown to be superior to placebo in HIV-negative kidney transplantation, but lymphocyte-depleting agents are associated with lower rejection rates and reduced graft loss. The evidence base for the use of lymphocyte-depleting agents in HIV-positive kidney transplantation is limited.
Maintenance immunosuppression Tacrolimus, mycophenolate, and prednisolone are the best maintenance immunosuppressive regimens for non-HIV kidney transplant recipients. The most effective combination in non-HIV kidney transplantation is tacrolimus, mycophenolate, and prednisolone.
Management of acute rejectionTreatment of acute T-cell mediated (cellular) rejection should be with corticosteroids and augmented background immunosuppression, with or without lymphocyte-depleting agents.
POST-TRANSPLANT PROPHYLAXIS Recommendations
HIV-positive transplant recipients should receive lifelong prophylaxis against Pneumocystis pneumonia, Toxoplasma IgG seropositive recipients with CD4+ count <200 cells/µL, cytomegalovirus, CMV seronegative recipients, and MAC.
RationaleHIV-positive transplant recipients may require more stringent prophylactic regimens due to the increased risk of opportunistic infections.
Pneumocystis pneumonia (PCP)
Anti-Pneumocystis prophylaxis is recommended for non-HIV-infected solid organ transplant recipients for at least 3-6 months post-transplant, but longer durations may be considered.
Toxoplasma gondii
Co-cotrimoxazole is the most effective prophylaxis against toxoplasmosis in HIV-positive patients, but dapsone and pyrimethamine are also effective.
CytomegalovirusAntiviral prophylaxis and pre-emptive therapy are two major strategies for CMV prevention.
Mycobacterium tuberculosis (TB)Transplant patients should be assessed for latent TB infection or disease in accordance with NICE guidance.
Non-tuberculosis mycobacteria (NTM) Prophylaxis against NTM is indicated when CD4+ T cell count is <50/µL for 6 months, with azithromycin 1250 mg once weekly, clarithromycin 500 mg twice daily or rifabutin 300 mg once daily.
MONITORING ALLOGRAFT FUNCTIONRecommendations
Local practices for monitoring pancreas allografts should be followed.
Rationale
Post-operative care should not be different for HIV-infected and non-infected kidney and pancreas transplant candidates. MONITORING OF HIV VIROLOGICAL CONTROLRecommendations
Monitoring HIV RNA and CD4+ T-cell counts regularly to determine need for anti-infective prophylaxis.RationaleStudies have shown that CD4+ cell counts can be affected by the type of immunosuppressive agents used, with thymoglobulin induction being associated with a greater decline in CD4+ T-cells in the first year after transplant. Anti-viral treatment that is insufficient to completely suppress viral replication imposes selective pressure, leading to the emergence of drug-resistant viral escape mutants.
CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR Recommendations: Patients with HIV infection should have the same access to living donor kidney transplantation as non-infected patients, but disclosure of HIV status is not mandatory. RationaleLiving kidney donation yields superior outcomes, but HIV-infected patients may face unique barriers. It is important to work collaboratively with potential donors and recipients to ensure an informed risk-benefit assessment and tailor pre-transplantation education to address the unique circumstances of this patient subgroup.
CONSENT AND CONFIDENTIALITYRecommendationsThe most important details are that the standard of consent for HIV-positive transplant candidates is the same as for any other transplant, that the recipient is encouraged to disclose their diagnosis of HIV to their donor, that all living donors are made aware that there may be medical and social information about the recipient that is not disclosed, and that transplant teams must be satisfied that donor consent is adequate.
RationaleExisting guidelinesGood ethical practice is essential for successful transplantation, with BTS Ethics Committee providing support and advice.
No longer an ‘experimental’ procedureThe risks and benefits of transplantation for HIV patients should be discussed in the same way as those for other co-morbidities.
Particular issues relating to the disclosure of a diagnosis of HIV in living donationLiving kidney donation may involve conflict between donor consent and recipient confidentiality, so it is important to have consent from the recipient to openly discuss medical conditions. Transplant teams should ask potential donors if there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV.
Confidence of the transplant team in the consent process while respecting recipient and donor confidentiality Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this is transparent and established, but not at the expense of confidentiality.
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS Recommendations: HIV+ organ use should be restricted to deceased donors with HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury.
RationaleHIV infection is not an absolute medical contra-indication to organ donation, but advances in care for patients with HIV, increasing waiting times, and reports of organ donation from HIV-infected (but treatment-naïve or receiving only first-line ART) individuals suggest it should be reconsidered. Pre-implantation biopsies may detect donor disease, but there is a risk of organ misallocation leading to transmission of HIV to uninfected recipients.
• All potential kidney transplant recipients are screened for HIV infection (1D)
• HIV per se is not a contraindication for kidney transplantation (1B)
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that:
• The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
INDICATIONS FOR KIDNEY TRANSPLANTATION
Recommendations
We recommend that all potential kidney transplant recipients are screened for HIV infection (1D)
We recommend that HIV per se is not a contraindication for kidney transplantation (1B)
We recommend wait-listing HIV patients only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally >200 cells/µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that the most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
CONTRAINDICATIONS TO TRANSPLANTATION
Recommendations
We recommend that the following transplantation in patients with HIV:
are
absolute
contraindications
to
kidney
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <200 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
We suggest that the following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2 ) (2D)
g) HTLV infection (1D)
HIV-SPECIFIC ASSESSMENT
Recommendations
We recommend that all transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
We suggest that in selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
We recommend that patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
We suggest that antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded)
We suggest that antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D)
We recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection following the testing strategy for immunocompromised HIV infected patients in the current NICE Tuberculosis Guidelines (1C)
recommend that transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
We recommend that transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
We recommend that transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
We suggest that transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
We recommend that all transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and undergo investigation for the presence of liver cirrhosis (1C)
We recommend that all hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
We suggest that anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
We recommend that patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
PRE-TRANSPLANT IMMUNISATION
Recommendations
As part of the work-up for solid organ transplantation we recommend that:
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
• Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
• Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
• Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
We suggest that:
• Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
• Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D)
• Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
We recommend that influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
CONSIDERATION OF DRUG-DRUG INTERACTIONS
Recommendations
We suggest a full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
We suggest a dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
We suggest pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
We recommend continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
We suggest that all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION
Recommendations
We recommend that all HIV-positive patients eligible for kidney transplant offered induction therapy at the time of transplantation (1C)
We recommend that for the majority of HIV-positive patients induction thera an interleukin-2 receptor antagonist (IL-2RA) (1B)
We recommend that HIV-positive patients are given triple therapy mai immunosuppression started at the time of kidney transplantation, including a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
We suggest that acute rejection is treated in HIV-positive kidney transplant r in the same way as HIV-negative kidney transplant recipients (2D)
POST-TRANSPLANT PROPHYLAXIS
Recommendations
We recommend that HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
We suggest that Toxoplasma IgG seropositive recipients with a CD4 + count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
We recommend that prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
We recommend that CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C)
We suggest that where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
We suggest that prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4 + count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
MONITORING ALLOGRAFT FUNCTION
Recommendations
We recommend that existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
We suggest that local practice for monitoring of the pancreas allograft is followed (Not graded)
MONITORING OF HIV VIROLOGICAL CONTROL
Recommendations
We recommend that quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months thereafter (1B)
We suggest that more frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
We recommend that if patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR
Recommendations
We recommend that patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
We suggest that potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
We recommend that patients with HIV infection are unsuitable to be living kidney donors (1D)
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Recommendations:
We recommend that transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
– HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
– Information about the donor virus such as historical genotype patterns where possible and current viral load
– No history of virological failure or drug resistance (1D)
We recommend that recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
We suggest that HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
We recommend that patients with HIV-infection are unsuitable to be living kidney donors (1D)
Indications for kidney transplantation According to the BTS giudline no contraindication for transplant for HIV positive recepeint .
These patient need to be on HAARt treatment with cd4 count of more than 200 and undetectable HIV RNA .
HIV-positive patients are wait-listed only if– They are concordant with treatment, particularly cART therapy CD4+ T cell counts are >100 cells/µL.
General assessment ; these people need to ahve genarl assessment like Screening for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii Test for latent Mycobacterium tuberculosis infection with IGRA Treat TB as per NICE guidance Hepatitis B surface antigen or hepatitis C antibody positive should be investigated for the presence of liver cirrhosis Rule out cervical and/or anal neoplasia..
THese patient suppose to haver the prober HAART therapy and better to avoid PI regiem as it may lead to HIV resistance and drug -drug interaction .
Pre transplant we need to have an idea about the status of HIV resistance if any .
Cnotranindication for transplantation; Positive CDC crossmatch Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer ,Pregnancy. Multi-drug resistant HIV infection that cannot be controlled with currently available ART
INDUCTION AND IS better to induce induction through BASILIXMIAB AND AVOID ATG. try to use the IS and regular monitor for the interaction between HAART therapy and CNI.as it will affect the level under the curve irrespect to the trough level ,and this is could be the cause of rejection .
Still we go for HIV + donor for HIV +recipent :
the donor with good general health and imnmunity and CD4 of more than 200
Information about the donor virus such as historical genotype patterns where possible and current viral load No history of virological failure or drug resistance Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation Patients with HIV-infection are unsuitable to be living kidney donors
Kidney & Pancreas Transplantation in Patients with HIV Indications for Kidney transplantation Recommendations All potential kidney transplant recipients are screened for HIV infection HIV per se is not a contraindication for kidney transplantation HIV-positive patients are wait-listed only if– They are concordant with treatment, particularly cART therapy CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months HIV RNA has been undetectable during the previous 6 months No opportunistic infections have occurred during the previous 6 months No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
Suggestions The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV sppecialist
Indications for Pancreas Transplantation Recommendations Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) Contraindications to transplantation Uncontrolled HIV infection (CD4+ T cell levels persistently Habitual and irremediable non-concordance Multi-drug resistant HIV infection that cannot be controlled with currently available ART Positive CDC crossmatch Serious ongoing or recurring infection Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer ,Pregnancy General assessment All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile Patients with HIV RNA levels >200 copies /ml are suitable for SOT Screening for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii Test for latent Mycobacterium tuberculosis infection with IGRA Treat TB as per NICE guidance Hepatitis B surface antigen or hepatitis C antibody positive should be investigated for the presence of liver cirrhosis Rule out cervical and/or anal neoplasia
Suggestions SOT may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL Avoid nephrotoxic antivirals Avoid ritonavir and cobicista as drug interaction with CNI Scrren for Strongyloides stercoralis
Pre-transplant immunisation Hepatitis B virus (HBV) vaccine Influenza vaccine Diphtheria, tetanus and pertussis (DTP) vaccine Measles, mumps and rubella Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition
Induction and maintenance immunosuppression HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) and triple therapy maintenance immunosuppression including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent
Post-transplant prophylaxis Pneumocystis pneumonia Prophylaxis against cytomegalovirus – 3 months Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent
Monitoring Follow local practice Monitoring of HIV virological control
Use of HIV-infected donors for HIV-infected recipients If- HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury Information about the donor virus such as historical genotype patterns where possible and current viral load No history of virological failure or drug resistance Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation Patients with HIV-infection are unsuitable to be living kidney donors
I. Kidney & Pancreas Transplantation in Patients with HIV Summarise this article
Indications for kidney transplantation
– screen all potential kidney transplant recipients for HIV infection
– HIV is not a contraindication for kidney transplantation
– pre-transplant requirements include: adherence to HAART, CD4 >100 (ideally >200), stable CD4 for the last 3months, undetectable viral load for the last 6months, no OIs in the last 6months, no history of PML, chronic intestinal cryptosporidiosis or lymphoma
– decide on the most appropriate HAART before transplantation bearing in mind the potential drug-drug interactions
Indications for kidney transplantation
– consider diabetes patients in ESKD with controlled HIV infection for simultaneous kidney and pancreas transplantation
– consider solitary pancreas or islet transplantation in diabetic patients with severe hypoglycemic unawareness with well controlled HIV and stable kidney function (eGFR >40)
Absolute contraindications to kidney transplantation in HIV positive patients
– uncontrolled HIV infection i.e., CD4 <100 in the last 6 months, persistently detectable viralload in the last 3 months
– major psychiatric disease, irresolvable psychosocial problems, persistent substance abuse
– multidrug resistant HIV infection which cannot be controlled with the currently available HAART
– positive CDC crossmatch
– serious ongoing or recurring infection, including documented history of PML
– active malignancy on treatment, metastatic cancer, disseminated or untreated cancer
– pregnancy
Relative contraindications to kidney transplantation in HIV positive patients
– positive flow cytometric crossmatch (FCXM)
– ABO incompatibility
– treated malignancy including extracutaneous kaposi sarcoma
– severe and/ or uncontrolled medical problems which are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy
– chronic liver disease
– BMI >35
– HTLV infection
General assessment
– for all potential HIV positive transplant recipients, follow the existing guidelines on evaluation, selection and preparation of the potential transplant recipient
HIV specific assessment
– all potential transplant recipients should undergo a thorough immune-virological and antiretroviral status review i.e., review the CD4 count, HIV RNA level (viral load), current and previous
HAART regimens, HLA-B5701 status, HIV resistance profile
– patients with HIV RNA levels <200 copies/ml , otherwise well and adherent to their medications can be considered for SOT
– test transplant candidates for LTBI using IGRA ± mantoux test
– rule out active TB disease in transplant candidates who test positive for LTBI
– if there is evidence for active TB disease, treat the transplant candidates as per the guidelines
– if active TB has been ruled out, treat the transplant candidate for LTBI as per the guidelines
– screen all transplant candidates for viral hepatitis i.e., HBV and HCV
– if HBsAg or HCV Ab positive, the HBV DNA and HCV RNA levels should be quantified and be investigated for in the presence of liver cirrhosis
– all HBsAg positive potential transplant recipients on the waiting list for SOT should receive treatment to ensure HBV DNA is fully suppressed
– assess for presence of cervical and/ or anal neoplasia, treat those with advanced cervical/ anal intraepithelial neoplasia (CIN/ AIN III) or carcinoma in situ (CIS) prior to SOT
– do not offer kidney and/ or pancreas transplantation in patients with liver cirrhosis and in those with evidence of active HCV replication
– do not offer SOT in patients with HHV8-related primary effusion lymphoma or EBV-related lymphoma
– in selected cases, SOT may be appropriate for patients with fully suppressed HIV RNA and a CD4 <200 but >100
– in kidney transplantation, avoid HAART with nephrotoxic potential e.g., TDF, atazanavir if suitable alternatives are available
– in SOT, avoid HAART with significant drug-drug interactions with CNIs (e.g., ritonavir, cobicistat) if suitable alternatives are available
– screen for strongyloides stercoralis prior to transplantation in transplant candidates from endemic areas
– routine antiviral prophylaxis against HBV reactivation is not required in anti-HBc positive “alone” recipients (donor negative recipient HBsAg and HBV DNA negative) but for patients with increased risk of reactivation e..g., those on lymphodepleting therapy, antiviral prophylaxis can be given
Pancreas-specific assessment this entails:
– diabetic assessment for hypoglycemia unawareness, peripheral
neuropathy, autonomic neuropathy
– vascular assessment via ultrasound for limb vessels, consider non-contrast CT of the aorta and iliacs
– extensive cardiac assessment
Pretransplant immunization
– HBV vaccine should be administered to all non-immune patients (HBsAb titres <10mIU/mL)
– HAV vaccine is administered to all non-immune patients
– PPV-23 is administered to all patients
– VZV vaccine is administered to non-immune patients with CD4 >200
– Influenza vaccine is administered annually to patients awaiting SOT
– DTP vaccine is administered to all patients
– MMR vaccine is administered to all patients who are nonimmune to measles
– HPV vaccine is offered to patients at risk of HPV acquisition
Consideration of drug-drug interactions
– continue HAART in the perioperative period post-transplantation
– review the full and current medication list bi-annually and every time a therapeutic decision is made
– carry out a dose-finding trial of CNIs prior to SOT so as to determine the optimum doses to initiate post-transplant
– minimize drug-drug interactions by pre-emptively switching from boosted PI-based HAART regimens if alternatives are available
Induction and maintenance immunosuppression
– all HIV positive potential kidney transplant recipients should be offered induction therapy during transplantation
– interleukin-2 receptor antagonist (IL-2RA) is offered as induction therapy for most HIV-positive patients
– triple therapy maintenance immunosuppression (CNI, antiproliferative agent, steroids) is started at the time of kidney transplantation in HIV-positive patients
– manage acute rejection in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients
Post-transplant prophylaxis
– in HIV-positive transplant recipients, offer life-long prophylaxis against PCP following transplantation
– offer CMV prophylaxis in CMV seronegative recipients of organs from seropositive donors for a minimum of 3 months
– CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months
– assess transplant patients who are well and were not assessed and treated for LTBI or active disease prior to transplant
– those who were assessed prior to transplantation do not need reassessment for LTBI unless there is a new history of exposure to TB
– offer lifelong toxoplasmosis prophylaxis to toxoplasma IgG seropositive recipients with a CD4 <200 and any recipient of an organ from a seropositive donor
– there is no need for further testing beyond symptom review and CXR in patients with a reliable history of treated TB infection, such patients do not require TB prophylaxis unless TB re-exposure is suspected
– offer prophylaxis against MAC when CD4 is <50, stop once CD4 is >100 for 6 months
Monitoring allograft function
– regarding post-operative care of the HIV-positive kidney transplant recipient, follow the existing guidelines
– for pancreas allograft monitoring, follow the local practice
Monitoring HIV virological control
– monitor HIV RNA levels and CD4 at 1-month post-transplant, then every 2-3 months for the 1st year then every 3-6 months thereafter
– for patients with persistent HIV viremia, drug resistance testing is done to determine the treatment options
– consider more frequent CD4 count monitoring in patients receiving depleting antibodies so as to determine the need for anti-infective prophylaxis
Choice of living versus deceased donor
– HIV-positive patients have the same access to living donor kidney transplantation as non-infected patients
– HIV-positive individuals are not suitable living kidney donors (1D)
– potential donors for HIV-positive patients should be informed about the medical, surgical and psychosocial factors that may enhance the recipient’s morbidity and mortality risk, however disclosure of the recipient’s HIV status is not mandatory (not graded)
Consent and confidentiality
– for all transplantation involving HIV-positive patients, follow the existing guidelines on the ethics of deceased and living donor transplantation
– the standard of consent for HIV-positive transplant candidates is the same as for any other transplant
– the recipient is encouraged to disclose their HIV status to their donor wherever possible (not graded)
– ask the living donor whether there are any medical conditions that would make them change their decision to donate without highlighting HIV (not graded)
– living donors should be made aware that there are medical and social information regading the donor that has not been disclosed
– living donors should acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant
Use of HIV-infected donors for HIV-infected recipients
– transplantation using HIV-positive organs is restricted to organs from deceased donors with: –
HIV viral load <50 copies/ mL and CD4 >200 for at least 6 months prior to brain injury
information about the donor virus e.g., historical genotype patterns where possible and the current viral load
no history of virological failure or drug resistance
– recipients should be counseled and give informed consent both at the time of listing and during transplantation
– HIV-positive individuals are unsuitable to be living kidney donors (1D)
– restrict HIV-positive organ use to centers that have experience in transplanting HIV-positive patients
Summary: Indications for Kidney transplantation
Recommendations are:
· All potential kidney transplant recipients are screened for HIV infection
· HIV per se is not a contraindication for kidney transplantation
· HIV-positive patients are wait-listed only if: a) They are concordant with treatment, particularly cART therapy (1D) b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months c) HIV RNA has been undetectable during the previous 6 months d) No opportunistic infections have occurred during the previous 6 months e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
· The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication Indications for Pancreas Transplantation Recommendations are:
· Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation
· Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation
· Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) Contraindications to transplantation
Recommendations are:
· The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently less than 100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART
d) Positive complement-dependent cytotoxic (CDC) crossmatch
e) Serious ongoing or recurring infection, including documented history of PML
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer g) Pregnancy
· The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM)
b) Blood-type incompatibility
c) Treated malignancy, including extracutaneous Kaposi sarcoma
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy
e) Chronic liver disease
f) Marked obesity (BMI >35 kg/m2 ) (2D) g) HTLV infection
General assessment
Recommendations are:
· Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease HIV-specific assessment
Recommendations are:
· All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile
· Patients with HIV RNA levels 200 cells/µL
· Influenza vaccine is administered annually to patients awaiting solid organ transplantation We suggest that: • Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients • Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles • Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition
· Consideration of drug-drug interaction recommendations are:
· Continuation of antiretroviral therapy in the perioperative period following transplantation
· A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point
· A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
· Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions
· HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
· Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
INDICATIONS FOR KIDNEY TRANSPLANTATION
All potential kidney transplant recipients are screened for HIV infection (1D) We recommend that HIV per se is not a contraindication for kidney transplantation (1B) We recommend wait-listing HIV patients only if: a) They are concordant with treatment, particularly cART therapy (1D) b) Their CD4+ T cell counts are >100 cells/µL (ideally >200 cells/µL) and have been stable during the previous 3 months (1B) c) HIV RNA has been undetectable during the previous 6 months (1B) d) No opportunistic infections have occurred during the previous 6 months (1B) e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
CONTRAINDICATIONS TO TRANSPLANTATION
The following are absolute contraindications to kidney transplantation in patients with HIV: a) Uncontrolled HIV infection (CD4+ T cell levels persistently 35 kg/m2 ) (2D) g) HTLV infection (1D) b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D) c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D) d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D) e) Serious ongoing or recurring infection, including documented history of PML (1D) f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D) g) Pregnancy (1D) We suggest that the following are relative contraindications to kidney transplantation: a) Positive flow cytometric crossmatch (FCXM) (1D) b) Blood-type incompatibility (2D) c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C) d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D) e) Chronic liver disease (2D) f) Marked obesity (BMI >35 kg/m2 ) (2D) g) HTLV infection (1D)
HIV-SPECIFIC ASSESSMENT
All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D) We suggest that in selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C) We recommend that patients with HIV RNA levels less than 200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
We suggest that antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded) We suggest that antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D) We recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D) We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C) We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection following the testing strategy for immunocompromised HIV infected patients in the current NICE Tuberculosis Guidelines (1C) We recommend that transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C) We recommend that transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C) We recommend that transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C) We suggest that transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D) We recommend that all transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and undergo investigation for the presence of liver cirrhosis (1C) We recommend that all hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B) We suggest that anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D) We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C) We recommend that patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D) 40 We recommend against solid organ transplantation in patients with a history of extracutaneous Kaposi sarcoma, Castleman’s disease, human herpes virus 8 (HHV8)- related primary effusion lymphoma or Epstein-Barr virus (EBV)-related lymphoma (1D)
PRE-TRANSPLANT IMMUNISATION
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres 200 cells/µL (1C) We suggest that: • Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D) • Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D) • Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C) We recommend that influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
CONSIDERATION OF DRUG-DRUG INTERACTIONS
A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded) We suggest a dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D) We suggest pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D) We recommend continuation of antiretroviral therapy in the perioperative period following transplantation (1D) We suggest that all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION
All HIV-positive patients eligible for kidney transplanoffered induction therapy at the time of transplantation (1C) We recommend that for the majority of HIV-positive patients induction theraan interleukin-2 receptor antagonist (IL-2RA) (1B) We recommend that HIV-positive patients are given triple therapy maimmunosuppression started at the time of kidney transplantation, includinga calcineurin inhibitor (CNI) and an anti-proliferative agent (1C) We suggest that acute rejection is treated in HIV-positive kidney transplant in the same way as HIV-negative kidney transplant recipients (2D)
POST-TRANSPLANT PROPHYLAXIS
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D) We suggest that Toxoplasma IgG seropositive recipients with a CD4+ count less than 200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C) We recommend that prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A) We recommend that CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A) Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C) Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C) Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C) We suggest that where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D) 68 We suggest that prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
MONITORING ALLOGRAFT FUNCTION
Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded) We suggest that local practice for monitoring of the pancreas allograft is followed (Not graded)
MONITORING OF HIV VIROLOGICAL CONTROL
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months thereafter (1B) We suggest that more frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D) We recommend that if patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
CONSENT AND CONFIDENTIALITY
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded) We recommend that the standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded) We suggest that, wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded) We suggest that all living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded) We suggest that all living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded) We suggest that all living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded) We recommend that transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded)
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with: – HIV viral load 200/µL for at least 6 months prior to brain injury – Information about the donor virus such as historical genotype patterns where possible and current viral load – No history of virological failure or drug resistance (1D) We recommend that recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D) We suggest that HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded) We recommend that patients with HIV-infection are unsuitable to be living kidney donors (1D)
The article deals with the British Transplantation society guidelines for kidney & pancreas transplantation in patients with HIV, published in 2015, and revised in January 2017.
Use of combination antiretroviral therapy (cART) has changed the prognosis of human immunodeficiency virus (HIV) infected patients. HIV associated nephropathy (HIVAN) is the commonest cause of end stage renal disease (ESRD) in HIV-positive patients. Survivla rates for patients are higher if they undergo a renal transplant rather than remaining on dialysis. cART use has made it possible to offer renal transplant to HIV-positive patients, if they fulfil the criteria laid down.
Indications for kidney transplantation: All potential kidney transplant recipients (KTRs) should be screened for HIV and if positive, they can be wait-listed provided they are concordant to treatment (especially cART), have undetectable HIV RNA for last 6 months, have stable and >100 cells/microL (ideally >200) level of CD4 counts for last 3 months, without any history of opportunistic infections in last 6 months, and no history of lymphoma, cryptosporidiosis, or progressive multifocal leukoencephalopathy (PML).
The most appropriate cART for the prospective KTR can be decided in conjunction with an HIV specialist keeping in mind the interactions with immunosuppressive medications required post-transplant (using integrase inhibitors which do not inhibit CYP450), to prevent rejections post-transplant.
Indications for Pancreas transplantation: Simultaneous pancreas and kidney transplant (SPK) should be considered for HIV-infected diabetics with renal failure. Solitary pancreas or islet transplantation should be offered to HIV-infected diabetics with severe hypoglycemic unawareness (despite best possible diabetic care), and having eGFR >40ml/min. Prospective HIV-positive pancreas transplant recipients should be assessed in a centre with such experience. The HIV-infection should be well controlled before proceeding with transplant.
Contraindications to kidney transplantation in HIV-positive patients: Absolute contraindications include pregnancy, a positive CDC crossmatch (no evidence to support safety of desensitization in HIV-positive patients), uncontrolled HIV infection (persistently detectable HIV RNA for last 3 months, and CD4 T cell </microL for last 6 months), ongoing or recurring infection (empyema, Aspergillus infection, methicillin resistant staphylococcus aureus, MRSA, vancomycin-resistant enterococcus, VRE, active cytomegalovirus, CMV, active tuberculosis, influenza virus, respiratory syncytial virus, RSV, PML), active malignancy under treatment, any metastasis or untreated cancer, multi-drug resistant HIV infection, or habitual non-adherence due to psychiatric disease, psychosocial problems or substance abuse. Patients with advanced cardiopulmonary disease are also excluded. Patients with chronic hepatitis B and C virus infection need further evaluation and, in presence of active hepatitis or cirrhosis, might not be candidate for transplantation.
Relative contraindications include a positive flowcytometry crossmatch, blood group incompatibility, treated malignancy (wait-period of 2-5 years recommended according to the malignancy type), BMI >35 (increased surgical complications), HTLV infection (risk of developing leukemia and myelopathy post-transplant), chronic liver disease (CLD), or severe medical problems not likely to improve post-transplant (like elderly patient with marked obesity, extensive smoking history, marked obesity and extensive cardiac disease).
General assessment: Existing guidelines for prospective KTR evaluation, selection, and preparation should be followed in HIV-positive patients.
HIV-specific assessment: Prospective transplant recipient should be evaluated with respect to history of antiretroviral therapy, HIV viral load, CD4 count, HLA-B5701 status, and HIV resistance profile. Assessment for infections and malignancies like syphilis, HSV (Herpes simplex virus), EBV (Epstein Barr virus), CMV (cytomegalovirus), VZV (varicella zoster virus), HTLV (human T-cell leukemia virus), Toxoplasma gondii, active tuberculosis, latent Tuberculosis, HBV, HCV, cervical and/or anal neoplasia evaluation should be done. Serological HBV or HCV positivity should be further evaluated with HBV DNA/ HCV RNA levels and for presence of liver cirrhosis. Anti-HBc positive ‘alone’ recipients, if given lymphodepleting agents, should be given antiviral prophylaxis. Active tuberculosis, HBV infection, HCV infection and cervical/ anal intraepithelial neoplasia or carcinoma in situ must be treated prior to transplant.
Patients with liver cirrhosis and active HCV replication or with history of Castleman’s disease, EBV related lymphoma, or Human herpes virus-8 (HHV-8) related primary effusion lymphoma should not be transplanted.
Appropriate cART regimen should be used, avoiding nephrotoxic drugs (tenofovir and atazanavir) and drugs having interactions with CNIs (ritonavir and cobicistat). In patients with low level viremia (HIV RNA <200 copies/ml), transplant can be considered after antiretroviral resistance test.
Pancreas-specific assessment: Transplant candidates should be counselled and informed regarding paucity of experience in this field, and the transplant should be performed in a centre having experience in performing pancreas transplants as well as transplants in HIV-infected patients. Assessment should include diabetic assessment (hypoglycemic awareness, autonomic neuropathy, and peripheral neuropathy), vascular assessment (peripheral vessels, aorta and iliac vessel assessment using ultrasound and CT), and cardiac assessment (ECG, myocardial perfusion scan or dobutamine stress echocardiography, and coronary angiography – in age >50, type 1 diabetes, ESRD for > 3 years, and significant cardiac history).
Pre-transplant immunization: The patient should be immunized with HBV vaccine (larger and more frequent doses may be required), Hepatitis A virus (HAV) vaccine (2 doses if CD$ >300, and 3 doses if CD4 <300), pneumococcal vaccine (for those with CD4>200, and for those with CD4<200 if associated CLD, CKD or DM), varicella zoster virus vaccine (for those with CD4>400), annual influenza vaccine (especially with CKD, CLD or DM), human papilloma virus vaccine (for at-risk patients), measles, mumps and rubella (MMR) vaccine (for those with CD4>200), and diphtheria, tetanus and pertussis (DTP) vaccine.
Consideration of drug-drug interactions: A dose-finding trial of CNIs pre-transplant can be done to detectthe optimal dose required post-transplant (to prevent rejections post-transplant due to inadequate CNI dose), especially in those on protease inhibitors. Pre-operative switching of ART from boosted protease inhibitors (which increase CNI and mTOR inhibitor drug levels) to alternative agents should be done. ART should be continued in post-transplant period. 6 monthly medication review should be done. HIV drug interaction resource should be used by physicians to find put any potential drug-interaction post-transplant. Both patients and clinicians should be aware of immunosuppressive drug timings, dosages, frequencies, concentrations, and interactions with other drugs.
Induction and maintenance immunosuppression: All patients should be offered induction therapy, with use of interleukin-2 receptor antagonist in majority of the patients. Evidence for use of lymphocyte-depleting agents and belatacept is insufficient to recommend their use. CNI, steroids, and anti-proliferative agent based triple drug maintenance immunosuppressive regime should be started at time of transplant (due to high rejection rates seen in HIV-infected patients). Treatment of acute rejection warrants the use of standard protocol (as for HIV-negative recipient).
Post-transplant prophylaxis: It would include prophylaxis against pneumocystis pneumonia (lifelong cotrimoxazole 480 mg, dapsone 100 mg daily, or aerosolized pentamidine 300 mg monthly), cytomegalovirus (minimum 3 months for CMV seronegative recipients of seropositive donor organ), toxoplasma (cotrimoxazole 960 mg daily lifelong, or dapsone 50 mg daily with pyrimethamine 50 mg weekly, in seropositive recipients with CD4 <200), and mycobacterium avium complex, MAC (with azithromycin 1250 mg weekly, clarithromycin 500 mg twice a day, or rifabutin 300 mg daily, if CD4 <50). Assessment for tuberculosis disease or latent TB infection should be done only if not done pre-transplant or in the event of re-exposure.
Post-transplant monitoring of allograft function: It should be done as per standard protocol followed for non-HIV-infected KTRs. For pancreas recipients, local practice should be followed in view of varying practices all over UK.
Monitoring of HIV virological load: Quantitative HIV RNA and CD4+ T cell count should be measured at 1 month, then every 2-3 month till 1 year, and then every 3-6 monthly. More frequent CD4 count monitoring in those receiving lymphocyte depleting agents. Drug resistance testing may be required in case of persistent viremia.
Choice of living versus deceased kidney donor: HIV-infected patients should have same access to living donor transplantation as that of HIV-noninfected patients. HIV-infected patients are not suitable for living kidney donation due to increased risk of kidney disease in them. The medical, surgical, and psychosocial factors of the recipient should be informed to the donor, but the disclosure of recipient HIV status is not mandatory.
Consent and confidentiality: Existing guidelines on ethics and standard consent protocol should be followed in all patients. The recipient is encouraged to disclose their HIV status to the prospective donor. All living donor should be aware and acknowledge that complete medical and social information of the recipient which is not relevant to the kidney transplant outcome might not be provided to them and should be asked if presence of any medical condition in the recipient would lead to change in their decision to donate.
Use of HIV-infected donors for HIV-infected recipients: Deceased donors with HIV ciral load <50 copies/ml and CD4 count >200 for minimum 6 months prior to brain injury, with no history of virological failure or drug resistance can be transplanted to HIV-positive recipients after counselling (regarding risk of transmission of drug resistance and opportunistic infections, as well as risk of HIV-associated nephropathy in the donor organ) and written informed consent. HIV/HCV con-infected donor organ should not be used. HIV positive organ use for transplantation should be done only in centres experienced in transplanting HV-positive patients. HIV-infected patients are not suitable for living kidney donation due to increased risk of kidney disease in them.
I. Kidney & Pancreas Transplantation in Patients with HIV Indications for Kidney transplantation
· All potential kidney transplant recipients are screened for HIV infection (1D)
· HIV per se is not a contraindication for kidney transplantation (1B)
· HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
· The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist.
Indications for Pancreas Transplantation
· Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation
· Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
· Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min)
Contraindications to transplantation
· The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during
the last 6 months and HIV RNA persistently detectable during the last 3 months)
(1C)
b) Habitual and irremediable non-concordance ( mostly due to severe psychiatric illness) (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available
ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, (history of PML) (1D)
f) Active malignancy, metastasis, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
· The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2 ) (2D)
g) HTLV infection (1D)
General assessment
· Existing guidelines regarding evaluation, selection and preparation of the candidates are followed for all candidates with HIV disease
HIV-specific assessment
· All transplant candidates undergo careful immuno-virological and antiretroviral status review. (1D)
· Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
· Transplant candidates undergo serologic testing for syphilis, HSV, EBV, CMV, VZV, human T-cell leukemia, and Toxoplasma gondii (1D)
· Transplant candidates are tested for LTBI with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
· Transplant candidates who test positive for LTBI are assessed for any evidence of active tuberculosis disease (1C)
· Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
· Transplant candidates with LTBI, in whom active disease has been excluded are treated for LTBI, according to current NICE TB guidelines, prior to transplantation (1C)
· All transplant candidates are screened for viral hepatitis. Those found to be HBsAg or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
· All HBsAg (+) patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
· Patients considered for SOT are assessed for the presence of cervical and/or anal neoplasia; those with advanced stage be treated before transplantation (1D)
· Kidney and/or pancreas transplantation is not recommended in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
· SOT is not recommended in patients with a history of Castleman’s disease, (HHV8)-related primary effusion lymphoma or (EBV)- related lymphoma (1D)
· In selected cases, SOT may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
· Nephrotoxic Antiretrovirals (tenofovir, atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available.
· Antiretrovirals with significant drug-drug interactions with CNI (ritonavir and cobicistat) are avoided in the setting of SOT if suitable alternatives are available (2D)
· Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
· Anti-HBc positive “alone” recipients do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (2D)
Pancreas-specific assessment
· Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C)
· Transplant candidates are carefully counseled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients.
· Pancreas transplantation assessment in patients with HIV includes:
a) Diabetic assessment b) Vascular assessment c) Extensive cardiac assessment (2C)
Pre-transplant immunization
· HBV vaccine is administered to all non-immune patients (HBs antibody titers <10 mIU/mL) (1B) • Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D) • Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B) • Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
· Influenza vaccine is administered annually to patients awaiting SOT (1B)
· Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
· MMR vaccine is administered to all patients who are nonimmune to measles (2D)
· Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
Consideration of drug-drug interactions
· Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
· A full and current medication review as part of the assessment for SOT, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point.
· A dose-finding trial of CNIs prior to SOT in order to determine optimum doses to initiate post-transplant (2D)
· Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
· That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (http://www.hiv-druginteractions.org)
Induction and maintenance immunosuppression
· All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
· For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
· HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a CNI, and an anti-proliferative agent (1C)
· Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
· HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
· Prophylaxis against CMV is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
· CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
· Transplant patients who are well and were not assessed and treated for LTBI or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
· Transplant patients who are well and were assessed and treated for LTBI or disease before transplantation do not need re-assessment for LTBI unless there is a new history of exposure to TB (1C)
· Transplant patients who are re-exposed to TB after transplantation should be assessed for LTBI and/or disease as recommended in current NICE TB guidance on TB contact tracing (1C)
· Toxoplasma IgG (+) recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor (+) for toxoplasmosis receive lifelong prophylaxis (2C)
· Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
· Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
Monitoring allograft function
· Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease.
· Local practice for monitoring of the pancreas allograft is followed.
Monitoring of HIV virological control
· Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
· If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
· More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living versus deceased donor
· Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
· Patients with HIV infection are unsuitable to be living kidney donors (1D)
· Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory.
Consent and confidentiality
· Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease.
· The standard of consent for HIV-positive transplant candidates is the same as for any other transplant.
· Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance.
· Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor
· All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV
· All living donors are made aware that there may be medical and social information about the recipient that is not disclosed.
· All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant
Use of HIV-infected donors for HIV-infected recipients
· Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
b) Information about the donor virus (genotype and current viral load)
c) No history of virological failure or drug resistance (1D)
· Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
· Patients with HIV-infection are unsuitable to be living kidney donors (1D)
· HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients
Summary Prerequisite for Kidney transplantation
• All recipient should be screened for HIV infection (1D)
• HIV-positive patients can be kept in wait-listed only if:
a) On cART therapy (1D)
b) CD4+ T cell counts >100 cells/µL (ideally > 200 cells/ µL) for 3 months (1B)
c) HIV RNA undetectable during the previous 6 months (1B)
d) No opportunistic infections during the previous 6 months (1B)
e) No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Indications for Pancreas Transplantation
• Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
• Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded)
Contraindications to transplantation
a) Standard contraindication of renal transplant
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
g) Pregnancy (1D)
Relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2 ) (2D)
g) HTLV infection (1D)
Vaccination
Need to take following vaccination.
• Influenza vaccine (1B)
• Diphtheria, tetanus and pertussis (DTP) (2D)
• Measles, mumps and rubella (MMR) (2D)
• Human papilloma virus (HPV)(2C)
Drugs
Monitor drug-drug interactions.
• A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
• Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens,in order to minimise drug interactions (2D)
Induction Therapy
• Are offered induction therapy at the time of transplantation (1C)
• For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• Maintenance immunosuppression with triple therapy started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
• Acute rejection is treated in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
• Need lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
• Cytomegalovirus prophylaxis for a minimum of 3 months (1A)
• CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
• Need mycobacterium tuberculosis latent infection or disease treatment before transplantation (1C)
•Prophylaxis for Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
• Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL(2D)
Monitoring allograft function
• Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
• If HIV viraemia persistent, drug-resistance testing is carried out (1D)
• More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies (2D)
Choice of living versus deceased donor
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D)
• Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality
• Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
• All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
• HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
SPK IN HIV RECIPIENT
HIV is not a contraindication for transplantation
indication of KT
All potential kidney transplant recipients are screened for HIV infection (1D)
• HIV per se is not a contraindication for kidney transplantation (1B)
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been
stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma
CONTRAINDICATION TO KT
Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during
the last 6 months and HIV RNA persistently detectable during the last 3 months)
(1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric
disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available
ART (1D)
SCREENING
Transplant candidates undergo serologic testing for syphilis, herpes simplex virus,
Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus
and Toxoplasma gondii
LTBI
KT not advised in case of liver cirrhosis and lymphoma associated with HHSV8 and EBV
Pancrea transplant should be done in centre regular with HIV recioients and also pancreas transplant BOTH
IMMUNIZATION
HBVB HAV , VZV, PNEIUMOCOCCAL, INFLUENZA, vaccins shold be given
INDUCTION IS
induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
triple therapy maintenance immunosuppression can be given
Post-transplant prophylaxis
Life long PJP prophylaxis
CMV prophylaxis in D+/R-
Treat if LTBI diagnosed
HIV monitoring
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first
assays at 1 month after transplant and subsequent studies every 2-3 months for the first
year then every 3-6 months thereafter (1B)
• If patients have persistent HIV viraemia, drug-resistance testing is carried out to
determine treatment options (1D)
Choice of living versus deceased donor
Access to Live donor is same like non HIV
HIV donor is unsuitable for live donation
CONSENT
general rules applies here
Recipient is SUGGESTED to disclose HIV status to donor
Use of HIV-infected donors for HIV-infected recipients
DONORS with following parameters CAN DONATE
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to
brain injury
b) Information about the donor virus such as historical genotype patterns where
possible and current viral load
c) No history of virological failure or drug resistance (1D)
Summary Background
HIVAN is the most severe form of CKD and commonest cause of ESRD in HIV positive patients in UK.
Patients with HIVAN are usually young (median age of 36 years) with severe immunodeficiency and with advanced CKD at time of diagnosis.
HAART may retard the progression but most patients will progress to ESRD within 10 years from time of diagnosis.
Kidney transplantation prior to the era of cART was disappointing with patient median survival of 4 years.
Antiretroviral treatment has made kidney transplantation in HIV positive patients feasible.
However it is complicated with high rates of acute allograft rejection which could be attributed due to lack of balance between immunosuppression and viral suppression.
The use of cART is associated with metabolic syndrome and diabetes mellitus.
Indications for kidney transplantation
Kidney transplantation in HIV patients with ESRD is associated with better survival rates than patients who remain on dialysis.
Studies have shown that in the carefully selected HIV positive patient patient survival and graft outcomes at 1 and 3 years are similar to the non-HIV population.
The following criteria should be met:
Good adherence to cART
CD 4 counts <200 >100 cells/iu for last 3 months
HIV RNA undetectable for last 3 months
No opportunistic infection in the last 6 months
No prior history of PML, lymphoma, chronic intestinal cryptosporidiasis.
All potential kidney transplant recipients should be screened for HIV.
HIV is not a contraindication for transplantation.
Indication for pancreas transplantation
DM patients with controlled HIV infection in ESRD should be considered for simultaneous kidney- pancreas transplant.
Diabetic patients with severe hypoglycaemic awareness with stable HIV and kidney function should be considered for pancreas transplantation.
Contraindications to transplantation Absolute contraindications
1. Uncontrolled HIV infection low CD 4 counts and detectable HIV viral load
2. Non-compliance to cART either due to psychiatry illness, psychosocial factors or substance abuse.
3. Multi drug resistance HIV with no available cART.
4. Positive CDC crossmatch.
5. Serious ongoing infections including documented history of PML.
6. Pregnancy
7. Active malignancy
HIV specific assessment
1. All transplant recipients to due immunological and virological evaluation that includes CD4 counts, HIV RNA, prior cART AND HIV resistance profile. Ideally the CD4 counts should be >200cells/ul (liver transplantation>100 cells/ul) with undetectable HIV RNA, however in carefully selected patients a detectable HIV RNA/CD<200cells/ul may be accepted.
2. Antiretrovirals that are nephrotoxic or those with significant drug interactions with immunosuppression should be avoided.
3. Recipients should undergo testing for latent TB with IGRA and those with positive test treated prior to transplantation.
4. Recipients should undergo screening for syphillis, HSV,VZV,CMV,EBV,HTLV, HBV, HCV, toxoplasmosis and strongyloides stercolaris in endemic areas.
Pre-transplant immunisation
All non-immunised patients should receive Hepatitis B, Hepatitis A and VZV vaccination if CD4 count>200cells/ul.
MMR can be offered to non-immunised patients
HPV should be offered to those at risk of acquisition.
Influenza should be given annually on all on the waiting list.
All patients should receive pneumococcal and DTP vaccine.
Patients who had received DTP >10 years prior should receive a booster.
Pneumococcal should be repeated every 3-5 years.
Consideration of drug-drug interaction
Pre-emptive switching from PI in order to minimise drug interactions.
PIs inhibit the p-glycoprotein transport and the CYP450 leading to increased levels of CNIs and mTOR inhibitors.
NNRTIs are inducers of CYP450 leading to slight decrease of CNIs and mTOR inhibitors.
Integrase inhibitors have minimal interaction with immunosuppressive therapy.
Continuation of cART during the peri-operative period.
Full and current medical review to be carried out twice yearly and after every therapeutic decision point.
Induction and maintenance therapy.
The recommended induction therapy is IL2RA .
Evidence of lymphocyte depleting agents in HIV is limited. They are associated increased infections and malignancy in the non-HIV population thus not recommended in the HIV population.
Maintenance therapy should be triple therapy.
There is insufficient data to recommend the best maintenance therapy, however due to high rates of rejection the effective combination is steroids+ mycophenolate+ tacrolimus.
Acute rejection in HIV positive should be managed was the same way as HIV negative.
Post-transplant prophylaxis.
PCP prophylaxis should be offered lifelong.
The recommended drug is cotrimoxazole 480mg OD.
Toxoplasmosis prophylaxis should be offered to seropositive patient with CD4 <200cells/ul or a recipients who received from seropositive donor for lifelong.
The recommended drug is cotrimoxazole 960mg OD
CMV prophylaxis should be offered for D+/R-
The recommended drug is valganciclovir.
MAC prophylaxis should be offered to patients with CD4 counts<50cells/ul.
Recommended drugs is azithromycin.
Monitoring allograft function
Post-operative care for HIV positive kidney transplant recipients would be similar to non-HIV.
Monitoring HIV virological control
HIV RNA and CD4 counts should be monitored regularly with first assay at first month then ever 2-3 months in the first year then every 3-6 months thereafter.
Patients who received antibodies depleting agents will require more frequent monitoring.
If HIV viremia persists the patient should be tested for resistance.
Choice of living versus deceased donor
HIV infected patients should have same access to living donation as non-HIV.
Donors should be informed of factors that may heighten recipients morbidity and mortality risk, however disclosure of recipient HIV status is not mandatory.
HIV infected donors are unsuitable as living kidney donors.
Consent and confidentiality
Existing ethics guidelines for deceased and living donors should be followed.
Standard consent for HIV patients is similar to non-HIV patients.
Recipients is encouraged to disclose their status to donor.
Donors should be asked if there are any medical conditions that would make them change their decision to donate.
Living donors should be made aware that there is some information on medical and social factor on the recipient that will not be disclosed to them.
Summary of BTS guideline for kidney and pancreas transplantation in HIV infection
Introduction
Kidney transplantation in HIV-positive ESRD patients is considered the standard of care for the last 15 years with improved life expectancy due to the effective use of C ART since 1996 increased number of patients offered kidney transplantation with specific consideration and an increased number of centers offered transplantation and this guideline revised from the previous copy in 2016 based on the available current evidence this guideline will give a comprehensive summary of kidney and pancreas transplantation in this specific group of patients
transplantation in HIV-infected patients can be offered provided they fit the following eligibility criteria
1. Medically fit and life expectancy > 5 years, stable on ART for the last 3 months
2. Negative viral load < 50 copies for the last 6 months of FU with HIV specialist
3. Responsive to ART and no previous poor compliance or resistance to the therapy
4.CD4 count > 100 preferred above 200 cells /ml
5.No active infection for 6 months including opportunistic infection
6.No evidence of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Also suggested discussing with the patient and the HIV specialist the choice of ART before transplantation to avoid drug-drug interaction, especially with CNI and everolimus. Indications for Pancreas Transplantation Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Diabetic patients with severe hypoglycemia unawareness may offer solitary pancreas transplantation or islet transplantation if they have well-controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) absolute contraindication for kidney transplantation in HIV patients . Active HIV disease with persistent viremia despite C ART
. Low CD4 count < 100 cell/ml for the last 6 months
. Active substance abuse and major psychiatric illness
. Multiple ART resistance
. Positive CDC crossmatch
. Active infection including active TB treatment
. Active malignancy on treatment, or disseminated tumor
. pregnancy
Relative contraindications to kidney transplantation:
1. Positive flow cytometric crossmatch (FCXM) (1D)
2. Blood-type incompatibility (2D)
3. Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
4. Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
5. Chronic liver disease (2D)
6.Marked obesity (BMI >35 kg/m2) (2D)
7. HTLV infection (1D) HIV-specific assessment 1 Specific immunovirological screens like CD4 count, HIV RNA viral load
2. Review the drug history including the ART dosing duration any previous intolerance, side effect, or resistance
3. serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human T-cell leukemia virus
and Toxoplasma gondii (1D)
4. screen for LTBI or ACTIVE TB and treat accordingly to insure eradication of active TB.
5. All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA /
hepatitis C RNA levels quantified and investigated for the presence of liver cirrhosis
6. HBV screen with HBs Ag positive should be tested for hepatitis B DNA (1B)
7. all HIV positive candidates need to be assessed for the presence of
cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial
neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to
transplantation (1D
8. Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those
with evidence of active HCV replication (1C)
9. patients with a history of Castleman’s disease, human
herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)-
related lymphoma (1D)
10. Transplant candidates from endemic regions are screened for Strongyloidiasis stercoralis infection prior to transplantation (2D)
11.avoid nephrotoxic ART and ART with PI activity due to drug-drug interaction with other IS
For pancreas transplant further assessment
First, discuss with the patient that needs to be assessed in care with good experience in kidney transplant and should be informed about the limited experience for pancreas transplantation in a such specific group of patients
1. Diabetic assessment (for hypoglycemic unawareness, peripheral neuropathy, &
autonomic neuropathy)
b) Vascular assessment (ultrasound assessment of leg vessels, and consider non-contrast CT of the aorta and iliac arteries), risk of vascular thrombosis
c) Consideration of a more extensive cardiac assessment (2C) vaccination prior to transplantation
1. HBV vaccination for those with HBS ab < 10 iu
2. HAV vaccination
3. Pnemovax 23 for all non-immune
4.Seasonal influenza vaccine (annual)
5.Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
We suggest also Diphtheria, tetanus, and pertussis (DTP) vaccine is administered to all patients (2D)
• Measles, mumps, and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D)
• Human papillomavirus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C).
Induction and maintenance IS for HIV recipients
Induction therapy is preferred with an interleukin-2
receptor antagonist (IL-2RA)
Maintenance
triple immunosuppression steroids, a calcineurin inhibitor (CNI) and
an anti-proliferative agent (1C)
• Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant chemoprophylaxis
1, life -long for PJP
2. CMV D +VE /R+ve prophylaxis for minimum 3 months (1A).
3. CMV seropositive transplant recipients receive either prophylaxis against CMV infection
or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A).
4. patient with a previous history of LTBI or previous history of treated active TB should be assessed for latent reactivation after a history of exposure post-TX and follow the same NCE GUIDLIEN for latent TB treatment
5. Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong
prophylaxis (2C)
6. Previously treated TB infection no need for TB prophylaxis or reassessment unless there is a suspected risk of re-exposure
7. Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6
months (2D).
post-transplantation HIV viral load monitoring
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays 1 month, and subsequent studies every 2-3 months for the first year and then every 3-6 months thereafter (1B) • If patients have persistent HIV viremia, drug-resistance testing is carried out to determine treatment options (1D
Kidney and pancreas transplantation in patients with HIV
Guidelines advised by British society for transplantation, aiming to cover all aspects of assessment, selection and management of people living with HIV recipients.
Indication for kidney transplantation
Recommendations
· Screen all Kidney transplant recipients for HIV (1D)
· HIV is not a contra indication for KT (1B)
· Waist list if ;
§ On ART (1D)
§ CD 4 cell > 200cells/microL(1B)
§ Undetectable HIV RNA foe last 6 months (1B)
§ NO opportunistic infection in last 6 months (1B)
§ No PML, Intestinal cyptosporidosis or lymphoma(1B)
Suggestion
· ART to be discussed before transplantation(Not graded)
Indications for Pancreas Transplantation
Recommendations · Pancreas recipients should be assessed in center experience in KT for HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded)
Suggestions
· Diabetics with controlled HIV infection can be considered for,
· Simultaneous KPT(2D)
· If they have severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if kidney function is stable. (Not graded) Contraindication to transplantation
· Absolute contraindication to kidney transplantation in patients with HIV 1. Uncontrolled HIV infection CD4< 100cell/ul(1C)
2. No adherence to treatment (1D)
3. Resistance to available ART drugs (1D)
4. Positive CDC cross match(1D)
5. Serious ongoing/recurrent infection/PML (1D) 6. Active/ disseminated malignancy(1D) 7. Pregnancy
· Relative contraindications to kidney transplantation in patients with HIV
· Evaluate virological and ART status (1D)
· If HIV RNA <200 copies/mL, considered Transplant if adherent with medications (1C)
· Serology for syphilis, HSV, EBV, CMV, VZV, HTCLV, Toxoplasma and Strongyloides (1D)
· TB screening & treatment prior to transplant (active/ Latent) with IGRA +/- TST (1C)
· Screened for viral hepatitis; If serology positive to confirm with DNA/RNA and to look for cirrhosis (1C)
· HBsAg positive patients to receive treatment and ensure viral suppression (1B)
· Screen & treat for cervical and/or anal neoplasia (1D)
· SOT can be considered in case HIV RNA suppressed & CD4 < 200 but >100 cells (2C)
· Avoid antiretroviral with nephrotoxic potential or drug-drug interactions.
· Anti-HBc positive “alone” recipients do not require prophylaxis unless reactivation risk is high.
Pancreas-specific assessment
Should be performed in experience center with HIV patients.
• Pancreas Transplant assessment in patients with HIV includes:
• Detailed diabetic assessment, vascular assessment& cardiac assessment (2C)
Pre-transplant immunization
Recommendation
• HBV vaccination of all patients if titer <10 mIU/mL (1B)
• HAV vaccine (for non-immune) (1D)
• PPV-23 (1B)
• VZV vaccine (non-immune) with CD4 >200 cells/μL (1C)
• Influenza vaccine annually (1B)
Suggestion
• DTP to all patients (2D)
• MMR to none immune Patients (2D)
• HPV for high risk (2C)
Consideration of drug-drug interactions Recommendation
• To consider ART in the perioperative period (1D) Suggestions
• Medication review as part of the assessment (Not graded)
• CNI trials to determine optimum doses (2D)
• Switching from PI regimens to minimize drug interactions (2D)
Induction and maintenance immunosuppression Recommendation
• Induction therapy offered to All KTR with HIV-positive at time of Tx1C)
• Induction therapy is with IL-2RA (1B)
• Triple maintenance IS started at the time of kidney transplantation (1c) Suggestion
• Acute rejection is treated the same way as HIV-negative KTR (2D)
Post-transplant prophylaxis Recommendation
• Lifelong prophylaxis against PCP (1D)
• CMV prophylaxis; if CMV R-/ D+ for of 3 months (1A)
• Recipient CMV positive; either prophylaxis or surveillance and pre-emptive therapy for 3 months (1A)
• Assess and treat LTBI prior to transplantation, revaluate if new exposure history or symptoms develop, and treat as per NICE guidelines (1C) Suggestion
• Toxoplasma lifelong prophylaxis if either donor is positive or recipient positive & CD4 <200 (2C)
• MAC prophylaxis; if CD4 count ≤ 50. To be stopped when the count is >100 cells/μL for 6months (2D)
Monitoring allograft function Recommendation
• Follow the current guidelines for post-operative care of the KTR (Not graded)
Monitoring HIV virological control Recommendation
• HIV RNA and CD4+ T-cell counts, at 1 month then 2-3 months for the first year then every 3-6 months (1B), more frequent if receiving antibody depleting to assess the need for prophylaxis (2D)
• If Viremia is persistent test for drug-resistance (1D)
Choice of living versus deceased donor Recommendation
• Access to living donor KT should be the same as non-infected patients. (1B)
• HIV donors are unsuitable for donation (1D) Suggestion
• Disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality Recommendation
• Follow the same guidelines on the ethics for all donors (Not graded)
• Standard of consent should be the same (Not graded)
• Transplant team must be satisfied that donor consent is adequate (Not graded)
Suggestion
• Encourage the recipient to disclose HIV diagnosis to their donor (Not graded)
• Donors are asked about any condition cause them to change their decision to donate, without highlighting HIV (Not graded)
• Donors should be aware about that medical and social or confidential information about the recipient that is not disclosed (Not graded)
Use of HIV-infected donors for HIV-infected recipients Recommendation
• Using HIV-infected organs is restricted to organs from DD with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Genotype patterns where possible and current viral load
c) No virological failure or drug resistance (1D)
• Recipients are counseled and give informed consent (1D) Suggestion
• LD with HIV-infection are considered for donation (1D)
• The use of HIV+ organ is restricted to experience centers (Not graded)
⭐⭐⭐BTS guidelines; Kidney & Pancreas Transplantation in Patients with HIV
Summary:
· Kidney transplantation in HIV recipients:
o All potential kidney transplant recipients must be screened for HIV infection
o HIV per se is not an absolute contraindication for kidney transplantation, and should have access to living donor transplantation as non HIV casesprovided that: if adherent to treatment, particularly combined anti-retroviral therapy (cART) + CD4+ T cell counts are stable in preceding 3 months at level >100 cells/µL (ideally > 200 cells/ µL) + undetectable HIV RNA in the previous 6 months + No opportunistic infections documented during the previous 6 months+ no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
o Choose appropriate therapy with HIV expert prior to transplantation (take care of drug-drug interaction).
· Absolute Contraindication to transplantation in HIV;
o Uncontrolled HIV infection (CD4+ T cell levels persistently <100).
o Persistent +ve PCR in last 3 months.
o None adherence to therapy (psychiatric problem-drug abuse).
o Multi-drug resistant HIV.
o +ve CDC crossmatch.
o Active infection/malignancy or pregnancy.
· Relative contraindication to transplantation in HIV;
o Positive FCXM, ABOi or increased HLA mismatch (as they need desensitization protocols that flare up HIV).
o Treated malignancy, including extracutaneous Kaposi sarcoma,
o Severe and/or uncontrolled medical problems that will shorten the patient’s life expectancy as Chronic liver disease, Marked obesity (BMI >35), HTLV infection.
· So 3 important parameters in follow up and monitoring of HIV cases (HIV PCR, any viral resistance pattern, CD4 T cell count, treatment used and adherence) should be done prior to transplantation to determine if possible to transplant or not (and 1 month after transplantation, then every 3 months during 1st year, then every 3-6 months thereafter).
· Additional Testing /screening for syphilis, HSV, EBV, CMV, VZV, human T-cell leukaemia virus and Toxoplasma gondii, latent TB (Quantiferron test/IGRA).
· Latent TB should be screened for active TB (smear with Zn stain, CXR, geneXpert, rapid culture on BACTEC system), if positive treatment is essential prior to transplantation. If just latent infection is treated with prophylactic anti TB regimen prior to transplantation. If exposure occurs after transplantation, reevaluation is essential.
· Screen for hepatitis as: HB S Ag or HCV antibody, then PCR quantified and Us screening for liver cirrhosis. (HBV infection must be treated prior to transplantation). If Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but better avoid lymphodepletion therapy.
· screen for Strongyloides stercoralis infection prior to transplantation in transplant candidates from endemic regions.
· Screen for cervical/anal cancer, cases with cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation.
· Nephrotoxic antiretrovirals (specific tenofovir formulations and atazanavir) are better avoided in kidney transplantation, Antiretrovirals with significant drug-drug interactions with CNI (ritonavir and cobicistat) are avoided in the setting of SOT.
· Pancreas transplantation (either isolated as in uncontrolled diabetic state or combined with kidney in diabetic nephropathy).
o Kidney and/or pancreas transplantation is contraindicated in patients with liver cirrhosis, active HCV replication, Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or EBV- related lymphoma.
· Pre-transplant immunization:
o HBV vaccine is administered to all non-immune patients (HBV S antibody titres <10 mIU/mL).
o HAV vaccine is administered to all non-immune patients
o Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients
o Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL
o Annual Influenza vaccine.
o DPT and MMR to all none immune cases.
· Drug-drug interaction between CNI and anti-retroviral therapy;
o Try CNI before transplantation to adjust dose.
o Avoid protease-inhibitors (PI)-based antiretroviral.
o Best in KT is to use DNA integrase inhibitors.
· Immunosuppressive therapy: induction with basiliximab and tacrolimus based triple maintenance IS therapy with steroids +MMF. In addition, treatment of rejection episodes is the same as HIV –ve recipients.
· Chemoprophylaxis against PJP and CMV is the same as none HIV (CMV D+/R-) should receive 3-months prophylaxis, while CMV D+/R+ should have PCR monitoring and preemptive therapy).
· Toxoplasma IgG seropositive recipients with a CD4+ count <200, with positive donor (receive life-long prophylaxis).
· Donation to HIV +ve recipient needs disclosure about the recipient’s morbidity and mortality risk (better by the recipient himself), but not the recipient’s HIV other medical or social status, with standard obtaining of
· HIV + ve recipient is accepted, but consider absolute CI to living donation.
· Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors and to HIV +ve recipientswith:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Information regarding donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance to decrease risk of transmission of viral resistance.
· Recipients are counselled and obtain informed consent both at the time of listing and at the time of transplantation.
· Patients with HIV-infection are unsuitable to be livingkidney donors (1D)
· HIV+ organ use is restricted to centers that have experience in transplanting HIV+ patients (Not graded)
BackgroundAs per a report from 2013, 108,000 people were living with HIV in the UK. The use of combination antiretroviral therapy (cART) has led to a decrease in opportunistic infections and death. Immunodeficiency is an important risk factor for chronic kidney disease (CKD) and end-stage kidney disease (ESRD).
HIV-associated nephropathy (HIVAN) is the most severe form of CKD and one of the commonest cause of ESRD in HIV-positive patients. Patients with HIVAN are typically young (mean age 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median estimated glomerular filtration rate [eGFR] 21 mL/min/1.73m2) at diagnosis.
Suppressing HIV replication may improve or stabilize kidney function, but a majority of patients may still progress to ESRD. Kidney transplantation in HIV-positive patients is complicated due to a high rate of acute allograft rejection. However, immune suppression is noted to be well tolerated, with fewer patients experiencing opportunistic infections.
HIV infection is not associated with an increased risk of diabetes mellitus. However, the use of cART has been associated with metabolic syndrome and diabetes mellitus.
Indications for kidney transplantationRecommendations
It is recommended that all potential kidney transplant recipients are screened for HIV infection and HIV per se is not a contraindication for kidney transplantation.
Wait-listing HIV patients should only occur if:
They are concordant with treatment, particularly cART therapy
Their CD4+ T cell counts are >100 cells/µL (ideally >200 cells/µL) and have been stable during the previous 3 months
HIV RNA has been undetectable during the previous 6 months
No opportunistic infections have occurred during the previous 6 months
They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
It is suggested that the most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication. RationaleIt is noted that select patient groups have shown positive results after transplantation. It is recommended that the following criteria should be met:
Patients demonstrate overall concordance with recommended treatment, and with cART therapy in particular
CD4+ T cell levels are a minimum of 100 cells/µL and ideally >200 cells/µL and have been stable during the last 3 months
HIV RNA has been undetectable during the last 3 months
No opportunistic infections have occurred during the last 6 months
No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
The reported higher rejection rate in some studies can potentially be attributed to the difficulty in obtaining a good balance between immunosuppression and controlled viral replication. It is suggested that the most appropriate anti-retroviral therapy for an individual patient should be discussed with the HIV/infectious disease team before transplantation.
Indications for pancreas transplantationRecommendationsIt is suggested that diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation, and that diabetic patients with severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min).
It is recommended that such patients are assessed by a center with experience in kidney transplantation in HIV-positive patients and in solitary pancreas or islet transplantation. RationaleThere is relatively little experience with simultaneous pancreas–kidney transplantation in HIV-positive patients with diabetes mellitus. Extrapolating the results seen in selected HIV-positive patients receiving kidney transplants, it is recommended that diabetic patients with kidney failure and controlled HIV infection may be considered for simultaneous kidney and pancreas transplantation.
In the general population, if a patient suffers from life-threatening hypoglycemic unawareness despite good diabetic care, islet cell transplantation or solitary pancreas transplantation may be considered. Unfortunately, there is no published experience of this type of transplantation in HIV-positive patients. If transplantation is considered, it is recommended that patients are assessed by a center that regularly performs both solitary pancreas or islet transplantation and also kidney transplantation in HIV-positive patients.
Contraindications to transplantationRecommendationsIt is recommended that the following are absolute contraindications to kidney transplantation in patients with HIV:
Uncontrolled HIV infection (CD4+ T cell levels persistently <200 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months)
Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse
Multi-drug resistant HIV infection that cannot be controlled with currently available ART
Serious ongoing or recurring infection, including documented history of PML
Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer
Pregnancy
It is suggested that the following are relative contraindications to kidney transplantation:
Positive flow cytometric crossmatch (FCXM)
Blood-type incompatibility
Treated malignancy, including extracutaneous Kaposi sarcoma
Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy
Chronic liver disease
Marked obesity (BMI >35 kg/m2)
HTLV infection
General assessmentRecommendation
It is recommended that existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease.
RationaleThere is no evidence that general assessment for transplant candidacy should be different for HIV-infected and non-HIV-infected kidney and pancreas transplant candidates.
HIV-specific assessmentRecommendationsIt is recommended that:
All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile.
Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications.
Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukemia virus and Toxoplasma gondii.
Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines.
Transplant candidates are tested for latent Mycobacterium tuberculosis infection following the testing strategy for immunocompromised HIV infected patients in the current NICE Tuberculosis Guidelines
Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease
Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation
Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation
Transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and undergo investigation for the presence of liver cirrhosis
Hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed
Against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication
Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation
Against solid organ transplantation in patients with a history of extracutaneous Kaposi sarcoma, Castleman’s disease, human herpes virus 8 (HHV8) related primary effusion lymphoma or Epstein-Barr virus (EBV)-related lymphoma
It is suggested that in selected cases:
Solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL.
Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available.
Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available.
Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation.
Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy)
RationaleIt is important to ensure that infectious complications post-transplantation are minimized through screening, immunisation and/or the provision of treatment and to formulate a management plan that allows the safe co-administration of combination antiretroviral therapy (cART) and immunosuppression.
The 2005 BTS guidelines proposed that HIV-positive patients who are considered for kidney transplantation should have CD4 cell counts above 200 cells/µL, undetectable HIV RNA levels, and future antiretroviral options. It is unclear whether patients with CD4 cell counts below 200 cells/µL but with fully suppressed HIV RNA levels are at greater risk of infectious complications post-transplantation. Therefore, it appears that, in carefully selected cases, solid organ transplantation may also be an option for patients with fully suppressed HIV RNA and an absolute CD4 cell count below 200 cells/µL. The appropriate cART regimen for patients awaiting solid organ transplantation is determined by the presence of HIV resistance mutations and the recipient’s ability to tolerate specific antiretrovirals.
It is also important to know whether potential transplant recipients have had exposure to the common herpes viruses: herpes simplex virus (HSV); Epstein-Barr virus (EBV); cytomegalovirus (CMV); and varicella zoster virus (VZV).
Solid organ transplant recipients are at increased risk of developing tuberculosis (TB). TB post-transplantation is a serious complication; the diagnosis of TB is challenging and its treatment complex in patients on antiretroviral and immunosuppressive therapy.
The prevalence of hepatitis B (HBV) and hepatitis C (HCV) is increased in HIV-positive patients. There are high rates of liver disease progression (cirrhosis, hepatocellular carcinoma) that have been reported in untreated HBV co-infected patients who underwent kidney transplantation. Among HIV-positive kidney transplant recipients, a higher early mortality has been observed for those co-infected with HCV.
The incidence of human papilloma virus (HPV)-associated cancer and Kaposi sarcoma (KS) are markedly increased in both HIV-positive patients and kidney transplant recipients.
Pancreas-specific assessmentRecommendationsIt is recommended that pancreas transplantation assessment in patients with HIV includes:
Vascular assessment (ultrasound assessment of leg vessels, and consider non-contrast CT of aorta and iliac arteries)
Consideration of a more extensive cardiac assessment.
It is recommended that assessment of these patients is performed in a center that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation and that the transplant candidate is carefully counselled and informed that there is currently relatively little experience of pancreas transplantation in HIV-infected patients. RationaleThe patients assessed for pancreas transplantation should ideally also be assessed for the presence of hypoglycemic unawareness, peripheral neuropathy, and autonomic neuropathy. A C-peptide level must be measured to determine whether the transplant candidate has type I or type II diabetes. Most patients will require a more extensive vascular assessment to include ultrasound assessment of leg vessels, and possibly non-contrast CT assessment of the aorta and iliac arteries.
Pre-transplant immunizationRecommendationsAs part of the work-up for solid organ transplantation it is recommended that:
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL)
Hepatitis A virus (HAV) vaccine is administered to all non-immune patients
Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients
Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL.
It is suggested that:
Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients
Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles
Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition
It is also recommended that influenza vaccine is administered annually to patients awaiting solid organ transplantation. RationaleHBV vaccination significantly reduces the risk of incident HBV infection in HIV positive persons. It is recommended to immunize those with a high risk of hepatitis A infection. It is safe and well tolerated in HIV-infected patients and those with end-stage kidney disease.
Pneumococcal vaccination is recommended for all HIV positive patients with CD4 cell counts >200 cells/µL, and for those with CD4 cell counts <200 cells/µL if there are additional risk factors such as chronic kidney and liver disease or diabetes mellitus. Vaccination should be repeated every 3-5 years.
HIV-positive persons and solid organ transplant recipients have a higher frequency of zoster than the general population. Guidelines recommend VZV vaccination for asymptomatic, VZV IgG seronegative HIV positive adults with a CD4 cell count >400 cells/µL and suggest that vaccination may also be considered for patients with CD4 counts of 200-400 cells/µL who are stable on cART.
Diphtheria, tetanus and pertussis vaccine is safe and it is a recommended vaccination for all HIV-positive persons in accordance with standard recommendations. And for patients who have been previously vaccinated, a booster dose should be administered.
Guidelines recommend that HIV-positive persons be screened for measles IgG and offered MMR vaccine if they are measles IgG seronegative and asymptomatic with a CD4 count >200 cells/µL. Influenza vaccination is recommended for all HIV-positive patients.
Consideration of drug-drug interactionsRecommendations
A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point and a dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant.
It is also suggested that pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions.
It is recommended continuation of antiretroviral therapy in the perioperative period following transplantation.
It is suggested that all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource. Rationale The general objectives for the preparation for solid-organ transplantation are to ensure that all medicines are reviewed prior to transplantation for potential drugdrug interactions and that the recipient receives optimal doses of calcineurin inhibitors (CNI) to reduce the risk of graft rejection. The first step in preventing harm, and in recognising medication error when it occurs, is to ensure current and complete medication recording. To optimise CNI concentrations following transplantation and help manage the drug-drug interactions between immunosuppressant drugs and ART, a dose-finding trial of CNI immunosuppression with therapeutic drug monitoring may be considered as part of the workup for solid organ transplantation, and is recommended in patients whose cART contains protease-inhibitors. It is critical that both clinicians and patients are aware of the implications of the drug interactions between cART and immunosuppressants, and that the timing of doses and immunosuppressant concentrations, as well as drug dosages and frequencies, are properly communicated and documented.
Induction and maintenance immunosuppressionIt is recommended:
All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation.
For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA)
HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent.
It is suggested that:
Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients.
Rationale The evidence base for the use of lymphocyte-depleting agents in HIV-positive kidney transplantation is very limited. In non-HIV kidney transplant recipients, there is good evidence to support the use of tacrolimus for maintenance therapy, over ciclosporin in terms of reduced acute rejection and graft survival. There is some evidence to suggest that ciclosporin, and in particular mTOR inhibitors may have an anti-HIV effect including, in the case of mTORs, decreased CCR5 expression and viral reactivation. There is insufficient data in HIV-positive patients to make absolute recommendations on the best maintenance immunosuppressive regimen.
Post-transplant prophylaxisRecommendationsIt is recommended that:
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation.
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months.
CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months.
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation.
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing.
It is suggested that:
Toxoplasma IgG seropositive recipients with a CD4 + count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis.
Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4 + count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months
RationaleIn general, anti-Pneumocystis prophylaxis is recommended for all non-HIV-infected solid organ transplant recipients for at least 3-6 months post-transplant. Toxoplasmosis in transplant recipients can occur through ingestion of contaminated food or water, after receiving an infected allograft, or by reactivation of latent infection.
To avoid primary infection, transplant recipients should avoid contact with undercooked meat, soil, water or animal faeces that might contain toxoplasmosis cysts.
The routine use of co-trimoxazole for post-transplant PCP prophylaxis has decreased the risk of toxoplasmosis and is the most effective prophylaxis against this parasite.
In HIV-positive patients, co-trimoxazole 960 mg once daily is recommended as first line prophylaxis.
The two major strategies for cytomegalovirus (CMV) prevention are antiviral prophylaxis and pre-emptive therapy. Valganciclovir is the preferred prophylactic agent, and in general should be started as early as possible and within the first 10 days after transplantation.
Monitoring allograft functionRecommendationsIt is recommended that existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease.
It is suggested that local practice for monitoring of the pancreas allograft is followed. RationaleThere is no evidence that post-operative care should be different for HIV-infected and noninfected kidney and pancreas transplant candidates.
Monitoring of HIV virological controlRecommendations
It is recommended that quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months thereafter.
It is also recommended that if patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options.
It is suggested that more frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis. RationaleAnti-viral treatment that is insufficient to completely suppress viral replication imposes a selective pressure that may result in the emergence of drug-resistant viral escape mutants. HIV drug resistance testing is thus part of the standard management of patients in whom viral replication is not suppressed.
Choice of living versus deceased kidney donor RecommendationsIt is recommended that patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients and that patients with HIV infection are unsuitable to be living kidney donors.
It is suggested that potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory.
RationaleLiving kidney donation yields superior outcomes relative to deceased donor transplantation. A recent survey found that HIV-infected patients have less knowledge about living donor kidney transplantation, have more concerns about living donor kidney transplantation, and are less willing to pursue living donor kidney transplantation than those without HIV.
Most perceive their HIV status to be a barrier to living donor kidney transplantation. Given the increased risk of kidney disease in HIV-infected patients the use of such patients as living kidney donors, even with well-controlled HIV, is not recommended.
Consent and confidentialityRecommendationsIt is recommended that:
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance
It is suggested that:
Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor
All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV
All living donors are made aware that there may be medical and social information about the recipient that is not disclosed
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant
RationaleIt is recommended that all health professionals involved in transplantation should acknowledge the wide range of complex moral issues that are associated with this area of clinical practice and ensure that good ethical practice consistently underpins clinical practice to achieve optimum outcomes.
Use of HIV-infected donors for HIV-infected recipients Recommendations:It is recommended that transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
Information about the donor virus such as historical genotype patterns where possible and current viral load
No history of virological failure or drug resistance.
It is also recommended that recipients are counselled and give informed consent both at the time of listing and at the time of transplantation and that patients with HIV-infection are unsuitable to be living kidney donors.
It is suggested that HIV+ organ use is restricted to those centers that have experience in transplanting HIV+ patients.
RationaleThere is a risk of transmission of opportunistic infection from the donor. HIV infection can cause organ damage such as chronic kidney disease due to HIV-associated nephropathies, and the recipient should be counselled about this risk. Preimplantation biopsies may be considered to detect donor disease. Given the increased risk of kidney disease in HIV-infected patients, the use of such patients as living kidney donors, even with well-controlled HIV, is not recommended.
Kidney & Pancreas Transplantation in HIV Patients
HIV patients who might be listed for kidney transplantation have the following criteria:
– With cART, CD4 count > 100 (preferably > 200), stable > 3 M, no opportunistic infection in the last 6 M, and undetectable HCV RNA
No prior history of lymphoma, chronic intestinal cryptosporidiosis, or progressive multifocal leukoencephalopathy is required.
When HIV is stable, these are the reasons for a pancreas transplant:
SPK with controlled HIV
Pancreas with severe low blood sugar and an eGFR of more than 40mL/min
Absolute contraindication to transplantation of HIV patients
Uncontrolled HIV infection, a low CD4 count that doesn’t go up, and a viral load that can be seen.
Uncontrolled HIV infection that is resistant to multiple drugs
Positive complement-dependent cytotoxic (CDC) crossmatch
Serious or recurrent infections, cancer, or being pregnant
Relative contraindication to transplantation of HIV patients:
a) Positive flow cytometric crossmatch
b) ABO incompatibility
c) Treated malignancy, including extracutaneous Kaposi sarcoma
d) Severe and/or uncontrolled medical problems that are unlikely to improve after
kidney transplantation and will shorten the patient’s life expectancy
e) Chronic liver disease
f) Marked obesity (BMI >35 kg/m)
g) HTLV infection Pretransplant assessment
– HLA-B5701 status, CD4 cell count, HIV RNA level, current and previous antiretroviral therapy, HIV resistance profile, and HIV resistance profile – Syphilis, HSV, HZV, EBV, CMV, varicella zoster virus, HTCL virus, and Toxoplasma gondii
– TB screening: use an interferon test to check for latent infection -gamma test with or without a concomitant Mantoux test; in the event of a positive result, seek for active infection and treat both active and latent infection as in the general population.
– Screening and treatment for viral hepatitis
– check for occult malignancies in particular genito-urinary neoplasia
– In endemic locations, check for Strongyloides stercoralis
Immunization prior to transplant
HBV surface antibody titres lower than 10miu/ml in non-immune individuals should necessitate HEP B vaccine.
All eligible patients will receive the Hep A and pneumococcal vaccines.
VZV will be administered to non-immune patients with CD4 counts above 200 cells per ul, and those awaiting SOT will receive the influenza vaccination yearly.
All eligible patients receive DPT.
MMR is given to those who have never had the measles, whereas HPV is given to people who are at risk of getting the virus. Drug–drug interaction suggestion
A complete and current medication review as part of solid organ transplantation assessment, done at least twice a year and at crucial treatment decision points
A calcineurin-inhibitor dose-finding trial before solid organ transplantation to estimate post-transplant dosages.
If possible, avoid enhanced protease-inhibitors (PI)-based antiretroviral regimens to reduce medication interactions.
All clinical correspondence includes a footer pointing practitioners to the Liverpool HIV Drug Interactions Portal. Induction and maintenance immunosuppression
All HIV-positive kidney transplant candidates get induction treatment.
Most HIV-positive individuals receive interleukin-2 receptor antagonist induction treatment.
HIV-positive kidney transplant recipients receive steroids, a calcineurin inhibitor, and an anti-proliferative drug for maintenance immunosuppression.
HIV-positive kidney transplant recipients are treated the same for acute rejection.
Post-transplant prophylaxis
HIV-positive transplant recipients receive lifetime Pneumocystis pneumonia prevention.
CMV seronegative recipients of organs from CMV-positive donors should receive cytomegalovirus prophylaxis for at least three months.
CMV seropositive transplant recipients get either prophylaxis or PCR surveillance and pre-emptive medication for 3 months.
Healthy transplant patients who were not screened and treated for Mycobacterium TB latent infection or illness before transplantation should be assessed as recommended.
Transplant patients who are well and were assessed and treated for Mycobacterium TB latent infection or illness before transplantation do not need reassessment unless they have been exposed to tuberculosis.
According to NICE TB contact tracing recommendations, transplant patients who are re-exposed to tuberculosis should be tested for latent infection and illness.
Toxoplasma IgG seropositive receivers with a CD4+ count <200 cells/μL or organ recipients from seropositive donors receive lifelong prophylaxis.
If there is a solid history of treated TB infection, symptom evaluation and chest X-ray are sufficient diagnostics, and TB prophylaxis is not needed until re-exposure is suspected.
Prophylaxis against MAC is recommended when the CD4+ level is fewer than 50 cells/μL and ceased after 6 months when it is greater than 100.
Allograft monitoring
All HIV-positive kidney transplant recipients follow post-operative instructions.
Pancreas allograft monitoring based on local practice and protocols.
HIV virus surveillance
Quantitative HIV RNA and CD4+ T-cell counts are measured at 1 month after transplant, then every 2-3 months for the first year, then every 3-6 months after that.
Drug-resistance testing determines treatment options for HIV viremia.
Depleting antibodies may require more frequent CD4 count monitoring to evaluate anti-infective treatment. HIV-positive donors and recipients
HIV viral load <50 copies/mL and CD4 count >200/μL for at least six months prior to brain damage.
Genotype patterns and viral load of the donor virus.
No pharmacological or viral failure.
Both donor and recipient are counseled and give informed consent.
HIV-positive people cannot donate kidneys.
Only HIV+ transplant centers can use HIV+ organs.
• The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
HIV-specific assessment
• All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
• Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
• Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
• Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing
strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
• Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
• Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
• Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
• All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis(1C)
• All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
• Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
Pre-transplant immunisation
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
• Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
• Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
• Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/μL (1C)
• Influenza vaccine is administered annually to patients awaiting solid organ
transplantation (1B)
Consideration of drug-drug interactions
• Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
Induction and maintenance immunosuppression
• All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
• For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
Post-transplant prophylaxis
• HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
• Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
• CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
Monitoring allograft function
• Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
Monitoring of HIV virological control
• Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
• If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
Choice of living versus deceased donor
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D
Consent and confidentiality
• Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
• The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
• Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded)
Use of HIV-infected donors for HIV-infected recipients
• Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Information about the donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
• Patients with HIV-infection are unsuitable to be living kidney donors (1D)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Kidney & Pancreas Transplantation in Patients with HIV
1. Indications for Kidney transplantation We recommend that: a) All potential kidney transplant recipients are screened for HIV infection (1D) b) HIV per se is not a contraindication for kidney transplantation (1B) c) HIV-positive patients are wait-listed only if: I. They are concordant with treatment, particularly cART therapy (1D) II. Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months (1B) III. HIV RNA has been undetectable during the previous 6 months (1B) IV. No opportunistic infections have occurred during the previous 6 months (1B) V. They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B) We suggest that: · The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded) 2. Indications for Pancreas Transplantation We recommend that: · Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded) We suggest that: a) Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded).
3. Contraindications to transplantation
We recommend that: The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
We suggest that: The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
4. General assessment
We recommend that:
· Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded)
5. HIV-specific assessment
We recommend that: a) All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D) b) Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C) c) Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D) d) Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C) e) Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C) f) Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C) g) Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C) h) All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C) i) All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B) j) Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
We recommend against:
a) Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C) b) Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1D) We suggest that: a) In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/μL but above 100 cells/μL (2C) b) Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded) c) Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D) d) Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D) e) Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
6. Pancreas-specific assessment We recommend that: a) Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C) b) Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded) We suggest that:
Pancreas transplantation assessment in patients with HIV includes: a) Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy) b) Vascular assessment (ultrasound assessment of leg vessels, and consider non- contrast CT of aorta and iliac arteries)
c) Consideration of a more extensive cardiac assessment (2C)
7. Pre-transplant immunisation We recommend that: a) Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B) b) Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D) c) Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B) d) Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/μL (1C) e) Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B) We suggest that: a) Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D) b) Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D) c) Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition(2C) 8. Consideration of drug-drug interactions We recommend:
· Continuation of antiretroviral therapy in the perioperative period following transplantation (1D) We suggest:
a) A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
b) A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
c) Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
d) That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
9. Induction and maintenance immunosuppression We recommend that:
a) All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
b) For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
c) HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C) We suggest that:
· Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D) 10.Post-transplant prophylaxis We recommend that:
a) HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
b) Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
c) CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
d) Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
e) Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need re- assessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
f) Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C) We suggest that:
a) Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/μL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
b) Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
c) Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/μL, and it be stopped when the CD4 count is >100 cells/μL for 6 months (2D) 11.Monitoring allograft function We recommend that:
· Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded) We suggest that:
· Local practice for monitoring of the pancreas allograft is followed (Not graded) 12.Monitoring of HIV virological control We recommend that:
· Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
· If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D) We suggest that:
· More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D) 13.Choice of living versus deceased donor We recommend that:
a) Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
b) Patients with HIV infection are unsuitable to be living kidney donors (1D) We suggest that:
· Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded) 14.Consent and confidentiality We recommend that:
a) Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
b) The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
c) Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded) We suggest that:
a) Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
b) All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
c) All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
d) All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
15.Use of HIV-infected donors for HIV-infected recipients We recommend that:
a) Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with: Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
I. HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
II. Information about the donor virus such as historical genotype patterns where possible and current viral load
III. No history of virological failure or drug resistance (1D)
b) Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
c) Patients with HIV-infection are unsuitable to be living kidney donors (1D) We suggest that:
· HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded).
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Kidney & Pancreas Transplantation in Patients with HIV, BTS, second edition 2015
Indications for Kidney transplantation
HIV is not a contraindication for kidney transplantation. HIV-positive patients are wait-listed only if:
Adherent with treatment is essential.
CD4+ T cell counts should be >100 cells/µL (ideally >200) and stable during the previous 3 months.
Negative HIV RNA level for the last 6 months.
No opportunistic infections in the last 6 months.
No history of progressive multifocal leukoencephalopathy or lymphoma.
Indications for Pancreas Transplantation
Diabetic HIV patients with controlled HIV infection and in renal failure are candidates for simultaneous kidney and pancreas transplantation.
Solitary pancreas or islet transplantation can be carried out if they have well controlled HIV and their kidney function is stable at eGFR >40mL/min.
Absolute Contraindications to transplantation
Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months.
Non-compliance due to major psychiatric disease/ persistent substance abuse.
Multi-drug resistant HIV infection.
Serious ongoing or recurring infection.
Active malignancy.
Positive CDC crossmatch.
Pregnancy
Relative contraindications to kidney transplantation
· Positive FCXM
· Blood group incompatibility
· Recently Treated malignancy
· Severe chronic liver disease, Marked obesity, and HTLV infection
HIV-specific assessment
CD4 cell count and HIV RNA levels should be carefully assessed and monitored.
Tested for active or latent infections of syphilis, HSV, EBV, CMV VZV, HTL virus and Toxoplasma gondii.
Also, test should be done for latent TBI with an IGRA test. Transplant candidates with latent TBI, should be treated prior to transplantation.
All transplant candidates are screened for viral hepatitis. If found to be HBs Ag positive or HCV antibody positive should be assed and treated according to current guideline.
Pre-transplant vaccination include:
· HBV and HAV vaccine, Pneumococcal polysaccharide vaccine, Influenzas vaccine, VZV vaccine is administered to patients with CD4 cell counts >200 cells/µL
Induction and maintenance immunosuppression
All HIV-positive transplant candidate should be offered induction therapy at the time of transplantation with IL-2 antibodies.
HIV-positive patients should be given triple therapy maintenance immunosuppression.
Acute Rejection can be treated in the same way as HIV-negative kidney transplant recipients.
Post-transplant prophylaxis
Lifelong pneumocystis pneumonia prophylaxis.
CMV prophylaxis is indicated in CMV negative recipients if donor is CMV positive.
If CMV seropositive transplant recipients should receive either prophylaxis, or PCR observation and pre-emptive therapy for CMV.
Transplant patients who are re-exposed to TB after transplantation should be assessed for latent infection and/or disease.
Prophylaxis against MAC may be given, when the CD4+ count is ≤ 50 cells/µL, and stopped when the CD4 count is >100 cells/µL for 6 months.
Monitoring kidney function post transplantation
· Should follow the existing guidelines Monitoring of HIV virology
Quantitative HIV RNA and CD4+ T-cell counts should be measured at 1 month after transplant and every 2-3 months for the first year then every 3-6 months later on.
If persistent HIV viraemia, then drug-resistance testing should be performed. Choice of living versus deceased donor
Patients with HIV infection are candidates for living donor kidney transplantation as non-infected patients but are considered unsuitable.
Consent and confidentiality
In HIV-positive transplant candidates you should follow the standard of consent as for any other transplant candidate.
All living donors should be aware that there may be confidential information about the recipient which are not disclosed. (Because they are not relevant to the transplant outcome).
If possible, the recipient is asked to disclose their diagnosis of HIV to their donors.
Use of HIV-infected donors for HIV-infected recipients
· Patients with HIV-infection are unsuitable for living kidney donation.
· Deceased donors should have HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury.
· If possible, Information such as genotype and current viral load should be obtained.
· Should have no history of virological failure or drug resistance.
Kidney & Pancreas Transplantation in Patients with HIV British Transplantation Society Guidelines 2015. Indications for Kidney transplantation They recommend that:
All potential kidney transplant recipients are screened for HIV infection (1D)
As HIV itself not a contraindication for kidney transplantation (1B)
There are specific criteria for HIV-positive patients listed on waiting list such as :
a) patients who are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma (1B) Indications for Pancreas Transplantation They suggest that:
• Simultaneous kidney and pancreas transplantation for diabetic patients in renal failure and with controlled HIV infection (2D)
• Diabetic patients with severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded) Contraindications to transplantation They recommend that: • Absolute contraindications to kidney transplantation in patients with HIV are :
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, including documented history of PML & active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
f) Pregnancy (1D) They suggest that:
• The following are relative contraindications to kidney transplantation:
a) Positive flow cytometry crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extra cutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after
kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease and marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D) General assessment HIV-specific assessment: They recommend that:
• All transplant candidates should reviewed by CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
• Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
• Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Monteux test(1C)
• Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation and also latent TB (1C)
• Screening for HBV and HCV and treatment for positive cases (1C)
• Screening for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D) We recommend against:
• Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication and a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1C) We suggest that:
• In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/μL but above 100 cells/μL(2C).
• Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
• Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, unless lympho-depletion therapy given) (2D) Pancreas-specific assessment They suggest that:
• Pancreas transplantation assessment in patients with HIV includes:
a) Diabetic assessment (for hypoglycemic unawareness, peripheral neuropathy, &
autonomic neuropathy)
b) Vascular assessment (ultrasound assessment of leg vessels, and consider non-contrast CT of aorta and iliac arteries)
c) Consideration of a more extensive cardiac assessment (2C) Pre-transplant immunization They recommend vaccination:
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titers <10 mIU/mL) (1B)
• Hepatitis A virus (HAV) vaccine, Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
• Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/μL (1C)
• Influenza vaccine is administered annually to patients awaiting solid organ
transplantation (1B) They suggest that:
• Diphtheria, tetanus and pertussis (DTP), (MMR) vaccine is administered to all patients (2D) Consideration of drug-drug interactions They recommend:
• Continuation of antiretroviral therapy in the perioperative period following transplantation (1D) We suggest:
• A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
• Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimize drug interactions (2D) Induction and maintenance immunosuppression We recommend that:
• All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
• Induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C) We suggest that:
• Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D) Post-transplant prophylaxis We recommend that:
• HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
• Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A) They suggest that:
• Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/μL or any
recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong
prophylaxis (2C)
• Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/μL, and it be stopped when the CD4 count is >100 cells/μL for 6 months (2D) Monitoring allograft function We recommend that:
• Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B) We suggest that:
• More frequent monitoring of CD4 count may be necessary in patients receiving
depleting antibodies to determine the need for anti-infective prophylaxis (2D) Choice of living versus deceased donor We recommend that:
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D) We suggest that:
• Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality We recommend that:
• The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
• Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded) We suggest that:
• Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
• All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
• All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded) Use of HIV-infected donors for HIV-infected recipients We recommend that:
• Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Information about the donor virus such as historical genotype patterns where
possible and current viral load
c) No history of virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
• Patients with HIV-infection are unsuitable to be living kidney donors (1D).
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney & Pancreas Transplantation in Patients with HIV (JAn 2017) Indications for Kidney transplantation HIV patients can be listed for Tx if they are stable as follow:
On cART, CD4 count > 100 (ideally >200) and stable > 3 M
Last 6M no opportunistic infection and HCV RNA undetectable
no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
Indications for Pancreas Transplantation with stable HIV:
SPK with stable HIV
Pancreas with severe hypoglycaemic unawareness and eGFR >40mL/min
Contraindication absolute Uncontrolled HIV infection, persistent low CD4 count and detectable viral load. Multi-drug resistant uncontrolled HIV infection Positive complement-dependent cytotoxic (CDC) crossmatch Serious ongoing or recurring infection, cancer or pregnant
TB: test for latent infection with an interferon-gamma test with or without a concurrent Mantoux test, if positive look for active infection and treat both active and latent infection as in general population
Viral hepatitis screen and treat, Anti-HBc positive “alone” recipients with ATG gets prophylaxis
Cervical and anal neoplasia
Screen for r Strongyloides stercoralis in endemic areas
A) ARV Avoid ARV with nephrotoxic potential ( tenofovir and atazanavir) Avoid those with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org)
B) dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
C) Induction and maintenance immunosuppression Induction with interleukin-2 receptor antagonist (IL-2RA) Maintenance with steroid + CNI + antiproliferative Rejection as non HIV patients
Post-transplant prophylaxis PCP – life long CMV – as non HIV MAC: CD count < 50 and stop if > 100 Toxoplasma: IgG+ve recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor positive receive lifelong prophylaxis
Monitor HIV RNA and CD4 count post transplant
Choice of living versus deceased donor HIV +ve not suitable for live donation
Use of HIV-infected donors for HIV-infected recipients when donor CD4 count > 200 and viral load < 50 in the past 6M with no hx of virological resistance or failure
In 2013 108,000 people were living with HIV in the UK. The use of combination antiretroviral therapy (cART) has led to a dramatic reduction in opportunistic infections and death, and to be provided to patients with CD4 cell counts of less than 350 cells/µL, with 87% of those on cART achieved viral suppression. Immunodeficiency is an important risk factor for chronic kidney disease (CKD) and end-stage kidney disease (ESRD) (6,7), and for liver disease progression in HCV-co-infected patients (8). HIVAN is the most common cause of end stage renal disease in HIV patients, usually black, young /,36 years with a low CD4 < 66 copies/ml. Kidney transplantation in the era of c-ART is associated with good overall outcome in HIV patients in the term of graft survival and infectious complications, but some increased risk of rejection reaching 36%. Indications of kidney transplant of HIV patients:
· All potential kidney transplant recipients are screened for HIV infection (1D). · HIV per se is not a contraindication for kidney transplantation (1B). · HIV-positive patients are wait-listed only if: a) They are concordant with treatment, particularly cART therapy (1D). b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B). c) HIV RNA has been undetectable during the previous 6 months (1B) d) No opportunistic infections have occurred during the previous 6 months (1B). e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B). · The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded).
Indications for pancreas transplantation:
· Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded). · Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D) • Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded).
Contraindications to transplantation:
The absolute contraindications to kidney transplantation in patients with HIV are: a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C). b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D). c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D). d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D). e) Serious ongoing or recurring infection, including documented history of PML (1D). f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D). g) Pregnancy (1D) Progressive multifocal leukoencephalopathy (PML), is a rare and fatal viral disease caused by a polyomavirus and occurs almost exclusively in people with severe immune deficiency, with no cure. Recommendations and advice may be obtained from the Israel Penn International Transplant Tumor Registry: · Consultation with an oncologist is required in most cases. In general, a two to five year waiting period is recommended after curative therapy for malignancy, and depends on the followings – (1) the estimated risk of recurrence,(2) extent of disease at the time of treatment,(3) type and grade of tumour, and(4) the treatment given. · Cardiovascular evaluation is mandatory. · Patients with advanced cardiopulmonary disease should be excluded. · Candidates with chronic hepatitis B or C or persistently abnormal liver function testing must have a hepatology evaluation prior to transplantation. Hepatitis B or C infection may be a contraindication to kidney transplantation, especially if there is evidence of active hepatitis or cirrhosis. · Patients with quiescent disease and a benign liver biopsy can proceed to kidney transplantation, although treatment may be required in some. · Recipients with a body mass index over 35 kg/m2 are at increased risk of complications after kidney transplantation, including surgical complications, longer length of stay, increased mortality, and higher risk of post transplant diabetes mellitus. · The human T-cell leukaemia virus (HTLV) is a risk factor for the development of leukaemia and myelopathy after transplantation, persons with HTLV must be informed of this 35 risk before surgery. · A remote history of treated tuberculosis does not contraindicate transplantation. In cases where the history suggests that there may be a persistent subclinical tuberculosis infection, a consultation with an infectious disease expert may assist in the decision to treat the recipient for tuberculosis, and whether it can be done before or after the transplant.
The relative contraindications to kidney transplantation in HIV patients are: a) Positive flow cytometric crossmatch (FCXM) (1D). b) Blood-type incompatibility (2D). c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C). d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D). e) Chronic liver disease (2D). f) Marked obesity (BMI >35 kg/m2 ) (2D). g) HTLV infection (1D).
Assessment of HIV patients pre-transplant:
· All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D). · Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C). · Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D). · Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C). · Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C). · Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C). · Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C). · All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C). · All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B). · Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to . transplantation (1D). Solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C). · Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded). · Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D). · Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D). · Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D). Against transplantation:
· Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C). · Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1D)
Pancreas-specific assessment:
Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C). Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded).
Pancreas transplantation assessment in patients with HIV includes: a) Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy). b) Vascular assessment (ultrasound assessment of leg vessels, and consider noncontrast CT of aorta and iliac arteries). c) Consideration of a more extensive cardiac assessment (2C).
Pre-transplant immunisation:
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres 200 cells/µL (1C). Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B). Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D) • Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D). Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV (2C).
Consideration of drug-drug interactions:
Continuation of antiretroviral therapy in the perioperative period following transplantation (1D). A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded). A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D). Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D). The clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded). Induction and maintenance immunosuppression recommendations:
· All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C). · For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B). · HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C). · Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D). Post-transplant prophylaxis recommendations:
· HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D). · Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A). · CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A). · Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C). · Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C). · Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C). · Toxoplasma IgG seropositive recipients with a CD4+ count 100 cells/µL for 6 months (2D)
Monitoring allograft function:
· Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded). · Local practice for monitoring of the pancreas allograft is followed (Not graded) Monitoring of HIV virological control · Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B). · If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D). · More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D).
Choice of living versus deceased donor:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B).
Patients with HIV infection are unsuitable to be living kidney donors (1D)
Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded).
Consent and confidentiality:
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded).
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded).
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded).
The recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded).
All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded).
All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded).
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
Use of HIV-infected donors for HIV-infected recipients:
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load 200/µL for at least 6 months prior to brain injury.
b) Information about the donor virus such as historical genotype patterns where possible and current viral load.
c) No history of virological failure or drug resistance (1D).
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D).
Patients with HIV-infection are unsuitable to be living kidney donors (1D).
HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
All potential kidney transplant recipients are screened for HIV infection (1D)
HIV per se is not a contraindication for kidney transplantation (1B)
HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
We suggest that:
The most appropriate anti-retroviral therapy should be determined before transplantation to anticipate potential drug interactions and dosing.
—————————————————————————————————————–
Indications for Pancreas Transplantation
We recommend that:
Potential HIV positive pancreas transplant recipients should be assessed by a centre with experience in kidney transplantation and solitary pancreas or islet transplantation.
We suggest that:
Diabetic patients in renal failure and with controlled HIV infection may be considered for simultaneous kidney and pancreas transplantation.
——————————————————————————————————————
Contraindications to transplantation
We recommend that:
The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D) d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D) g) Pregnancy (1D)
We suggest that:
The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m 2 ) (2D)
g) HTLV infection (1D)
—————————————————————————————————————— General assessment
We recommend that:
Existing guidelines should be followed for all potential transplant recipients with HIV.
HIV-specific assessment
We recommend that:
We recommend that all transplant candidates undergo careful immuno-virological and antiretroviral status review, serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii, and testing for latent Mycobacterium tuberculosis infection.
All transplant candidates are screened for viral hepatitis, and those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA /hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis.
Patients considered for solid organ transplantation are assessed for cervical and/or anal neoplasia, advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ.
We recommend against:
Kidney and pancreas transplantation in patients with liver cirrhosis, HCV replication, Castleman’s disease, HHV8-related primary effusion lymphoma, or EBV-related lymphoma.
We suggest that:
Solid organ transplantation may be appropriate for patients with suppressed HIV RNA, CD4 cell count below 200 cells/μL, nephrotoxic potential, significant drug-drug interactions with calcineurin inhibitors, and Strongyloides stercoralis infection.
Anti-HBc positive “alone” recipients do not require routine antiviral prophylaxis.
——————————————————————————————————————-
Pancreas-specific assessment
We recommend that:
Pancreas-specific assessment should be performed in a centre that regularly performs renal and pancreas transplantation in HIV-infected patients.
We suggest that:
Pancreas transplantation assessment in HIV includes diabetic, vascular, and cardiac assessments.
Pre-transplant immunisation should include Hepatitis B, HAV, PPV-23, VZV, and Influenza vaccines.
We suggest that:
Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients, Measles, mumps and rubella (MMR) vaccine to non-immune patients, and HPV vaccine to those at risk.
——————————————————————————————————————- Consideration of drug-drug interactions
Continuation of antiretroviral therapy, medication review, dose-finding trial of calcineurin-inhibitors, pre-emptive switching away from PI regimens, and referral to Liverpool HIV Drug Interactions Resource.
—————————————————————————————————————— Induction and maintenance immunosuppression
Induction and maintenance immunosuppression are recommended for HIV-positive kidney transplantation.
Acute rejection is treated the same way as HIV-negative kidney transplant recipients.
Post-transplant prophylaxis is recommended for HIV-positive transplant recipients, CMV seronegative recipients, and toxoplasma IgG seropositive recipients.
It should be assessed for Mycobacterium tuberculosis latent infection or disease before transplantation, and re-assessed for re-exposure after transplantation.
It should also be stopped when the CD4 count is >100 cells/μL for 6 months.
Monitoring allograft function
Monitoring allograft function and HIV virological control is recommended, with quantitative HIV RNA and CD4+ T-cell counts measured regularly and drug-resistance testing carried out to determine treatment options.
——————————————————————————————————————- Choice of living versus deceased donor
Patients with HIV infection should have the same access to living donor kidney transplantation as non-infected patients, and potential donors should be informed of medical, surgical, and psychological factors.
Consent and confidentiality
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant, and the recipient is encouraged to disclose their diagnosis of HIV to their donor.
All living donors are made aware that there may be medical and social information about the recipient that is not disclosed, and are asked to acknowledge that they will not be given confidential information.
——————————————————————————————————————-
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Recommendations:
HIV+ organ use should be restricted to deceased donors with HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury, and recipients should be counselled and given informed consent.
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that medical and social information about the recipient is not disclosed,
KIDNEY AND PANCREAS TRANSPLANTATION IN PTS WITH HIV – BTS GUIDELINES.
Indications for kidney transplantation.
All potential KTR to be screened for HIV with the knowledge that it is not a contraindication to transplantation.
HIV pts to be wait listed if;
On HAART therapy.
CD4 > 100 and stable for 3/12.
Undetectable HIV RNA in past 6/12.
No OI in 6/12.
No hx of PML, Cryptosporidiosis or lymphoma.
HIV specialist to be looped into mgt pre transplant for best HAART regimen, dosing and DI consideration.
Indications for pancreas transplantation.
Pt to be evaluated in a center experienced in kidney and pancreas transplantation.
DM with ESRD and controlled HIV to have both kidney and pancreas transplantation at the same time.
DM with stable eGFR> 40 but with hypoglycemia episode to get lone pancreas transplant or islet transplantation.
Contraindication to transplantation.
Absolute CI to kidney transplantation;
Uncontrolled HIV ,CD4 <100 in last 6/12,HIV RNA detected in last 3/12.
MDR HIV not controlled on HAART.
+VE CDC.
Recurrent /ongoing infection and a hx of PML.
Active malignancy, mets or untreated ca.
pregnancy.
Relative CI to kidney transplantation.
Positive FCXM.
Incompatible blood group.
Tx malignancy.
Medical problems that will improve with transplant.
CLD.
Obesity >35kg/m2.
HTLV infection.
HIV Specific assessment.
Prior to transplantation do ;CD4,HIV RNA,ART,HLAB5701 status and HIV resistance profile.
Adherent pts with HIV RNA <200 copies to be transplanted.
Prior to transplant, syphilis, herpes simplex, EBV, CMV, VZV, toxoplama gondii and HTLV to be tested.
LTBI to be assessed with IGRA/Mantoux test and any evidence should prompt more testing to R/O an active TB infection which should be treated with current guidelines.
On viral Hep screening, HBaAg +VE or HEP C ab +VE should have the respective RNA done and adequate screening for cirrhosis done.
HBsAg +VE on wait list to be treated until viral load undetectable.
No kidney or pancreas transplant in pts with cirrhosis or active HCV.
No SOT in those with hx of castlemans dx,HH8 primary effusion or EBV lymphoma.
SOT to be considered in those with HIV RNA suppression and CD4 100-200.
Avoid nephrotoxic HAART and regimens with significant DI.
Strongyloides stercolis screened pre transplant in those from endemic areas.
Lone anti HBc+VE recipients to get prophylaxis only if receiving lymphodepleting therapy that increases risk of reactivation.
Pancreas specific tx.
Pt to be assessed in a center with experience in transplanting renal and pancreas pts with HIV,
Pt to be counselled on limitation on experience in HIV and pancreas transplant.
DM, Vascular +/- extensive cardiac evaluation to be done pre transplant.
Pre transplant immunization
All non immune with HBV surface antibody titres <10miu/ml to get HEP B vaccine.
Hep A and Pneumoccal vaccine to be given to all pts eligible.
VZV to be given to non immune pts with CD4 >200 cells/ul,Influenza vaccine to be given yearly to those waiting for SOT.DPT is given to all elligible patients.
MMR given to those without immunity to measles while HPV is given to those at risk of HPV infection.
Consideration of DDI.
Ct HAART perioperatively.
Twice yearly medical review.
Optimize CNI in SOT to maintain adequate dose to avert graft dysfunction.
Avoid HAART regimen with PI boosted MEDS to decrease DI.
Induction and maintenance immunosuppression.
All HIV pts to be induced pre transplant with an IL2RA.
Triple therapy to be given to HIV KTR- steroids + CNI +antiproliferative agent.
Approach to acute rejection similar to non HIV population
Post transplant prophylaxis.
Lifelong PCP prophylaxes.
CMV prophylaxis in D+/R- for 3 months
CMV R +VE to get CMV prophylaxis or surveillance and pr- emptive tx for minimum of 3/12
Assessment of LTBI prior to transplant if pt was not assessed or tx.
Those assessed and tx for LTBI or dx pre transplant not to be reassed unless newly exposed to TB and thereafter managed according ti NICE guidelines for contact tracing.
Lifelong toxo prophylaxis in those with toxoplasmosis IgG +VE recipients.
Ø Aim of the guidelines:
HAART use decreased the mortality from HIV infection. Interest in transplantation in patients with HIV has increased. these guidelines focus on HIV-infected kidney & pancreas transplantation.
Ø Summary of recommendations: Indications for Kidney transplantation recommend that:
• All potential kidney transplant recipients are screened for HIV infection (1D)
• HIV per se is not a contraindication for kidney transplantation (1B)
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been
stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that:
• The most appropriate anti-retroviral therapy is determined before transplantation in
conjunction with an HIV specialist in order to anticipate potential drug interactions and
appropriate dosing of medication (Not graded)
pancreas transplantation: suggest that:
• Diabetic patients in renal failure and with controlled HIV infection are considered for
simultaneous kidney and pancreas transplantation (2D)
• Diabetic patients with severe hypoglycaemic unawareness may be considered for
solitary pancreas or islet transplantation if they have well controlled HIV and kidney
function that is stable and preserved (eGFR >40mL/min) (Not graded) absolute contraindications for transplantation in HIV patients:
1- Uncontrolled HIV infection( CD4 T-cell count >100 last 6 months or persistent detection of HIV RNA during last 3 months
2- incompliance to HAART therapy due to psychiatric issues drug abuse
3- Multi drug-resistant HIV infection
4- Positive CDC cross match
5- Active or disseminated malignancy
6- Serious active infection including hx of PML
7- Pregnancy Relative C/I :
1- Positive FCXM
2- ABO incompatibility
3- Treated malignancy including extracutaneous Kaposi sarcoma
4- CLD
5- Severe uncontrolled medical illness that will not improve with transplantation
6- Marked obesity, BMI >35
7- HTLV infection Pre-transplant immunization :
– HBV vaccine to all non-immunized ( HBV SAb<10 )
– HAV vaccine to all non-immne patients
– Pneumococcal polysaccharide vaccine 23 to all patients
– Varicella zoster vaccine to all non-immune patients with CD4 cell count >200.
– Influenza vaccine annually to all patients in the waiting list.
– DTP suggested being given to all patients
– MMR vaccine suggested being given to all non-immune to measles
– HPV vaccine is recommended to all at risk of HPV acquisition.
Consideration to drug-drug interaction:
– Recommend continuing HAART perioperatively
– Suggest that pre-imperative switching away from protease inhibitors-based therapy, if alternatives exist, to minimize the interaction.
– Refer to Liverpool HIV drug interaction resource. Induction & maintenance immunosuppression :
– Use of interleukin -2 receptor antagonist for induction in most of the HIV-positive patients.
– For maintenance, use of triple steroid+CNIs+antiproliferatives
– Acute rejection treated as in HIV-negative patients.
Post transplant prophylaxis:
– Lifelong prophylaxis against pneumococcal pneumonia.
– Prophylaxis against CMV for 3 months in CMV – ve recipients from CMV +ve donors.
– Assessment of latent TB infection & disease if not done before transplantation
– Life-long prophylaxis against toxoplasma, if ig G positive with CD4 <200 or recipient from donor seropositive toxoplasmosis/
– Prophylaxis of mycobacterium avium complex if cd4<50 & stop if cd4>100 for 6 months
Monitoring of HIV virological control:
– HIV RNA & CD4 count after one month, then every 2-3 months for the 1st year, then every 3-6 months thereafter. ( could be done more frequently if the use of lymphocyte-depleting agents)
– If persistent HIV viremia exists, drug resistance testing is carried out.
Living vs deceased donors:
– Same access to living donor kidney transplantation as non-infected patients
– HIV infected are not suitable to be living kidney Donors. Consent & Confidentiality:
– Standard consent as the same for any other transplant.
– the recipient is encouraged to disclose their diagnosis of HIV to their donor
– All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV Use of HIV-infected donors for HIV-infected recipients:
– Restricted to deceased donors with 1- HIV viral load <50 persistently for 6 months prior to brain injury
2- no hx of virological failure or drug resistance
– Recipients should be counselled & consented with all information.
1.Kidney & Pancreas Transplantation in Patients with HIV
Please summarise this article
Introduction
The mortality rate of HIV patients deceased recently when introduced HAART in 1996.but morbidity is increased which is related to chronic conditions related to kidneys,liver , heart.
HIV patients are risky for chronic kidney disease ,ESRD and hemodialysis there for the transplantation is increased . Indications for Kidney transplantation Waiting list for kidney transplantation
1.They are concordant with treatment, particularly cART therapy (1D)
2. Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
3.HIV RNA has been undetectable during the previous 6 months (1B)
4. No opportunistic infections have occurred during the previous 6 months (1B)
5.They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B) Suggestion
The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded) Indications for Pancreas Transplantation
Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded) Suggestion
Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded) Contraindications to transplantation absolute contraindications:
1.Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
2.psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
3.Multi-drug resistant HIV infection that cannot be controlled with currently available anti retroviral therapy (ART) (1D)
4. Positive complement-dependent cytotoxic (CDC) crossmatch (1D) e) Serious ongoing or recurring infection, including documented history of PML (1D)
5. Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D) 6.Pregnancy (1D). relative contraindications to kidney transplantation
1. Positive flow cytometric crossmatch (FCXM) (1D)
2. Blood-type incompatibility (2D)
3. Treated malignancy, including extra cutaneous Kaposi sarcoma (2C)
4. Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
5. Chronic liver disease (2D)
6. Marked obesity (BMI >35 kg/m2) (2D) g) HTLV infection (1D) HIV-specific assessment
All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
Recommendation against
1.Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
2.Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)related lymphoma (1D) Suggestion In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded)
Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D)
Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may beconsidered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D) Pancreas assessment
Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C) Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded) The assessment of pancreas transplantation in HIV by:
1.Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy)
2. Vascular assessment (ultrasound assessment of leg vessels, and consider noncontrast CT of aorta and iliac arteries)
3.Consideration of a more extensive cardiac assessment (2C) The immunization pre transplantation by :
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B) Suggestion in immunization
Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D)
Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C) drug-drug interactions
Continuation of antiretroviral therapy in the perioperative period following transplantation (1D) Suggestion for drug –drug interactions
• A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (Not graded) Induction and maintenance immunosuppression
All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C).
Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D) Post-transplant prophylaxis
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C)
Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D) Monitoring allograft function
Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
Local practice for monitoring of the pancreas allograft is followed (Not graded) Monitoring of HIV virological control
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D) Choice of living versus deceased donor
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
Patients with HIV infection are unsuitable to be living kidney donors (1D) Consent and confidentiality
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded) All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded) HIV-infected donors for HIV-infected recipients
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with: a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury Information about the donor virus such as historical genotype patterns where possible and current viral load .
No history of virological failure or drug resistance (1D)
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
Patients with HIV-infection are unsuitable to be living kidney donors (1D)
HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
1- BTS Guidelines for renal transplantation in HIV patient:
Indication for kidney transplantation:
All potential kidney transplant recipients are screened for HIV infection.
HIV per se is not a contraindication for kidney transplantation (1B)
HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been
stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma.
Contraindication to transplantation:
Absolute:
1- Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during
the last 6 months and HIV RNA persistently detectable during the last 3 months.
2- Habitual and irremediable non-concordance.
3- Multi-drug resistant HIV infection.
4- Positive CDC cross match.
5- serious onging or recurrent infection including PML
6- Active Malignancy
7- pregnancy.
Relative:
1- Positive FCXM
2- ABO incompatibility
3- Treated malignancy including extra-cutaneous Kaposi.
4- severe or uncontrolled medical condition
5- chronic liver disease
6- Obesity (BMI>35)
7- HTLV infection
General assessment:
• All transplant candidates undergo careful immuno-virological and antiretroviral status
review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral
therapies, HLA-B5701 status and HIV resistance profile.
• Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid
organ transplantation if otherwise well and fully adherent with their medications.
• Transplant candidates undergo screning:
serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii
tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test. If positive, should be evaluated for active TB. pre-transplant treatment of latent or active TB.
Viral hepatitis screening: HBs Ag and HCVab. if positive RNA is recommended.
Transplant candidates from endemic regions are screened for Strongyloides stercoralis
infection prior to transplantation
cervical and anal neoplasia and treated first.
Transplantation is not recommended in:
-liver cirrhosis or active HCV infection.
-history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary
effusion lymphoma or Epstein-Barr virus (EBV)-elated lymphoma
Antiretrovirals with nephrotoxic potential ( tenofovir and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available
Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation.
Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions.
Pre-transplant immunization:
Recommended vaccination:
HBV and HAV in non-immune patient.
pneumococcal polysaccharide vaccine
VZV in non-immune with CD4<200/ml
influenza vaccine annually.
Suggested vaccines:
DTP for all patient
MMR in non-immune for rubella
HPV vaccine.
Induction and maintenance IS:
All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation with an interleukin-2 receptor antagonist (IL-2RA)
triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent.
Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients.
Post transplant prophylaxis:
lifelong prophylaxis against Pneumocystis pneumonia following transplantation.
CMV prophylaxis for a minimum 3 months.
Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/μL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis.
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/μL, and it be stopped when the CD4 count is >100 cells/μL for 6 months.
Monitoring of HIV viral control:
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter.
If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options.
Living vs diseased donor:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients.
Patients with HIV infection are unsuitable to be living kidney donors.
Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory.
Use of HIV-infected donors for HIV-infected recipients
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
1- HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to
brain injury
2- Information about the donor virus such as historical genotype patterns where
possible and current viral load
3- No history of virological failure or drug resistance.
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation
Patients with HIV-infection are unsuitable to be living kidney donors
Introduction
o This is a BTS guidelines (Kidney & Pancreas Transplantation in Patients with HIV), March 2015 [Minor Revision January 2017]
o UK guidelines recommend that combination antiretroviral therapy (cART) be provided to all patients with CD4 cell counts of <350 cells/µL (87% achieved viral suppression)
o With current cART, we can expect a near-normal life expectancy
o HIV-associated nephropathy (HIVAN) is the commonest cause of ESRD in HIV-positive patients in the UK
o HIV infection is not associated with an increased risk of diabetes mellitus per se but drugs (indinavir, lopinavir/ritonavir, stavudine, zidovudine and didanosine) may be associated with greater disturbances of glucose homeostasis
HIVAN:
o Black are at increased risk
o Typically young (mean age 36 years)
o With severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median eGFR] 21 mL/min/1.73m2) at diagnosis
o Majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
Indications of kidney transplantation
o In carefully selected HIV-positive patients, patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation
o Some studies report a high acute rejection rates (is >50%). The explanation is unclear, although immunological, pharmacological, and racial factors seem to have a role
o The most appropriate anti-retroviral therapy for an individual patient should be discussed with the HIV/infectious disease team before transplantation
o Integrase inhibitors do not inhibit the P-450 (limited experience of the use in patients with ESKD, and, reduced absorption if co-prescribed with phosphate binders)
Recommendation states We recommend that all potential kidney transplant recipients are screened for HIV infection (1D) We recommend that HIV per se is not a contraindication for kidney transplantation (1B) We recommend that HIV-positive patients are wait-listed only if:
1. They are concordant with treatment, particularly cART therapy (1D)
2. Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
3. HIV RNA has been undetectable during the previous 6 months (1B)
4. No opportunistic infections have occurred during the previous 6 months (1B)
5. They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B) We suggest that the most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
Indications of pancreas transplantation Recommendation states We recommend that potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded) We suggest that diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D) We suggest that diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded)
Contraindications to transplantation Infections considered contraindications to transplantation:
1. Deep and persistent infections or infections with resistant bacteria and fungi [empyema, Aspergillus infection and colonization, infection with other invasive fungi, and infection with Methicillin-resistant Staphylococcus aureus (MRSA) or Vancomycin-resistant Enterococcus (VRE)]
2. Untreated active chronic infections (active CMV and mycobacterial infection, unless there is clear evidence of successful treatment)
3. Progressive multifocal leukoencephalopathy (PML), which is a rare and usually fatal viral disease caused by a polyomavirus and occurs almost exclusively in people with severe immune deficiency
4. Self-limiting infections within the last 30 days where there is a significant risk of reactivation with immunosuppressive therapy [influenza or respiratory syncytial virus (RSV)]
Recommendation states We recommend that the following are absolute contraindications to kidney transplantation in patients with HIV
1. Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
2. Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
3. Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
4. Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
5. Serious ongoing or recurring infection, including documented history of PML (1D)
6. Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
7. Pregnancy (1D)
We suggest that the following are relative contraindications to kidney transplantation
1. Positive flow cytometric crossmatch (FCXM) (1D)
2. Blood-type incompatibility (2D)
3. Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
4. Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
5. Chronic liver disease (2D)
6. Marked obesity (BMI >35 kg/m2) (2D) g) HTLV infection (1D)
General assessment Recommendation states We recommend that existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded)
HIV-specific assessment Additional objectives from an HIV perspective:
1. To ensure infectious complications post-transplantation are minimised through screening, immunisation and/or the provision of treatment
2. To formulate a management plan that allows the safe co-administration of combination antiretroviral therapy (cART) and immunosuppression
o The appropriate cART regimen for patients awaiting SOT is determined by the presence of HIV resistance mutations and the recipient’s ability to tolerate specific antiretrovirals
o Thymidine analogues (stavudine and zidovudine) and didanosine should be avoided
o Non-nucleoside reverse transcriptase and integrase inhibitors have a minimal or no drug-drug interactions with immunosuppressants
o Ritonavir- (or cobicistat-) boosted protease or integrase inhibitors require careful adjustment of especially calcineurin-inhibitors
o Tenofovir disoproxil fumarate and atazanavir are associated with kidney injury and kidney disease progression (should be avoided)
Recommendation states We recommend that all transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D) We recommend that patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C) We recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D) We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C) We recommend that transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C) We recommend that transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C) We recommend that transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C) We recommend that all transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C) We recommend that all hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B) We recommend that patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
We recommend against:
1. Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
2. SOT in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)related lymphoma (1D) We suggest that
o In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
o Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded)
o Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D)
o Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
o Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
Pancreas-specific assessment Recommendation states We recommend that:
o Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C)
o Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded) We suggest that:
o Pancreas transplantation assessment in patients with HIV includes: a) Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy)
o Vascular assessment (ultrasound assessment of leg vessels, and consider noncontrast CT of aorta and iliac arteries) c) Consideration of a more extensive cardiac assessment (2C)
Pre-transplant immunization Recommendation states We recommend that:
o Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
o Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
o Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
o Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
o Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B) We suggest that:
o Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
o Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D)
o Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
Consideration of drug-drug interactions
Recommendation states We recommend:
o Continuation of antiretroviral therapy in the perioperative period following transplantation (1D) We suggest:
o A full and current medication review as part of the assessment for sot, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
o A dose-finding trial of calcineurin-inhibitors prior to SOT in order to determine optimum doses to initiate post-transplant (2D)
o Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
o That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
Induction and maintenance immunosuppression Recommendation states We recommend that:
o All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
o For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
o HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C) We suggest that:
o Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis Recommendation state We recommend that:
o HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
o Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
o CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
o Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
o Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
o Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C) We suggest that:
o Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
o Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
o Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
Monitoring allograft function Recommendation states We recommend that:
o Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded) We suggest that:
o Local practice for monitoring of the pancreas allograft is followed (Not graded)
Monitoring of HIV virological control Recommendation states We recommend that:
o Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
o If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D) We suggest that:
o More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living versus deceased donor Recommendation states We recommend that:
o Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
o Patients with HIV infection are unsuitable to be living kidney donors (1D) We suggest that:
o Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality Recommendation states We recommend that:
o Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
o The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
o Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded) We suggest that:
o Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
o All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
o All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
o All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
Use of HIV-infected donors for HIV-infected recipients Recommendation states We recommend that:
o Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
b) b) Information about the donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance (1D)
o Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
o Patients with HIV-infection are unsuitable to be living kidney donors (1D) We suggest that:
o HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
BTS Kidney and Pancreas Transplantation in Patients with HIV Summary of the Article Indications for kidney transplantation We recommend that
All potential kidney transplant recipients are screened for HIV infection (1D)
HIV per se is not a contraindication for kidney transplantation (1B)
HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D) b) Their CD4+ T cell count is > 100 cells/microL (ideally > 200 cells/microL) and has been stable the previous 3 months (1B) c) HIV RNA has been undetectable during the previous 6 months (1B) d) No opportunistic infections have occurred during the previous 6 months (1B) e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B) We suggest
The most appropriate ART is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
Indications for Pancreas Transplantation We recommend that
Potential HIV +ve pancreas transplant recipients are assessed by a center with experience in kidney transplantation in HIV+ve patients, and also in the solitary pancreas or islet transplantation (Not graded)
We suggest that
Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Diabetic patients with severe hypoglycemia unawareness may be considered for solitary pancreas or islet transplantation if they have well-controlled HIV and kidney function that is stable and preserved (eGFR > 40 mL/min) (Not graded)
Contraindications to transplantation We recommend that
The following are absolute CI to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently < 100 cells/microL during the last 6 months and HIV RNA persistently detectable during the previous 3 months) (1C) b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems, or persistent substance abuse (1D) c) Multi-drug resistance HIV infection that can not be controlled with currently available ART (1D) d) Positive complement-dependent cytotoxic crossmatch (1D) e) Serious ongoing or recurring infection, including a documented history of PML (1D) f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D) g) Pregnancy (1D) HIV specific assessment We recommend
Careful immuno-virological and AR status review (CD4 cell count, HIV RNA, Current or prior ART, HLA-B5701 status, and HIV resistance profile (1D)
HIV RNA < 200 copies/mL is suitable for SOT if otherwise well and adherent to treatment (1C)
Serological test for syphilis, HSV, EBV, CMV, VZV, T-cell leukemia, and toxoplasma gondii (1D)
Mycobacterium latent TB infection by an interferon-gamma with or without a concurrent Mantoux test strategy for immunocompromised patients in the current NICE TB guidelines (1C)
Positive test for M.TB should be assessed for evidence of active TB(1C)
Evident active or latent TB patients should be treated according to the NICE guidelines prior to Tx (1C)
Those with positive HB or HC infection should have HB DNA or HC RNA and the presence of cirrhosis (1C)
HBsAg +ve should receive HB treatment to ensure DNA level is fully suppressed (1B)
We recommend against
Patients with liver cirrhosis (1B)
Patient with evidence of HCV replication (1C)
Patients with a history of Castleman’s disease, HZV8-related primary effusion, or EBV-related lymphoma (1D)
We suggest that
ART with nephrotoxic potential (tenofovir and atazanavir) should be avoided if suitable alternatives are available (Not graded)
ART with significant CNIs interaction (ritonavir and cobicistat) should be avoided if suitable alternatives are available (2D)
Tx candidates in endemic regions should be screened for Strangyloides stercoralis infection prior to Tx (2D)
Anti-HBc +ve alone recipients do not require routine AR prophylaxis against HBV reactivation but may be considered in those with a risk of reactivation (2D)
Pancreas-specific assessment We recommend that
Assessment should be done in an experienced center in renal and pancreas transplantation (1C)
Transplant candidates should be counseled about a little experience of pancreas transplantation in HIV-related patients (Not graded)
We suggest that
Pancreas Tx assessment in patients with HIV include
a) Diabetic assessment (hypoglycemia unawareness, peripheral neuropathy, and autonomic neuropathy) b) Vascular assessment (US leg vessels, and contrast CT of the aorta and iliac arteries. c) Consideration of extensive cardiac assessment (2C) Pre-transplant immunisation
We recommend that
HBV vaccine for all non-immune patients with HBsAb titer < 10 mIU/mL (1B)
HAV vaccine should be administered to all non-immune patients (1D)
PPV-23 is administered to all patients (1B)
VZV vaccine is administered to all non-immune patients with CD4 cell counts >200 cells/ml (1C)
Influenza vaccine administered annually to all patients waiting for SOT (1B)
We suggest that
DTP vaccine administered to all patients (2D)
MMR should be administered to all patients who are non-immune to measles (2D)
HPV vaccine is offered to patients at risk of HPV acquisition (2C)
Consideration of drug-drug interactions We recommend
Continuation of ART in the perioperative period following Tx (1D)
We suggest
Therapeutic review and to be repeated at least twice yearly and at every therapeutic decision point (Not graded)
A dose-finding trial of CNIs prior to Tx to determine the optimum doses to initiate post-Tx (2D)
Pre-emptive switching from boosted PI-based ART, if an alternative exists, in order to minimize drug interactions (2D)
Induction and maintenance immunosuppression We recommend that
All HIV patient candidates for Tx should be offered induction therapy at the time of Tx (1C)
For the majority of HIV-positive patients, induction therapy is with an IL-2RA (1B)
HIV-positive patients are given triple therapy (steroids, CNIs, and antiproliferative agents (1C)
We suggest that
Acute rejection in HIV-positive Tx should be treated as HIV-negative Tx (2D)
Post Tx prophylaxis We recommend that
HIV-positive Tx recipients receive lifelong prophylaxis against pneumocystis pneumonia following Tx (1D)
Prophylaxis against CMV seronegative recipients of organs from donors with seropositive CMV for a minimum of months (1A)
Tx patients who are not assessed and treated for M. TB latent infection or disease before Tx should be assessed as recommended for patients prior to Tx (1C)
Tx recipient who is well assessed and treated from latent M.TB should not be assessed unless new exposure to mycobacterium (1C)
Tx patient who is re-exposed to TB after Tx should be M.TB latent infection and/or disease as recommended in current TB guidelines (1C)
We suggest that
Toxoplasma IgG seropositive recipients with a CD4 count < 200 cells/ml or any recipients of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
Prophylaxis against M. avium complex MAC is indicated when CD4 count </ 50 cells/micro/L , and to stop when CD$ count become >100 cells/micro/L for 6 months (2D)
Monitor allograft function We recommend that
Exciting guidelines for post-operative period care of the kidney Tx should be offered to all Tx with HIV disease (Not graded)
Monitor HIV virological control We recommend that
Quantitative HIV RNA and CD4 T-cell counts are measured regularly after 1 month after Tx, 2-3 months during the first year, and 3-6 months thereafter (1B)
If the patient develops persistent HIV viremia, drug-resistance testing should be done to determine treatment option (1D)
We suggest that
More frequent CD4 counts should be done in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living vs deceased donor We recommend that
Patients with HIV infection have the same access to Tx as the non-infected patients (1B)
Patients with HIV infection are unsuitable for living donation (1D)
We suggest
Patients donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality We recommend that
Existing guidelines for ethics of deceased and living donor Tx are followed for all Tx involving people with HIV disease (Not graded)
The standard consent for HIV+ve candidate Tx is the same as for any other Tx (Not graded)
We suggest that
Wherever possible the recipients with HIV + ve are encouraged to disclose their diagnosis of HIV to their donor (Not graded)
All living donors should be asked about any medical conditions that may change their mind about donation without highlighting HIV (Not graded)
All donors should be informed that some recipient’s media; and social issues may be disclosed (Not graded).
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney Tx (Not graded)
Use of HIV-infection donors for HIV-infected recipients We recommend that
Transplantation using HIV-infected individuals is restricted to organs from deceased donors with;
a) HIV viral load <50 copies and CD4 count >200 for at least 6 months prior to brain injury. b) Information about the donor virus such as historical genotype patterns where possible and current viral load. c) No history of virological failure or drug resistance (1D)
Recipients are counseled and give informed consent both at the time of listing and Tx (1D)
Patients with HIV infection is not suitable for living donation (1D)
We suggest that
HIV + organ use is restricted to those centers that have experience in Tx HIV+ patients (Not graded)
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Summarize this article I Recommendations & suggestions: Indications for kidney transplantation Recommendations:
· Screening for HIV is mandatory for all recipients (1D)
· HIV is not a contraindication for kidney transplantation
· HIV-positive patient is considered for transplantation when they are compliant with Cart treatment (1D), stable CD4 count > 100 over the last 3 months (1B), undetectable viral load & absence of opportunistic infections over the last 6 months, Absence of lymphoma. Suggestions
· HIV specialist should be involved in the management before proceeding to transplantation
Indication for pancreas Transplantation Recommendation
· HIV positive recipient should be evaluated in a center with experience in transplanting HIV positive patients
Suggestions
· Consider simultaneous kidney and pancreatic transplantation in diabetic, HIV and ESKD (2D)
· Severe hypoglycemic unawareness in diabetic, HIV, and stable CKD (eGFR > 40 ml/min) can be listed for either solitary pancreas or islet cell transplantation (not graded) General assessment
· This should follow the same guideline for non-HIV recipients (not graded) HIV-specific assessment Recommendations
· Check CD4 count, viral load, HLA-b5701, & HIV resistance profile (1D)
· Tests for syphilis, HSV, EBV, CMV, VZT, Toxoplasma gondii (1D)
· Evaluate for latent TB by IGRA and rule out active TB in those with positive results (1D)
· Treat latent or active TB according to NICE guidelines before proceeding to transplantation
· Screening for viral hepatitis is mandatory (1C)
· Those who are discovered to have HBV should treated before transplantation to the point of viral suppression (1B). liver cirrhosis is a contraindication for transplantation (1B) as well as active HCV infection (1C)
· Screening for anogenital cancer should be carried out for all candidates (1D) Suggestions
· Transplantation may be considered in special situation when the patient is virally suppressed & CD4 count is < 200 but > 100 cells/microliter (2C)
· Avoid ARVs such as TDF and atazanavir if possible due to potential risk of nephrotoxicity (not graded)
· Avoid ARVs with significant drug -drug interactions with CNIs (ritonavir & cobicistat) whenever possible (2D)
· Screening for strongyloides steroralis in endemic areas before transplantation (2D)
· Recipient with only anti-HBc Ab is low risk and may not requires antiviral prophylaxis unless they had received lymphodepleting induction therapy
Pancreas-specific assessment Recommendation
· All recipients should be evaluated in center with experience in HIV & pancreatic transplantation (1C)
· Patients must be informed & educated that, the experience in these areas is very limited (not graded)
Suggestions
· Consider diabetic (hypoglycemia unawareness, neuropathy), vascular (e.g., PVD, non-contrast CT of the aorta & iliac vessels), & cardiac assessments
Pre-transplant immunization
Recommendations
1. HBV vaccine for those with HBVsAb < 10 mIU/ml (1B)
· Review treatment at least twice yearly (not graded)
· Try to find the optimal dose of CNIs by giving the drug before transplantation (2D)
· Reduce drug -drug interaction by avoiding boosted Pi ARVs whenever possible (2D)
Induction & maintenance immune suppression
Recommendations
· Induction treatment is to be given to all HIV patients (1C)
· IL-2RA is the standard for most HIV patients (1B)
· Triple immune suppression for maintenance is not different from non-HIV population (1C)
Suggestions
· Treatment of rejection is similar to non-HIV population (2D)
Posttransplant prophylaxis
Recommendations
· Prophylaxis against PCP is for life (1D)
· CMV prophylaxis is not different from the general population (1A)
· Evaluate for LTB or active TB before transplantation (1C)
· Re-evaluate should be done for those who are re-exposed to TB after transplantation according to NICE guideline (1C)
Suggestions
· Toxoplasma IgG positive recipients with CD4 < 100 or any recipient of toxoplasma positive donor organ should be given prophylaxis for life time (2C)
· Prophylaxis against MAC is indicated when CD4 is < 50 and to be stop when CD4 is > 100 for at least 6 months (2D)
Monitoring of allograft function
Recommendations
· Follow the same guidelines for the general population (not graded)
Suggestions
· Follow practice guidelines for pancreas allograft (not graded)
Monitoring of HIV virus control
Recommendations
· HIV PCR should be done 1 month after transplantation then every 2 to 3 months for the first year & 3 to 6 months after the first year (1B)
· Order HIV-drug resistance profile in cases of HIV viraemia (1D)
Suggestions
· Consider CD4 monitoring for patient who received lymphodepleting agents (2D)
Choice of living versus deceased donor
Recommendations
· Access to living donor kidney transplantation should be the same as the general population (1B)
· HIV infected person is suitable as a living donor (1D)
Suggestion
· Donors may be informed the potential risk for the recipients but the disclosure of the HIV status is not mandatory (not graded)
Consent and confidentiality
Recommendations
· Follow the same ethical guidelines for the non-HIV individuals (not graded)
Suggestions
· The recipients may be encouraged to disclose their status to their donors if that is possible (not graded)
· Donors should be in told that, the medical & social information of their recipients are confidential (not graded)
Use of HIV-infected donors for HIV-infected recipients
Recommendations
· This is only in deceased donor set up and the donor must fulfil the following criteria: 1. HIV viral load < 50, and CD4 > 200 for at least 6 months before brain death, 2. Information about the virus is available, 3. No history of drug resistance (1D)
· The recipient must be counselled at the time of enlisting and at the time of transplantation (1D)
· HIV positive person is not suitable as a living donor (1D)
Suggestions
· Transplantation of HIV positive organs should be left for centers which have the experience for HIV positive transplantation (not graded)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate your emphasis on ‘equity of distribution’ of donor organs irrespective of prospective recipient’s HIV status.
The introduction of HAART medication in 1996 has reduced the incidence of morbidity and mortality associated with HIV disease. However, as these medications are prolonging their life, it is also giving rise to diseases associated with aging of which CKD take a dominant role among patient living with HIV. Moreover, because of increased cardiovascular risk among those using dialysis as a form of renal replacement therapy, there has been a growing interest in kidney transplantation among patients with HIV.
In light of this, BTS has made the following recommendation for the optimal outcome for HIV patients undergoing kidney transplantation.
Indication for kidney transplantation
All potential kidney transplant recipients are screened for HIV infection
HIV per se is not a contraindication for kidney transplantation
HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy
b) CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of PML, intestinal cryptosporidiosis, or lymphoma.
Absolute contraindication to kidney transplant
Persistently detected CD4 T-cell count <100cell/um in the last 6 months and persistently detectable HIV RNA level in the last 3 months
Habitual and irremediable non-concordance, due to major psychiatric disease, irresolvable psychosocial problems, or persistent substance abuse
Multi-drug resistant HIV infection that is uncontrolled with the current available ART
Positive CDC crossmatch
Serious ongoing or recurring infection, including a documented history of PML
Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer
Pregnancy
Relative contraindication to kidney transplantation
Positive flow cytometric crossmatch (FCXM)
Blood-type incompatibility
Treated malignancy, including extracutaneous Kaposi sarcoma
Severe and/or uncontrolled medical problems that may not improve after kidney transplantation and will reduce the patient’s life expectancy
e) Chronic liver disease
Marked obesity (BMI >35 kg/m2 )
HTLV infection
HIV specific assessment
Transplant candidates undergo serology tests for syphilis, CMV, EBV, Herpes simplex virus, varicella-zoster virus, Toxoplasma gondii, human T-cell leukemia virus
Test for latent TB using IGRA, and if positive, then evaluate for active TB and treated according to NICE guideline
All patients are screened for viral hepatitis
Induction and maintenance of immunosuppression
For the majority of HIV-positive patients, induction therapy is with an interleukin-2 receptor antagonist (IL-2RA)
HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI), and an anti-proliferative agent
Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients
Post- transplant prophylaxis
Lifelong prophylaxis against Pneumocystis pneumonia after transplantation
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months
CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months
Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays 1 month after transplant and subsequent studies every 2-3 months for the first year and then every 3-6 months subsequently.
Living versus diseased donor
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients. Patients with HIV infection are unsuitable to be living kidney donors (1D)
Use of HIV-infected donors for HIV-infected recipients
HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury b)
Information about the donor virus such as historical genotype patterns where possible and current viral load c)
No history of virological failure or drug resistance (1D) •
Recipients are counseled and give informed consent both at the time of listing and at the time of transplantation
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney & Pancreas Transplantation in Patients with HIV, BTS, second edition 2015
Indications for Kidney transplantation:
Screen all KTR for HIV infection (1D)
HIV is not a contraindication for KTx (1B)
HIV-positive patients are wait-listed only if:
a) Commenced on cART therapy and adherent with treatment (1D)
b) Stable CD4+ T count in the past 3 months >100 cells/μL (ideally > 200 cells/ μL) (1B)
c) Undetectable HIV RNA in last 6 months (1B)
d) No opportunistic infections in last 6 months (1B)
e) No previous PML, chronic intestinal cryptosporidiosis, or lymphoma (1B) Suggestions:
cART to be discussed and determined before KT (Not graded)
Indications for Pancreas Transplantation:
Recommend that diabetic HIV patients with controlled infection and in renal failure are candidates for simultaneous kidney and pancreas transplantation (2D).
Recommend that diabetic HIV patients may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and their kidney function is stable at eGFR >40mL/min.
If they have severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if kidney function is stable. (Not graded)
Pancreas recipients should be assessed in center expert in KT for HIV-positive patients, and in pancreas or islet transplantation (Not graded)
Absolute Contraindications to transplantation:
a) Uncontrolled HIV infection; persistently CD4+ <100 cells/μL in last 6 m and persistent HIV RNA detectable in last 3 months (1C)
b) Habitual and irremediable non-concordance with treatment due to major psychiatric disease or persistent substance abuse. (1D)
c) multi-drug resistant HIV infection. (1D)
d) Positive CDC crossmatch (1D)
e) Serious ongoing or recurring infection PML (1D)
f) Malignancy (active or disseminated) (1D)
g) Pregnancy (1D)
Relative contraindications to kidney transplantation:
a) Positive FCXM (1D)
b) ABOi (2D)
c) Treated malignancy; including Kaposi sarcoma (2C)
d) Uncontrolled medical problems (2D)
e) Sever Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D) General assessment: Recommended to follow existing guidelines for all candidate with HIV disease (Not graded) HIV-specific assessment: Should performed in experience center with HIV patients.
Evaluate virological and cART status; CD4 cell count, HIV RNA level, resistance profile and cART history (1D)
If HIV RNA <200 copies/mL, considered Tx if fully adherent with medications (1C)
Serology for syphilis, HSV, EBV, CMV, VZV, HTCLV, Toxoplasma gondii & Strongyloides stercoralis (1D) TB screening & treatment prior to Tx (active and LTBI); with IGRA +/- TST (1C)
Screened for viral hepatitis; If serology positive to confirm with NAT and to look for cirrhosis (1C)
HBsAg positive patients to receive treatment and ensure viral suppression (1B)
Screen & treat for cervical and/or anal neoplasia (1D)
SOT can be considered if HIV RNA suppressed & CD4 < 200 but >100 cells/μL (2C)
Avoid antiretrovirals with nephrotoxic potential or drug-drug interactions.
Anti-HBc positive “alone” recipients do not require prophylaxis unless reactivation risk is high. Pre-transplant immunization:
HBV vaccine to all patients if HBVsAb <10 mIU/mL (1B)
HAV vaccine (for non-immune) (1D)
PPV-23 (1B)
VZV vaccine (non-immune) with CD4 >200 cells/μL (1C)
Influenza vaccine annually (1B) DTP to all patients (2D)
MMR (nonimmune) (2D)
HPV for high risk (2C) Consideration of drug-drug interactions:
Recommended to consider cART in the perioperative period (1D)
Medication review as part of the assessment (Not graded)
CNI trials to determine optimum doses (2D)
Switching from PI regimens to minimize drug interactions (2D) Induction and maintenance immunosuppression:
Induction therapy offered to All KTR with HIV-positive at time of Tx1C)
Induction therapy is with IL-2RA (1B)
Triple maintenance IS started at the time of kidney transplantation Acute rejection is treated the same way as HIV-negative KTR (2D) Post-Transplant Prophylaxis:
lifelong prophylaxis against PCP (1D)
CMV prophylaxis; if CMV R-/ D+ for of 3 months (1A)
Recipient CMV positive; either prophylaxis or surveillance and pre-emptive therapy for 3 mo(1A)
Assess and treat LTBI prior to transplantation, revaluate if new exposure history or symptoms develop, and treat as per NICE guidelines (1C)
Toxoplasma lifelong prophylaxis if either donor is positive or recipient positive & CD4 <200 (2C)
MAC prophylaxis; if CD4 count ≤ 50. To be stopped when the count is >100 cells/μL for 6 months (2D)
Monitoring allograft function:
Follow the current guidelines for post-operative care of the KTR (Not graded) Monitoring virological control:
Post-Tx regular measurement of: HIV RNA and CD4+ T-cell counts, at 1 month then q 2-3 months for the first year then every 3-6 months (1B), more frequent if receiving antibody depleting to assess the need for prophylaxis (2D)
If viremia persistent HIV, test for drug-resistance (1D) Choice of living versus deceased donor:
Access to living donor KT should be the same as non-infected patients. (1B)
HIV donors are unsuitable for donation (1D)
Disclosure of the recipient’s HIV status is not mandatory (Not graded) Consent and confidentiality:
Follow the current guidelines on the ethics for all donors (Not graded)
Donor consent should be adequate and transparent and established in advance (Not graded)
Encourage the recipient to disclose HIV diagnosis to their donor (Not graded)
Donors are asked about any condition cause them to change their decision to donate, without highlighting HIV (Not graded)
Donors should be aware about that medical and social or confidential information about the recipient that is not disclosed (Not graded) Use of HIV-infected donors for HIV-infected recipients:
Using HIV-infected organs is restricted to organs from DD with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Genotype patterns where possible and current viral load c) No virological failure or drug resistance (1D)
Recipients are counselled and give informed consent (1D)
LD with HIV-infection are considered for donation (1D)
The use of HIV+ organ is restricted to experience centers
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney transplantation indications
It is recommended that:
• Possible renal transplant recipients have to be screened for HIV infection
• HIV by itself, is not a contraindication for renal transplantation
• HIV-positive patients are wait-listed only if
v they are applicable to receive c ART
v CD4+ T cell counts >100 cells/µL (best >200 cells/uL) and is stable within the last 3 months
v HIV RNA is undetectable within the last 6 months
v No opportunistic infections detected within the last 6 months
v Cases without progressive multifocal leukoencephalopathy (PML), chronic intestinal cryptosporidiosis, or lymphoma histories
It suggested that the suitable anti-retroviral therapy need to be detected pre transplantation with an HIV specialist consultation to notify possible drug interactions and proper dosing of medications. Pancreas Transplantation indications
It is recommended that
· Possible HIV positive pancreas transplant recipients need to be evaluated by an experienced centre in kidney transplantation for HIV-positive patients, also in solitary pancreas or islet transplantation.
It is suggested that diabetic patients having renal failure and controlled HIV infection can be assessed for simultaneous kidney and pancreas transplantation .
Also diabetic patients with unrecognition of severe hypoglycaemia , well controlled HIV and stable kidney function can be included for solitary pancreas or islet transplantation . Transplantation contraindication
In HIV cases ,renal transplantation is absolutely contraindicated if
T HIV infection isn’t under control
T Habitual and untreatable non-concordance
T Multi-drug resistant uncontrolled HIV infection
T Positive CDC crossmatch
T Severe occurring or recurrent infection as PML
T Active malignancy that is treated , metastasizing cancer, disseminated or untreated cancer
T Pregnancy
It was suggested that relative contraindications for kidney transplantation are
ü Positive FCXM
ü ABO incompatibility
ü Treated malignancy
ü Severe uncontrollable medical problems
ü Chronic liver disease
ü Marked obesity
ü HTLV infection General assessment
It is recommended that current guidelines for assessment, choosing and preparation of the possible recipients are the same as that for recipients with HIV disease. HIV-specific assessment
It isrecommended that
• Transplant candidates need precise immuno-virological and antiretroviral status evaluation as CD4 cell count, HIV RNA level, present and previous antiretroviral treatments, HLA-B5701 status and HIV resistance profile.
· Cases having HIV RNA levels <200 copies/mL can be suitable for transplantation if all other issues are in acceptable range.
• Transplant candidates need serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma .
• Transplant candidates are tested for latent TB infection with
an interferon-gamma test with or without Mantoux test as per the strategy of testing in immunocompromised cases in the current NICE Tuberculosis Guidelines.
· Transplant candidates who are positive for latent TB infection
are evaluated for active TB.
• Those with active TB disease are treated as current NICE guidelines before transplantation
· Transplant candidates with latent TB infection, without active
disease are treated for latent TB infection as per NICE TB guidelines, before transplantation
• All transplant candidates are screened for viral hepatitis. Cases with HBsAg or HCV Ab positive need to undergo testing for HBV DNA and HCV RNA levels and evaluated for liver cirrhosis
· HBs Ag positive patients on waiting list for SOT need to be treated to confirm HBV DNA is cured
· Candidates for SOT are evaluated for the presence of cervical and/or anal neoplasia; cases having advanced cervical/anal intraepithelial neoplasia or carcinoma in situ must be treated before transplantation.
It was advised against
· Kidney and/or pancreas transplantation in cases having liver cirrhosis and in cases having active HCV replication
• SOT in cases with history of Castleman’s disease, (HHV8)-related primary effusion lymphoma or (EBV)-related lymphoma
It is suggested that
· In certain cases, SOT can be suitable for cases with fully
suppressed HIV RNA and a CD4 cell count <200 cells/µL but >100 cells/µL
• Antiretrovirals with nephrotoxic potential are avoided in renal transplantation if proper substitutes are available
· Antiretrovirals with drug-drug interactions with CNI (ritonavir
and cobicistat) are avoided in SOT if proper the setting of solid alternatives are available .
• Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection before transplantation
· HBc Ab positive only recipients (donor negative, recipient sAg and DNA negative) do not need routine antiviral prophylaxis but it can be donein cases with increased risk of reactivation Pancreas-specific assessment
It is recommend that
· Possible transplant recipients evaluation need to be carried out in a centre that is experienced in renal transplantation in HIV patients and experienced in pancreas transplantation
· Transplant candidates need to be precisely counselled and informed that the present experience of pancreas transplantation in HIV-infected patients is not much.
It is suggested that
• Pancreas transplantation evaluation in HIV cases involves diabetic , vascular and cardiac assessment Pre-transplant immunisation
It is recommend to
• administer Hepatitis B virus (HBV) vaccine to all non-immune patients (HBV sAb titres <10 mIU/mL)
• administer Hepatitis A virus (HAV) vaccine to all non-immune cases
•administer Pneumococcal polysaccharide vaccine (PPV-23) to all cases
• administer Varicella zoster vaccine (VZV) vaccine to non-immune cases with CD4 cell counts >200 cells/µL
• administer Influenza vaccine to patients on SOT waiting list
It is suggest to
• give DPT to all cases
• give MMR vaccine to all patients nonimmune to measles
• offer HPV vaccine to patients at risk of HPV acquisition Drug-drug interactions consideration
It is advised to maintain antiretroviral therapy in perioperative period after transplantation.
It is suggested
· for evaluation of SOT to do full medical review and repeat it at least twice yearly afterwards.
· To do CNI dose finding trial before SOT to know the optimum doses started after transplantion
· Preventive avoidance boosted protease-inhibitors (PI)-based antiretroviral regimens, if substitutes ae there exist, to decrease drug interactions
· Liverpool HIV Drug Interactions Resource can be used Induction and maintenance immunosuppression
It is advised that:
• All HIV-positive patients considered for renal transplantation to be offered induction therapy at transplantation time which is interleukin-2 receptor antagonist for most cases
• HIV-positive cases can take triple immunosuppressive maintenance therapy at kidney transplantation time , including steroids ,CNI and anti-proliferative agent
It is suggested to:
• treat acute rejection in HIV-positive kidney transplant recipients the same as treating HIV-negative kidney transplant recipients Post-transplant prophylaxis
It is advised to
• administer lifelong prophylaxis against Pneumocystis pneumonia in HIV-positive transplant recipients post transplantation
•give prophylaxis against CMV for CMV seronegative recipients receiving organs from CMV seropositive donors at least for 3 months
• give prophylaxis against CMV infection or do PCR surveillance and pre-emptive treatment for at least 3 months to CMV seropositive transplant recipients
· Transplant recipients asymptomatic and not evaluated and treated for latent or active TB infection have to be assessed before transplantation as per guidelines
· Transplant recipients asymptomatic and evaluated and treated for latent or active TB infection before transplantation donot need reassessment for latent TB expect if there is history of new exposure
· Re-exposure of recipients to tuberculosis post transplantation need evaluation for TB latent infection and/or disease as recommended in NICE TB guidelines
It is suggested that:
• Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or recipients from a donor seropositive for toxoplasmosis need to receive lifelong prophylaxis.
• When there is dependable previous history of treated TB infection it is unneeded to do more tests also those cases do not need TB prophylaxis except if TB re-exposure is doubted .
• Prophylaxis against Mycobacterium avium complex (MAC) is needed when the CD4+ count is ≤ 50 cells/µL, and it can be terminated when the CD4 count is >100 cells/µL for 6 months Monitoring allograft function
It is advised to follow current guidelines for post-operative care of the kidney transplant recipient for recipients with HIV disease
It is suggested to follow local practice for monitoring of the pancreas allograft Monitoring of HIV virological control
It is recommend to
• measure quantitative HIV RNA and CD4+ T-cell counts regularly, starting 1 month after transplant and thereafter every 2-3 months for the first year then every 3-6 months
• For cases with HIV viraemia, drug-resistance testing is needed to determine treatment options.
It is suggested that
• frequent monitoring of CD4 count will be needed in patients receiving depleting antibodies to notice the need for anti-infective prophylaxis Choice of living versus deceased donor
It is recommend that:
• HIV infected cases should have the same access to living donor kidney transplantation as non-infected patients
• HIV infected cases are unsuitable to be living kidney donors
It is suggested that:
• Possible donors for HIV infected cases have to be informed of medical, surgical, and psychosocial factors that can affect the recipient’s morbidity and mortality risk but disclosing the recipient’s HIV status is not a must Consent and confidentiality
It is recommend that:
• guidelines on the ethics of deceased donor and living donor transplantation need to be followed for all transplantation including those with HIV disease and the same standard of consent
• Transplant teams must guarantee the adequacy of donor consent and the transparency of procedures in advance
It is suggested that
· the recipient is encouraged to inform their diagnosis of HIV to their donors
· the donor must be asked if there is any medical disease that can let them reject donation without saying it is HIV also donors have to be informed that there is a medical condition the recipient has but is unrevealed
· living donors need to be acknowledged that they are aware that confidential data concerning the recipient won’t be told to them Use of HIV-infected donors for HIV-infected recipients
It is recommend that:
· Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
-HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months before brain injur
-Information about the donor virus such as historical genotype and viral load
-No history of drug resistance
· Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
· Patients with HIV-infection cannot be living kidney donors
It is suggested that HIV+ organ transplant to be carried out only in centres that have experience in transplanting HIV+ cases
All potential recipients should screened for HIV infection
HIV not contraindication for transplantation.
HIV patients enrolled to waiting list if:
adherent to antiretroviral
Cd4 count >100 & stable over 3 months.
undetectable HIV viral load.
no opportunistic infection during previous 6 months
no history of PML, chronic intestinal cryptospordiosis or lymphoma.
Post transplant ART determination by HIV specialist.
Indications of pancreatic transplant & HIV:
Any patient with HIV & planned for pancreatic transplantation should be assessed in kidney transplant center with experience of HIV.
ESRD & DM with HIV considered for simultaneous transplantation.
Patient with DM & unawareness of severe hypoglycemia & GFR >40, isolated pancreatic or islet transplant indicated if HIV infection is controlled.
Contraindication for transplantation:
(A) Absolute:
uncontrolled HIV infection.
habitual & irremediable non adherence e.g. major psychological disease, unresolvable psychological problem or drug abuse.
multi-drug resistant HIV infection can’t be controlled by available ART.
postive CDC
serious infection, documented PML
active malignancy under treatment, metastatic cancer, disseminated untreated cancer.
pregnancy.
(B) Relative:
ABO incompatibility.
positive FXCM
treated malignancy including extracutaneous Kaposi sarcoma
severe &/or uncontrolled medical disease unlikely to improved after transplant.
CLD
BMI>35.
HTLV infection
Potential recipient assessment:
All patients follow same steps as patient with out HIV infection, in addition to:
CD4 count, HIV RNA, ART HLA-B570 status.
CD4 count<200 & adherent to treatment can proceed to transplantation.
test for syphilis, HSV, EBV, CMV, VZV, HTLV & toxoplasma for all patients.
Latent TB screened by INF-gama test with or without TST(treatment of latent & active TB according NICE TB guidelines
All patient screened for HBV, if HBsAg positive or HCVAb positive should be tested for DNA/RNA with screening of liver diseases. In HBsAg patients on waiting list should b treated to ensure suppressed HBV DNA.
screening for cervical &/or anal cancer, any patient with CIN/AIN III or carcinoma in situ should be receive treatment before transplant
Kidney &/or pancreatic transplant not recommended in patients with liver cirrhosis & evidence of active HCV replication.
Any patient history of Castleman disease, HHV8-related lymphoma or EBV-related lymphoma should discourage from transplantation.
Some patients with suppressed HIV RNA & CD4<200>100 can offered for SOT.
Nephrotoxic drugs & ART have drug interaction with immunosuppression better to be avoided after transplantation & use suitable alternatives.
In endemic area screening of Strongyloidosis is recommended before transplantation.
HBcAb +ve(HBsAg-ve, DNA undetected) not need prophylactic unless lymphodepletion drugs used.
Pancreatic transplant specific assessment:
diabetic status assessment( hypoglycemia awareness, peripheral neuropathy & autonomic neuropathy).
Vascular assessment.
extensive cardiac assessment.
Pre-transplant immunization:
HBV & HAV vaccine for non immune recipients
Pneumococal polysaccharide for all patients.
Yearly influenza virus
DTP for all patients & MMR for non immune patients
VZV for non immune patient & CD4 count>200.
Drug interaction:
Review of all & current ART during SOT assessment.
Dose finding trial of CNI before SOT to determine optimum dose.
Pre-emptive switch from PI based antiviral to reduce drug interaction.
All HIV patients offered kidney transplant use induction with IL-2RA at time of transplantation.
All patient maintenance therapy with CNI,MMF & steroid & rejection episodes treated as in non HIV patients.
Life long PCP prophylaxis
CMV D+/R- prophylactic for 3months & if R+ use prophylactic or follow with PCR for 3 months.
TB screened post transplant if not screened before transplant or if there is history of recent TB exposure.
MAC prophylaxis indicated if CD4 count <50 & stopped when CD4 count>100 for at least 6 months.
Monitoring of HIV virology control:
HIV RNA & CD4 tested at 1month post transplant, 2-3month in first year & 3-6 months then after.
In patients with persistent viremia, drug resistant should be tested.
Patient receive depleted agent need more frequent CD4 count monitoring.
Live vs deceased HIV donors:
HIV+ patients have same access to live donor kidney transplant as non HIV patients, but HIV patient are unsuitable as live donor.
informing live donor about medical, surgical & psychological factor may affect morbidity & mortality of recipients, but informing risk of HIV status not mandatory.
Consent & confidentiality:
Ethics of deceased & live donor transplant followed for all HIV patient involved in transplantation, & standard consent for HiV patient is same for any transplant.
Encourage recipients to disclose their HV status to their donor.
All living donor asked about any medical condition can preclude donation without highlight HIV.
All living donor may be aware of medical & social information of recipients are not disclosed & all donors asked to not give confidential information about recipients.
All potential kidney transplant recipients are screened for HIV infection
HIV per se is not a contraindication for kidney transplantation
HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months
(c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
(e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication
Contraindications to transplantation
Absolute contraindications
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART
e) Serious ongoing or recurring infection, including documented history of PML
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer
g) Pregnancy
Relative contraindications:
a) Positive flow cytometric crossmatch (FCXM)
b) Blood-type incompatibility
c) Treated malignancy, including extracutaneous Kaposi sarcoma
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy
e) Chronic liver disease
f) Marked obesity (BMI >35 kg/m2)
g) HTLV infection
General assessment:
Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease
HIV-specific assessment
All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile
Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications
Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii
Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines
Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease
Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation
Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation
All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis
All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed
Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation
Recommendation against:
Kidney and/or pancreas transplantation in patients with liver cirrhosis and in those with evidence of active HCV replication
Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)-related lymphoma
We suggest that:
In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL
Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available
Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available
Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation
Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy)
Pre-transplant immunisation
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL)
Hepatitis A virus (HAV) vaccine is administered to all non-immune patients Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL
Influenza vaccine is administered annually to patients awaiting solid organ transplantation
Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients
Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles
Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition
Consideration of drug-drug interactions
Continuation of antiretroviral therapy in the perioperative period following transplantation
A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point
A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions
Induction and maintenance immunosuppression
All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation
For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA)
HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent
Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients
Post-transplant prophylaxis
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months
CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing
Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis
Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months
Monitoring allograft function
Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease
Monitoring of HIV virological control
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter
If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options
More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis
Choice of living versus deceased donor
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients
Patients with HIV infection are unsuitable to be living kidney donors
Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory
Consent and confidentiality
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant
Transplant teams must be satisfied that donor consent is adequate and that procedure for ensuring this are transparent and established in advance
Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor
All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV
All living donors are made aware that there may be medical and social information about the recipient that is not disclosed
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant
Use of HIV-infected donors for HIV-infected recipients
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
Information about the donor virus such as historical genotype patterns where possible and current viral load
No history of virological failure or drug resistance
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation
Patients with HIV-infection are unsuitable to be living kidney donors
HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients
Kidney & Pancreas Transplantation in Patients with HIV, BTS, second edition 2015
Indications for Kidney transplantation
· HIV is not a contraindication for kidney transplantation. HIV-positive patients are wait-listed only if:
· They are adherent with treatment.
· Their CD4+ T cell counts are >100 cells/µL and stable during the previous 3 months.
· Negative HIV RNA level during the previous 6 months.
· No opportunistic infections during the previous 6 months.
· No history of progressive multifocal leukoencephalopathy or lymphoma. Indications for Pancreas Transplantation
· It is suggested that diabetic HIV patients with controlled infection and in renal failure are candidates for simultaneous kidney and pancreas transplantation.
· It is suggested that diabetic HIV patients may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and their kidney function is stable at eGFR >40mL/min. Absolute Contraindications to transplantation
· Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months.
· Non-concordance due to major psychiatric disease or persistent substance abuse.
· Multi-drug resistant HIV infection.
· Serious ongoing or recurring infection.
· Active malignancy.
· Positive CDC crossmatch.
· Pregnancy Relative contraindications to kidney transplantation
· Positive FCXM
· Blood group incompatibility
· Treated malignancy
· Severe chronic liver disease, Marked obesity, HTLV infection HIV-specific assessment It is recommended that:
· HIV transplant candidate should have their CD4 cell count and HIV RNA level carefully assessed and monitored.
· They should be tested for syphilis, HSV, EBV, CMV VZV, HTL virus and Toxoplasma gondii.
· Also tested for latent TBI with an IGRA test.
· Transplant candidates with latent TBI, should be treated prior to transplantation.
· All transplant candidates are screened for viral hepatitis. If found to be HBs Ag positive or HCV antibody positive should be assed and treated according to current guideline.
Pre-transplant vaccination include:
· HBV and HAV vaccine
· Pneumococcal polysaccharide vaccine
· VZV vaccine is administered to patients with CD4 cell counts >200 cells/µL
· Influenza vaccine
Induction and maintenance immunosuppression
· All HIV-positive transplant candidate should be offered induction therapy at the time of transplantation with IL-2RA
· HIV-positive patients should be given triple therapy maintenance immunosuppression.
· AR can be treated in the same way as HIV-negative kidney transplant recipients. Post-transplant prophylaxis
HIV positive patients should receive:
· Lifelong pneumocystis pneumonia prophylaxis.
· CMV prophylaxis is indicated in CMV negative recipients if donor is CMV positive.
· If CMV seropositive transplant recipients should receive either prophylaxis, or PCR observation and pre-emptive therapy for CMV.
· Transplant patients who are re-exposed to TB after transplantation should be assessed for latent infection and/or disease.
· Prophylaxis against MAC may be given, when the CD4+ count is ≤ 50 cells/µL, and stopped when the CD4 count is >100 cells/µL for 6 months.
Monitoring kidney function post transplantation
· Should follow the existing guidelines
Monitoring of HIV virology
· Quantitative HIV RNA and CD4+ T-cell counts should be measured at 1 month after transplant and every 2-3 months for the first year then every 3-6 months.
· If persistent HIV viraemia, drug-resistance testing should be performed.
Choice of living versus deceased donor
· Patients with HIV infection are candidates for living donor kidney transplantation as non-infected patients but are considered unsuitable.
Consent and confidentiality
· In HIV-positive transplant candidates you should follow the standard of consent as for any other transplant candidate.
· All living donors should be aware that there may be confidential information about the recipient (not relevant to the transplant outcome) which are not disclosed.
· If possible, the recipient is asked to disclose their diagnosis of HIV to their donors.
Use of HIV-infected donors for HIV-infected recipients
· Patients with HIV-infection are unsuitable for living kidney donation.
· Deceased donors should have HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury.
· If possible Information such as genotype and current viral load should be obtained.
· Should have no history of virological failure or drug resistance.
This article involves recommendations and suggestions regarding kidney and pancreas transplant in HIV patients. The following are updated guidelines with respect to this topic by the British Transplantation Society. The aim is to cover all aspects of assessment, selection and management of HIV positive transplant recipients.
Summary of the main aspects of this article :
Indications for kidney transplant
Although HIV is not an absolute contraindication for kidney transplant, all potential recipients must be screened for HIV.
Wait listing of candidates should follow certain criteria, such as :
Patients who are adherent to therapy, mainly cART therapy
Patient CD4+ T cell counts are below 100 cells/microlitre and have been stable for the past three months
Patient has no detectable HIV RNA in the past 6 months
Patient has no opportunistic infections currently or in the past 6 months
No history of lymphoma or multifocal leukoencephalopathy
Indications for pancreatic transplantation
Patient must be assessed in centre which has experience with HIV positive patients and pancreas or islet transplant
Diabetic patients with renal failure and controlled HIV infection can be considered for simultaneous pancreatic and kidney transplantation.
Contraindications to transplant
Absolute contraindications
Uncontrolled HIV infection with CD4+ T cells less than 100 cells/microlitre in the past 6 months.
Habitual and irremediable non concordance such as persistence substance abuse
Multi drug resistant HIV infection
Positive CDC crossmatch
Current serious or recurring infection
active malignancy
pregnancy
Relative contraindications
Positive FCXM
Blood type incompatibility
Previously treated malignancy including Kaposi sarcoma
Chronic liver disease
Obesity above BMI of 35 kg/m2
HTLV infection
Assessment
Existing guidelines regarding the evaluation, selection, assessment of potential recipients must be followed.
Immunovirological and antiretroviral status review should be done
Serological testing for syphilis, HSV, EBV, CMV, VZV, T cell leukemia virus and toxoplasma gondii must be done
Candidates with evidence of TB must be treated according to current NICE guidelines before the transplant
All candidates must be screened for viral hepatitis, and DNA/RNA quantification must be done, and patient must be assessed for liver cirrhosis.
Ensure that Hepatitis B infection is fully suppressed before the transplant with repeated testing and monitoring with treatment prior to the date of transplant.
Diabetic, vascular and cardiac assessment are crucial for pancreas transplantation.
Immunisation before transplant
HBV and HAV vaccine is to be given to all non immune patients.
PPV 23 vaccine is to be given to all patients.
Influenza vaccine is to be given annually to patients on the waitlist.
BTS suggests DTP and MMR vaccine to all non immune patients.
Immunosuppression and prophylaxis
All eligible patients must be given induction therapy at the time of transplant with IL 2 receptor antagonist
Triple IS regimen is to be followed from the time of kidney transplant, including steroids, CNI and anti-proliferative agent.
Suggested to treat acute rejection in these patients in the same way as non HIV patients
Patients must receive lifelong prophylaxis against Pneumocystis pneumonia post transplant.
CMV prophylaxis is to be given to seronegative recipients receiving organ from seropositive donors.
Donor criteria
HIV infected donor organ can be used provided that the organ is from a deceased donor with no history of virological failure or drug resistance.
Living donors with HIV cannot donate.
Consent
Existing guidelines regarding deceased donor and living donor transplant are to be followed.
Transplant team must be satisfied with donor consent and make sure that the procedures of obtaining consent are transparent and established in advance.
It is suggested that if possible, the recipient is encouraged to disclose HIV diagnosis with donor.
Indications for Kidney transplantation Recommendations:
• Screen all KTR for HIV infection (1D)
• HIV is not a contraindication for KT (1B)
• HIV-positive patients are wait-listed only if:
a) Commenced on cART therapy (1D)
b) Stable CD4+ T count in the past 3 months >100 cells/μL (ideally > 200 cells/ μL) (1B)
c) Undetectable HIV RNA in last 6 months (1B)
d) No opportunistic infections in last 6 months (1B)
e) No previous PML, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Suggestions:
• cART to be discussed and determined before KT (Not graded)
Indications for Pancreas Transplantation Recommendations:
• Pancreas recipients should be assessed in center expert in KT for HIV-positive patients, and also in pancreas or islet transplantation (Not graded)
Suggestions:
Diabetics with controlled HIV can be considered for:
• Simultaneous KPT if they have renal failure (2D)
• if they have severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if kidney function is stable. (Not graded)
Contraindications to transplantation
• Absolute contraindications to KT in patients with HIV:
a) Uncontrolled HIV infection; persistently CD4+ <100 cells/μL in last 6 m & persistent HIV RNA detectable in last 3 months (1C)
b) Habitual and irremediable non-concordance with treatment (1D)
c) Resistance HIV infection to available (1D)
d) Positive CDC crossmatch (1D)
e) Serious ongoing or recurring infection PML (1D)
f) Malignancy( active or disseminated ) (1D)
g) Pregnancy (1D) • Relative contraindications to KT:
a) Positive FCXM (1D)
b) ABOi (2D)
c) Treated malignancy; including Kaposi sarcoma (2C)
d) Uncontrolled medical problems (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
General assessment
• Recommended to follow existing guidelines for all candidate with HIV disease (Not graded)
HIV-specific assessment Recommendations:
• Evaluate virological and cART status; CD4 cell count, HIV RNA level, resistance profile and cART history (1D)
• If HIV RNA <200 copies/mL, considered Tx if fully adherent with medications (1C)
• Serology for syphilis, HSV, EBV, CMV, VZV, HTCLV, Toxoplasma gondii & Strongyloides stercoralis (1D)
• TB screening & treatment prior to Tx ( active and LTBI); with IGRA +/- TST (1C)
• Screened for viral hepatitis; If serology positive to confirm with NAT and to look for cirrhosis (1C)
• HBsAg positive patients to receive treatment and ensure viral suppression (1B)
• Screen & treat for cervical and/or anal neoplasia (1D)
• SOT can be considered if HIV RNA suppressed & CD4 < 200 but >100 cells/μL (2C)
• Avoid antiretrovirals with nephrotoxic potential or drug-drug interactions.
• Anti-HBc positive “alone” recipients do not require prophylaxis unless reactivation risk is high.
Pancreas-specific assessment
• Should performed in experience center with HIV patients.
• Pancreas Tx assessment in patients with HIV includes: detailed diabetic assessment, vascular assessment
& cardiac assessment (2C)
Pre-transplant immunization Recommendation:
• HBV vaccine to all patients if HBVsAb <10 mIU/mL (1B)
• HAV vaccine (for non-immune) (1D)
• PPV-23 (1B)
• VZV vaccine (non-immune ) with CD4 >200 cells/μL (1C)
• Influenza vaccine annually (1B) Suggested:
• DTP to all patients (2D)
• MMR (nonimmune) (2D)
• HPV for high risk (2C)
Consideration of drug-drug interactions
• Recommended to consider cART in the perioperative period (1D)
• Medication review as part of the assessment (Not graded)
• CNI trials to determine optimum doses (2D)
• Switching from PI regimens to minimize drug interactions (2D)
Induction and maintenance immunosuppression
• Induction therapy offered to All KTR with HIV-positive at time of Tx1C)
• Induction therapy is with IL-2RA (1B)
• Triple maintenance IS started at the time of kidney transplantation
• Acute rejection is treated the same way as HIV-negative KTR (2D)
Post-transplant prophylaxis
• lifelong prophylaxis against PCP (1D)
• CMV prophylaxis; if CMV R-/ D+ for of 3 months (1A)
• Recipient CMV positive; either prophylaxis or surveillance and pre-emptive therapy for 3 mo(1A)
• Assess and treat LTBI prior to transplantation, revaluate if new exposure history or symptoms develop, and treat as per NICE guidelines (1C)
• Toxoplasma lifelong prophylaxis if either donor is positive or recipient positive & CD4 <200 (2C)
• MAC prophylaxis; if CD4 count ≤ 50. To be stopped when the count is >100 cells/μL for 6
months (2D)
Monitoring allograft function
• Follow the current guidelines for post-operative care of the KTR (Not graded)
Monitoring virological control
• Post-Tx regular measurement of: HIV RNA and CD4+ T-cell counts, at 1 month then q 2-3 months for the first year then every 3-6 months (1B), more frequent if receiving antibody depleting to assess the need for prophylaxis (2D)
• If viremia persistent HIV, test for drug-resistance (1D) Choice of living versus deceased donor
• Access to living donor KT should be the same as non-infected patients. (1B)
• HIV donors are unsuitable for donation (1D)
• Disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality
• Follow the current guidelines on the ethics for all donors (Not graded)
• Donor consent should be adequate and transparent and established in advance (Not graded)
• Encourage the recipient to disclose HIV diagnosis to their donor (Not graded)
• Donors are asked about any condition cause them to change their decision to donate, without highlighting HIV (Not graded)
• Donors should be aware about that medical and social or confidential information about the recipient that is not disclosed (Not graded)
Use of HIV-infected donors for HIV-infected recipients
• Using HIV-infected organs is restricted to organs from DD with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to
brain injury
b) Genotype patterns where possible and current viral load
c) No virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent (1D)
• LD with HIV-infection are considered for donation (1D)
• The use of HIV+ organ is restricted to experience centers (Not graded)
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
This is a British protocol with the strategy of carrying out a systematic review to define protocols and guidelines for patients living with the HIV virus who are going to undergo a kidney-pancreas transplant or just the first one.
Indications for Kidney Transplantation
Recommendations:
– Everyone should be screened for HIV
– In isolation, it is no longer contraindicated
– Must have a negative viral load for six months, CD4 count greater than 100 (ideally above 200) for three months, no opportunistic infections in the last six months, and no history of PML, lymphoma, or intestinal infection by Cryptosporidium.
Suggestive
Prior evaluation by an infectologist to choose the ideal HAART and its interactions
Indications for pancreas transplantation
– It is recommended to be in a center with experience in HIV patients and kidney transplantation
– It is suggested that for diabetic patients the transplant is associated with the kidney
Contraindications to transplantation
– Uncontrolled HIV infection
– Major psychiatric illness
– Multiple resistance in HIV Genotyping and low availability of medications
– CDC positive
– Pregnancy
– Active malignant disease
Relative contraindications
– positive FCXM
– ABOi
– Kaposi’s sarcoma
– Uncontrollable illness with difficulty in recovery
– chronic liver disease
– BMI greater than 35
– Coinfection with the HTLV virus
Related to HIV
– Frequent measurement of CD4 levels and viral load
– Other serologies should be performed, including latent tuberculosis
– If IGRA positive, proceed with an investigation for active tuberculosis
– Serologies for Hepatitis B and C
– Investigation of cervical/anal neoplasia
Contraindication
– Transplantation in patients with liver cirrhosis or hepatitis C virus replication
– Castleman disease or EBV or HHV8 lymphomas
Suggestions
– Some cases consider CD4 above 100 as applicable to transplantation
– Avoid nephrotoxic antiretroviral formulations
– Evaluate drug interactions with immunosuppressants
Pre-transplant immunization
– HBV vaccine if HbAb < 10mIU/mL
– HAV vaccine if negative serology
– PPV-23 and Influenza
– VZV vaccine if CD4 more than 200 cells
– Consider DPTa, MMR and HPV
immunosuppression
– All HIV-positive patients should undergo induction, if possible with IL2RA
– Triple scheme is the most suitable Tacrolimus + MMF + Prednisone
– Treat acute rejection similarly to non-HIV patients
Prophylaxis
– Pneumocystosis for life (includes toxoplasmosis)
– CMV for three months (prophylaxis or pre-emptive)
– latent tuberculosis
– Mycobacterium avium if CD4 count less than 50 cells
HIV-positive patients have similar access to the donation waiting list. If there is a donation between a donor and recipient positive for HIV, there is a need for extensive investigation and both have no history of resistance to antiretrovirals.
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Contraindications to transplantation
• The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
■ Transplant candidates who test positive for latent TB are assessed for any evidence of active tuberculosis disease (1C)
■ Transplant candidates with evidence of active tuberculosis disease are treated prior to transplantation (1C)
◇All transplant candidates are screened for viral hepatitis.
◇Those found to be HBsA or HCV antibody positive should have their HBV DNA / HCV RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
◇Anti-HBc positive “alone” recipients (donor negative), do not require routine antiviral prophylaxis (2D)
♧ Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; treatment prior to transplantation (1D)
●SoT may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
● Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided if suitable alternatives are available (Not graded)
●Antiretrovirals with significant drug-drug interactions with cNI (ritonavir and cobicistat) are avoided if suitable alternatives are available (2D)
Induction and maintenance immunosuppression
• For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• HIV-positive patients are given triple therapy maintenance immunosuppression
• Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
♤CMV R (NEG ) FROM D (POS) ==> for a minimum of 3 months
♤CMV R (POS) ==> either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months
♤TB re-exposed after transplantation ==> should be assessed for latent infection and/or disease as recommended in current NICE TB guidance
♤Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL ==> lifelong prophylaxis
♤donor seropositive for toxoplasmosis ==> recipient lifelong prophylaxis
♤Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
Monitoring allograft function
• Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
Monitoring of HIV virological control
Quantitative HIV RNA and CD4+ T-cell counts:
○ the first assays at 1 month after ○transplant subsequent every 2-3 months for the first year
○ every 3-6 months thereafter
However, More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies
Choice of living versus deceased donor
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D)
Consent and confidentiality
• Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
• All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
Use of HIV-infected donors for HIV-infected recipients
: • Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
b) Information about the donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
• HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney & Pancreas Transplantation in Patients with HIV
Summary
HIV infection is not a contraindication for kidney transplantation but screening is
mandatory for all potential recipients
:HIV-positive patients are wait-listed only in the following situations
Have CD4+ T cell counts >100 cells/µL –
Have been stable during the previous 3 month –
Have undetectable HIV RNA –
Have no opportunistic infections –
-Have no history of progressive multifocal leukoencephalopathy, chronic intest –
cryptosporidiosis, or lymphoma.
It is suggested that antiretroviral therapy needs to be appropriately determined before transplantation to anticipate potential drug interaction
Indications for Pancreas Transplantation:
Potential HIV positive pancreas transplant recipients should be assessed by a centre with experience in kidney transplantation in HIV-positive patients and also in solitary
pancreas or islet transplantation
Diabetic patients in renal failure and with controlled HIV infection may be considered for
simultaneous or solitary pancreas transplantation, as long as they have stable and preserved eGFR >40mL/min
Contraindications to kidney transplantation in patients with HIV include:
Uncontrolled HIV infection, multi-drug resistant HIV infection , habitual and irremediable non-concordance,, positive complement-dependent cytotoxic (CDC) crossmatch, serious ongoing or recurring infection, active malignancy under treatment, metastatic or untreated cancer, pregnancy, and chronic liver disease.
Relative contraindications include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection.
General assessment
All potential transplant recipients with HIV disease should undergo HIV-specific assessment including careful immunological assessment and antiretroviral status review, plus screening of all possible expected bacterial ,viral ,parasitic and fungal infections .
All transplant candidates should be screened for viral hepatitis, and those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B and C DNA tested.
Solid organ transplantation is recommended for all hepatitis B surface antigen positive patients who are waiting listed for solid organ transplantation.
It is also recommended for those with liver cirrhosis, cervical and/or anal neoplasia, advanced cervical/anal intraepithelial neoplasia (CIN/AIN III), carcinoma in situ, and Epstein-Barr virus (EBV)-related lymphoma to be treated before transplantation .
In selected cases, it may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL, antiretrovirals with nephrotoxic potential are avoided in the setting of kidney transplantation if suitable alternatives are available.
Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation.
Anti-HBc positive “alone” recipients do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk.
Pancreas-specific assessment
Pancreas-specific assessment in HIV-infected patients should be performed in a centre that regularly performs renal transplantation in HIV patients and also regularly performs pancreas transplantation.
Pre-transplant immunisation should include Hepatitis B virus (HBV) vaccine, Hepatitis A virus (HAV), Pneumococcal polysaccharide vaccine (PPV-23), Varicella zoster vaccine (VZV), Influenza vaccine, Diphtheria, tetanus and pertussis (DTP) vaccine, Measles, mumps and rubella (MMR) vaccine, and Human papilloma virus (HPV) vaccine for patients at risk of HPV acquisition.
Consideration of drug-drug interactions
Afull and current medication review for solid organ transplantation is recommended , a dose-finding trial of calcineurin-inhibitors prior to transplantation, pre-emptive switching away from PI-based antiretroviral regimens, and a footer referring practitioners to the Liverpool HIV Drug Interactions Resource.
Induction and maintenance immunosuppression
All HIV-positive patients eligible for kidney transplantation are offered induction therapy with an interleukin-2 receptor antagonist (IL-2RA) and triple therapy maintenance immunosuppression.
Acute rejection is treated in the same way as HIV-negative kidney transplant recipients, and post-transplant prophylaxis is recommended.
Post-transplant prophylaxis
HIV-positive transplant recipients should be assessed for Mycobacterium tuberculosis latent infection and/or disease before transplantation, and reassessed after transplantation.
PCP prophylaxis is life long as well as toxoplasma prophylaxis in case of positive donors ,while CMV prophylaxis in seronegative patients should be for a minimum of 3 months.
Monitoring allograft function:
Monitoring allograft function and HIV virological control is recommended for kidney transplant recipients with HIV disease.
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, and drug-resistance testing is carried out to determine treatment options.
More frequent monitoring of CD4 count may be necessary in patients receiving depleted antibodies to determine the need for anti-infective prophylaxis.
Choice of living versus deceased donor:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients without disclosure of the recipient’s HIV status ,but potential donors are informed of medical, surgical, and psychological factors that may increase the recipient’s morbidity and mortality risk.
Consent and confidentiality:
All potential kidney donors with HIV disease are transplanted following existing guidelines on the ethics of deceased donor and living donor transplantation.
In HIV-positive transplant candidates the consent for kidney transplant is the same as for any other kidney recipient .
Donors should be asked if there are any medical conditions that could change their decision to donate, and be aware of any medical and social information that may not be disclosed.
The recipient is encouraged to disclose their diagnosis of HIV to their donor wherever possible.
Use of HIV-infected donors for HIV-infected recipients:
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury.
Recipients are counselled and given informed consent, and HIV+ organ use is restricted to centres with experience in transplanting HIV+patients.
I. Kidney & Pancreas Transplantation in Patients with HIV Please summarize this article.
Indications for KTX Recommendations:
• The HIV status of all KTX candidates is checked. (1D)
• HIV does not preclude KTX. (1B)
• HIV+ve patients are waitlisted only if:
They are on therapy. (1D)
CD4+ T cells >100 cells/μL(ideally > 200). (1B)
HIV RNA undetectable during the past 6 months (1B)
No opportunistic infections in the past 6 months (1B)
No H/O PML, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Suggestions:
• The best HAART is chosen pre-TX so as to foresee drug interactions & select the right dosages. (Not graded)
===================== Indications for Pancreas Transplantation Recommendations:
• A center with experience in both solitary pancreas or islet TX & KTX in HIV+ve patients evaluates potential HIV +ve pancreas TX recipients. (Not graded) Suggestions:
• SKP TX is an option for diabetic patients with renal failure & treated HIV infection. (2D)
• If a diabetic patient’s HIV is under control & renal function is stable (eGFR >40mL/min), a single pancreas or islet TX may be considered. (Not graded)
===================== Contraindications to transplantation Recommendations: • Absolute contraindications:
Uncontrolled infection (CD4+ T cell <100 cells/μL (last 6 months) & persistent HIV RNA (last 3 months) (1C)
Major psychiatric disease, severe psychosocial issues, or substance abuse (1D)
HIV infection that is MDR & untreatable with HAART (1D)
Positive CDC crossmatch (1D)
Serious persistent or recurrent infection, including PML (1D)
Metastatic & active cancer (1D)
Pregnancy (1D)
Suggestions:
• Relative contraindications:
Positive FCXM (1D)
ABOi (2D)
Treated malignancy, including extracutaneous KS (2C)
Life expectancy shortened by conditions that will not improve post-KTX. (2D)
CLD (2D)
BMI >35 kg/m2 (2D)
HTLV infection (1D)
===================== General assessment Recommendations:
• Adherence to the current standards for evaluation, selection, & preparation of the TX recipient. (Not graded)
===================== HIV-specific assessment Recommendations:
• Careful virological & antiretroviral status review (CD4 cell count, HIV RNA level,& HAART, HLA-B5701 status & HIV resistance profile (1D)
• If HIV RNA levels <200 copies/mL, SOT TX is possible if otherwise well & adherent with medications (1C)
• Serologic testing for syphilis, HSV, EBV, CMV, VZV, HTLV, & Toxoplasma gondii is performed. (1D)
• According to NICE guidelines, TX candidates are screened for latent MBT with an interferon-gamma test +/- Mantoux test. (1C)
• Latent MTB+ve candidates are examined for signs of active TB. (1C)
• Active TB disease treated according to current NICE guidance pre-TX. (1C)
• NICE TB recommendations: latent MB infection, after excluding active disease, is treated for before TX. (1C)
• Screened for viral hepatitis: If HBsAg or HCV antibody positive, HBV DNA/HCV RNA levels measured & checked for liver cirrhosis (1C)
• Those with HBsAg on the waiting list for SOT should get therapy to clear HBV DNA completely. (1B)
• Cervical &/or anal neoplasia in patients being considered for SOT is evaluated; advanced neoplasia (CIN/AIN III) or carcinoma treated before TX. (1D) We recommend against:
• Kidney &/or pancreas TX in patients with liver cirrhosis (1B) & in those with evidence of active HCV replication (1C)
• SOT in patients with a H/O Castleman’s disease, HHV8-related primary effusion lymphoma or EBV-related lymphoma (1D) Suggestions:
• Patients with totally suppressed HIV RNA & CD4 cell < 200 cells/L but > 100 cells/L may in some circumstances be candidates for SOT. (2C)
• If acceptable substitutes are available, antiretrovirals with nephrotoxic potential (tenofovir & atazanavir) are avoided. (Not graded)
• If adequate substitutes are available, antiretrovirals with strong drug-drug interactions with CNI (ritonavir & cobicistat) should be avoided. (2D)
• Strongyloides stercoralis infection is checked in candidates from endemic areas. (2D)
• Anti-HBc +ve “alone” recipients (donor -ve, recipient sAg & DNA -ve): routine antiviral prophylaxis not required, but may be considered if increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
===================== Pancreas-specific assessment Recommendations:
• Only centers routinely performing pancreas & KTX in HIV patients should assess such potential TX recipients. (1C)
• Inform TX candidates that there is limited experience of pancreas TX in HIV-infected patients (Not graded) Suggestions:
• Pancreas TX assessment in patients with HIV:
Vascular assessment: US of leg vessels, non-contrast CT of aorta & iliac arteries
Consider a more thorough cardiac evaluation (2C)
===================== Pre-transplant immunization Recommendations:
• HBV vaccine for all non-immune patients (HBV surface antibody <10 mIU/mL) (1B)
• HAV vaccine for all non-immune patients (1D)
• PPV-23 for all patients (1B)
• VZV vaccine for non-immune patients with CD4 cell counts >200 cells/μL (1C)
• Influenza vaccine annually to patients awaiting SOT (1B) Suggestions:
• DDTP vaccine for all patients (2D)
• MMR vaccine for those all non-immune to measles (2D)
• HPV vaccine for at risk patients (2C)
===================== Consideration of drug-drug interactions Recommendations:
• Continue antiretroviral therapy in the perioperative time post-TX (1D) Suggestions:
• A thorough review of all current medications to be done at least twice a year afterward & at each significant therapeutic decision point. (Not graded)
• A dose-finding trial of CNI prior to SOT in order to find an optimum doses to initiate post-TX (2D)
• If alternatives are available, switching from boosted PI-based HAART regimens in advance to minimize medication interactions (2D)
• A footer directing doctors to the Liverpool HIV Drug Interactions Database should appears on all clinical communication (www.hiv-druginteractions.org) (Not graded)
===================== Induction and maintenance immunosuppression Recommendations:
• Induction therapy is provided to all HIV-+ve patients who are eligible for KTX. (1C)
• Induction therapy is with IL-2RA for the majority of HIV +ve patients (1B)
• HIV+ve individuals are given triple therapy maintenance IS (steroids, a CNI, & an anti-proliferative drug). (1C) Suggestions:
• HIV+ve KTX recipients who experience AR are treated similarly to HIV-ve recipients. (2D)
===================== Post-transplant prophylaxis Recommendations:
• HIV-positive TX recipients receive lifetime Pneumocystis pneumonia prevention. (1D)
• In CMV -ve recipients from CMV +ve donors, prophylaxis against CMV is advised for a minimum of 3 months. (1A)
• For a minimum of 3 months, CMV +ve TX recipients receive either prophylaxis against CMV infection or PCR surveillance & preventive medication. (1A)
Patients who are healthy but have not had their MTB latent infection or disease evaluated & treated before TX should do so after TX. (1C)
• Unless there is a new H/O exposure to TB, TX patients who are healthy & were previously diagnosed with & treated for MBT latent infection or illness do not require review for latent infection. (1C)
• NICE TB guidance on TB contact tracing: TX patients who are re-exposed to TB after TX should be evaluated for MBT latent infection &/or disease. (1C) Suggestions:
• Lifelong prophylaxis for any recipient of an organ from a donor positive for toxoplasmosis or who has a toxoplasma IgG serology & a CD4+ count < 200 cells/L. (2C)
• When a previous diagnosis of successfully treated TB is present, only a chest X-ray & symptoms review are required; TB prophylaxis is not necessary unless TB re-exposure is suspected. (2D)
• When CD4+ level is < 50 cells/L, MAC prophylaxis is recommended. It should be discontinued after 6 months if CD4+ count is > 100 cells/L. (2D)
===================== Monitoring allograft function Recommendations:
• Current guidelines for post-operative care of the KTX recipient are followed for all KTX recipients with HIV disease (Not graded) Suggestions:
• Follow local protocol for pancreatic allograft monitoring (Not graded)
===================== Monitoring of HIV virological control Recommendations:
Regular measurements of HIV RNA & CD4+ T-cell counts are made; the initial tests performed 1 month after TX & then every 2-3 months for the first year & every 3-6 months after that. (1B)
• Drug-resistance testing is done on patients with chronic HIV viraemia to assess therapy choices. (1D) Suggestions:
• To evaluate if a patient needs anti-infective prophylaxis while receiving depleting antibodies, more frequent CD4 count monitoring may be required. (2D)
===================== Choice of living versus deceased donor Recommendations:
• HIV-positive patients have the same access to LD KTX as non-infected patients (1B)
• HIV-positive persons are unacceptable as LKDs (1D) Suggestions:
• The medical, surgical, & psychosocial aspects that increase the recipient’s risk of morbidity & mortality are disclosed to potential donors, but not necessarily the recipient’s HIV status. (Not graded)
===================== Consent & confidentiality Recommendations:
• The current standards for LD & DD transplant ethics are adhered to. (Not graded)
• For HIV+ve TX candidates, the same standards of consent apply as for any other TX. (Not graded)
• Methods for obtaining acceptable donor consent should be transparent & pre-established. (Not graded) Suggestions:
• Recipients are urged to inform their donors of their HIV diagnosis whenever feasible. (Not graded)
• Without specifically mentioning HIV, all LDs are asked about any issues that would make them reconsider donating. (Not graded)
• LDs are informed that the recipient’s medical & social history might not be shared. (Not graded)
• LDs should certify that they are aware that they will not be given private information about the recipient that is not thought to be important to the KTX recipient’s prognosis. (Not graded)
===================== Use of HIV-infected donors for HIV-infected recipients Recommendations:
• TX using organs from HIV-infected individuals is restricted to organs from DDs with:
HIV viral load <50 copies/mL & CD4 count >200/μL for at least 6 months prior to brain injury
Details on the donor virus, including, if available, genotyping patterns & present viral load
No virological failure or resistance in the past (1D)
Recipients are counseled & provided with an informed consent document. (1D)
HIV+ve patients are not acceptable as LDs(1D)
Suggestions:
• Only facilities with experience transplanting HIV+ patients are allowed to use HIV+ organs. (Not graded)
I appreciate your very detailed structured summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
BTS Guidelines for Kidney & Pancreas Transplantation in Patients with HIV: Indications for Kidney transplantation:
-All potential kidney transplant recipients are screened for HIV infection. (1D)
-HIV per se is not a contraindication for kidney transplantation. (1B)
-HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy. (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months. (1B)
c) HIV RNA has been undetectable during the previous 6 months. (1B)
d) No opportunistic infections have occurred during the previous 6 months. (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma. (1B) Contraindications to transplantation: The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently < 100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months). (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse. (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART. (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch. (1D)
e) Serious ongoing or recurring infection, including documented history of PML. (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer. (1D)
g) Pregnancy. (1D) The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM). (1D)
b) Blood-type incompatibility. (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma. (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy . (2D)
e) Chronic liver disease. (2D)
f) Marked obesity (BMI >35 kg/m2 ) . (2D)
g) HTLV infection. (1D) General assessment:
-Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease. (Not graded) HIV-specific assessment:
-All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile. (1D)
-Patients with HIV RNA levels < 200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications. (1C)
-Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii. (1D)
-Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines. (1C)
-Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease. (1C)
-Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation. (1C)
-Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation. (1C)
-All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis. (1C)
-All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed. (1B)
-Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation. (1D) Recommendations against:
-Kidney and/or pancreas transplantation in patients with liver cirrhosis, (1B)
and in those with evidence of active HCV replication. (1C)
-Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma. (1D) Pre-transplant immunization:
-Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres < 10 mIU/mL). (1B)
-Hepatitis A virus (HAV) vaccine is administered to all non-immune patients. (1D)
-Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients. (1B)
-Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL. (1C)
-Influenza vaccine is administered annually to patients awaiting solid organ transplantation. (1B) Consideration of drug-drug interactions:
-Continuation of antiretroviral therapy in the perioperative period following transplantation. (1D)
-A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant. (2D)
-Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions. (2D) Induction and maintenance immunosuppression:
-All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation. (1C)
-For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA). (1B)
-HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent. (1C) Post-transplant prophylaxis:
-HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation. (1D)
-Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months. (1A)
-CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months. (1A)
-Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation. (1C)
-Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis. (1C)
-Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing. (1C)
-Toxoplasma IgG seropositive recipients with a CD4+ count < 200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis. (2C)
-Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected. (2D)
-Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months . (2D) Monitoring of HIV virological control:
-Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter. (1B)
-If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options. (1D) Choice of living versus deceased donor:
-Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients. (1B)
-Patients with HIV infection are unsuitable to be living kidney donors. (1D) Consent and confidentiality:
-Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease. (Not graded)
-The standard of consent for HIV-positive transplant candidates is the same as for any other transplant.(Not graded)
-Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance. (Not graded) Use of HIV-infected donors for HIV-infected recipients:
-Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load < 50 copies/mL and CD4 count > 200/µL for at least 6 months prior to brain injury,
b) Information about the donor virus such as historical genotype patterns where possible and current viral load,
c) No history of virological failure or drug resistance. (1D)
-Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation. (1D)
-Patients with HIV-infection are unsuitable to be living kidney donors. (1D).
Yes I like your well structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
We recommend that: All potential kidney transplant recipients are screened for HIV infection.
HIV per se is not a contraindication for kidney transplantation.
HIV-positive patients are wait-listed only if: A) They are concordant with treatment, cART therapy
B) Their CD4+ T cell counts are >100 cells/μL and have been stable during the previous 3 months
C) They have no history of progressive multifocal leukoencephelopathy, chronic intestinal cryptosporidiosis, or lymphoma.
We suggest that: The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication. Indications for pancreas transplantation
Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and in solitary pancreas or islet transplantation.
Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation.
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved.
Contraindications to transplantation
The following are absolute contraindications to kidney transplantation in patients with HIV:
A) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during the last 6 months and HIV RNA persistently detectable during the last 3 months).
B) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse,
C) Multi-drug resistant HIV infection that cannot be controlled with currently available.
D) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy.
E) Serious ongoing or recurring infection, including documented history of PML .
F) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer.
The following are relative contraindications to kidney transplantation: a) Positive flow cytometric crossmatch (FCXM).
General assessment
Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded).
All transplant candidates undergo careful immuno-virological and antiretroviral status review
This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile .
Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications.
Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation.
Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation.
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL).
That all clinical correspondence carries a footer referring practitioners to the Liverpool Induction and maintenance immunosupression
All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation.
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation.
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months.
CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months.
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis.
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing.
Count is ≤ 50 cells/μL, and it be stopped when the CD4 count is >100 cells/μL for 6 months. Monitoring of HIV virological control
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year every 3-6 months thereafter.
If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options.
More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis.
Choice of living versus deceased donor
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients.
Patients with HIV infection are unsuitable to be living kidney donors.
Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory. Consent and confidentiality
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease.
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant .
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance.
Yes I like your well structured detailed summary.
I appreciate that HIV positive recipients are assessed and treated forMycobacterium tuberculosis latent infection.
> All kidney transplant candidates should be HIV-screened (1D)
HIV does not exclude kidney transplantation (1B)
• HIV-positive individuals are wait-listed only if: a) They comply with treatment, especially cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/μL (preferably > 200) and have remained steady for 3 months (1B)
c) HIV RNA was undetectable for 6 months (1B)
d) No opportunistic infections in 6 months (1B)
e) No progressive multifocal leukoencephalopathy, persistent intestinal cryptosporidiosis, or lymphoma history (1B)
Pancreas transplant indications:
• Prospective HIV-positive pancreatic transplant candidates should be evaluated by a center with expertise in kidney and solitary pancreas or islet transplantation (Not graded)
Transplant contraindications
HIV-positive people cannot have kidney transplantation:
a) Uncontrolled HIV infection (CD4+ T cell levels <100 cells/μL for 6 months and HIV RNA for 3 months) (1C)
b) Persistent non-concordance owing to serious mental disorder, psychological issues, or drug addiction (1D)
c) Multi-drug resistant HIV infection uncontrollable with current ART (1D)
CDC crossmatch positive (1D)
e) Chronic infection, with PML history (1D)
f) Treatment-resistant, metastatic, disseminated, or untreated cancer (1D)
pregnancy (1D)
HIV testing:
• All transplant candidates should be carefully immuno-virologically and anti-retrovirally assessed. CD4 cell count, HIV RNA level, current and past antiretroviral treatments, HLA-B5701 status, and HIV resistance profile (1D)
• Individuals with HIV RNA levels <200 copies/mL and good treatment adherence may be eligible for solid organ transplantation (1C)
• Transplant candidates are serologically tested for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human T-cell leukemia virus, and Toxoplasma gondii (1D)
• Transplant candidates are evaluated for latent Mycobacterium TB infection using an interferon-gamma test with or without a Mantoux test according to the NICE Tuberculosis Guidelines for immunocompromised patients (1C)
• Latent Mycobacterium tuberculosis-positive transplant candidates are tested for active illness (1C)
• Active TB patients are treated according to NICE guidelines before transplantation (1C)
• NICE TB guidelines recommend treating latent Mycobacterium tuberculosis infection in transplant candidates who have been cleared of active illness before transplantation (1C)
All transplant candidates undergo viral hepatitis screening. • All hepatitis B surface antigen-positive patients who are waitlisted for solid organ transplantation get therapy to completely suppress hepatitis B DNA (1B)
• Solid organ transplant candidates with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or cancer in situ should be treated before transplantation (1D)
Avoid:
• Kidney and pancreas transplantation for liver cirrhosis (1B) and HCV replication (1C)
• Solid-organ transplantation in Castleman’s illness, HHV8-related primary effusion lymphoma, or EBV-related lymphoma patients (1D)
Pancreas evaluation
• Potential transplant recipients should be assessed at a center that frequently conducts renal and pancreas transplantation in HIV patients (1C)
• Transplant candidates are carefully counseled and advised that HIV-infected patients have minimal pancreatic transplantation experience (Not graded)
Pre-transplant immunization
• All non-immune patients (HBV surface antibody titers <10 mIU/mL) should get the HBV vaccination (1B)
• All non-immune patients get HAV vaccination (1D)
• All patients get PPV-23/pneumococcal polysaccharide vaccination (1B)
Non-immune patients with CD4 cell counts >200 cells/μL get varicella zoster vaccination (VZV) (1C)
Solid organ transplant candidates get influenza vaccination yearly (1B)
• All HIV-positive kidney transplant candidates get induction treatment (1C)
• Most HIV-positive individuals get IL-2RA induction treatment (1B)
• HIV-positive kidney transplant recipients get steroids, a calcineurin inhibitor (CNI), and an anti-proliferative drug for triple treatment immunosuppression (1C)
Post-transplant prophylaxis:
HIV-positive transplant patients get lifetime Pneumocystis pneumonia prevention (1D)
• CMV seronegative recipients of organs from CMV-positive donors should get cytomegalovirus prophylaxis for three months (1A)
• CMV-positive transplant patients get either prophylaxis or PCR monitoring and pre-emptive medication for at least three months (1A)
17
• Healthy transplant patients who were not screened and treated for Mycobacterium TB latent infection or illness before transplantation should be assessed as indicated (1C)
• Healthy transplant patients who were screened and treated for Mycobacterium TB latent infection or illness before transplantation do not require review unless there is a new history of exposure (1C)
• According to current NICE TB guidelines on tuberculosis contact tracing, transplant patients who are re-exposed should be tested for Mycobacterium tuberculosis latent infection and/or illness (1C)
Allograft monitoring;
• HIV-positive kidney transplant patients should follow post-operative care recommendations (Not graded)
HIV virus surveillance:
• Quantitative HIV RNA and CD4+ T-cell counts are assessed at 1 month after transplant and every 2-3 months for the first year, then every 3-6 months after that (1B)
Drug-resistance testing determines therapy choices for individuals with chronic HIV viremia (1D)
Living or deceased donor?
• HIV-positive individuals should have equal access to live donor kidney transplantation (1B)
Consent, confidentiality:
• HIV-positive patients should follow dead donor and live donor transplantation ethical standards (Not graded)
HIV-positive transplant patients must agree like other transplant candidates (Not graded)
• Transplant teams must be certain that donor permission is sufficient and that processes are transparent and predetermined (Not graded)
HIV-infected donor-recipient pairing
• HIV-infected organs should only be transplanted from dead donors.
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Donor virus information, including genotyping patterns and current viral load
c) No virological failure or drug resistance (1D)
• Listers and transplanters are counseled and obtain informed consent (1D)
HIV-positive people cannot donate kidneys (1D)
Yes I like your well structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney & Pancreas Transplantation in Patients with HIV
INDICATIONS FOR KIDNEY TRANSPLANTATION:
Recommendations:
All potential kidney transplant recipients are screened for HIV infection.
HIV per se is not a contraindication for kidney transplantation.
recommend wait-listing HIV patients only if:
a) They are concordant with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/µL (ideally >200 cells/µL) and have been stable during the previous 3 months.
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
We suggest that the most appropriate anti-retroviral therapy for an individual patient should be discussed with the HIV/infectious disease team before transplantation.
The use of anti-retroviral such as integrase inhibitors that do not inhibit the P-450 system may simplify the use of immunosuppressants in this setting and decrease the frequency of rejection however.
NDICATIONS FOR PANCREAS TRANSPLANTATION:
Recommendations:
Suggest that diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation.
suggest that diabetic patients with severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min).
CONTRAINDICATIONS TO TRANSPLANTATION:
Recommendations:
Absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently less than 200cell/micml.
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse.
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART.
d) Positive CDC crossmatch.
e) Serious ongoing or recurring infection, including documented history of PML.
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer.
g) Pregnancy.
Relative contraindications to kidney transplantation:
a) Positive FCXM.
b) Blood-type incompatibility.
c) Treated malignancy, including extra cutaneous Kaposi sarcoma.
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy.
e) Chronic liver disease.
f) Marked obesity (BMI >35 kg/m2).
g) HTLV infection.
HIV-SPECIFIC ASSESSMENT:
Careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile.
Solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL in selected cases, should be full adherent to medication.
Its suggest that antiretroviral with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation so do drug interact with CNI (ritonavir and cobicistat)
Recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukemia virus and Toxoplasma Gondi and T.B plus latent T.B. Also, test for HBC, HCV and Strongyloides stercoralis.
Screen for malignancy:
Cervical smear and rectal examination annually
PANCREAS-SPECIFIC ASSESSMENT:
Recommendations:
We suggest that pancreas transplantation assessment in patients with HIV includes:
• Diabetic assessment (for hypoglycemic unawareness, peripheral neuropathy, & autonomic neuropathy)
• Vascular assessment (ultrasound assessment of leg vessels, and consider non-contrast CT of aorta and iliac arteries)
• Consideration of a more extensive cardiac assessment.
PRE-TRANSPLANT IMMUNISATION:
Recommendations:
• HBV vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B) • Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D) • Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B) • Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL.
HAV vaccine is administered to all non-immune patients.
• Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients.
• VZV vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL.
Suggest that:
• DTP vaccine is administered to all patients
• MMR) vaccine is administered to all patients who are non-immune to measles
• Human papilloma virus vaccine is offered to patients at risk of HPV acquisition.
Influenza vaccine is administered annually to patients awaiting solid organ transplant.
CONSIDERATION OF DRUG-DRUG INTERACTIONS:
Recommendations
A full and current medication review as part of the assessment for solid organ transplantation
On, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant.
Suggest pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimize drug interactions.
Continuation of antiretroviral therapy in the perioperative period following transplantation.
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION:
Induction with (IL-2RA) and MAINTENANCE with triple therapy.
Treatment of acute rejection:
If antibody mediated rejection, consideration of plasma-exchange, anti-CD20 monoclonal antibody or intravenous immunoglobulin, with or without lymphocyte-depleting agents.
POST-TRANSPLANT PROPHYLAXIS:
Recommendations:
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation. The drug of choice for prophylaxis is trimethoprim-sulfamethoxazole (cotrimoxazole) 480 mg once daily. Second line aerosolized pentamidine 300 mg via nebulizer monthly or Dapsone 100 mg once daily. In case of co-trimoxazole or Dapsone allergy, consider Atovaquone 1500 mg once daily or
, lifelong prophylaxis is recommended for Toxoplasma IgG+ subjects with a CD4+ countless than 200 cell/mic ml co-trimoxazole s960 mg once daily is recommended as first line prophylaxis ,although many studies show successful prophylaxis using co-trimoxazole 960 mg thrice weekly for varying durations. An alternative that has been well studied in patients with HIV/AIDS is Dapsone 50 mg once daily plus pyrimethamine 50 mg once weekly.
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3months. Valganciclovir is the preferred prophylactic agent.
Recommend that CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months.
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation.
transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis .
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing.
Treated patient no need for assessment unless there is symptoms or reexposures.
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months.
Non-tuberculosis mycobacteria (NTM):
Among HIV-infected persons, a CD4+ T cell count of less than 50cell s associated with increased risk of disseminated NTM infection. . It is therefore suggested that prophylaxis against NTM is indicated when the CD4+ T cell count is ≤50 /µL, and may be stopped when the CD4+ count has been >100 cells/µL for 6 months.
Prophylaxis is with azithromycin 1250 mg once weekly; alternatively clarithromycin 500 mg twice daily or rifabutin 300 mg once daily.
The preferred secondary prophylaxis is with azithromycin 500 mg once daily in combination with ethambutol 15 mg/kg/day; alternatively, clarithromycin 500 mg twice daily plus ethambutol 15 mg/kg/day.
MONITORING ALLOGRAFT FUNCTION:
Recommendations:
Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease.
MONITORING OF HIV VIROLOGICAL CONTROL:
quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months there t if patients have persistent HIV viremia, drug-resistance testing is carried out to determine treatment options after.
CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients. Those potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory. HIV are not suitable donors.
CONSENT AND CONFIDENTIALITY:
Recommend that existing guidelines on the ethics of deceased donor and living donor transplantation be followed, also consent, encourage recipient to disclose their condition to donors.
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS:
Recommendations:
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
– HIV viral load <50 copies/mL and CD4 count >less than 50copies/ml and CD4 count more 200/µL for at least 6 months prior to brain injury.
– Information about the donor virus such as historical genotype patterns where possible and current viral load –
No history of virological failure or drug resistance
Introduction.
Scope and aim of guidelines;
The aim is to give comprehensive summary guidelines of all aspects of management, prevention, surveillance of the HIV positive transplant recipient.
Indications for kidney transplantation.
Recommendations;
There is no absolute contraindication for trasnpalntation if,
They are complaint with treatment,
No HIV RNA during the last six months.
CD4+T counts >100.
No opportunistic infections.
Suggestions;
Start appropriate dose of HAART therapy.
Indication for Pancreas transplantation.
Recommendations;
Can proceed for transplantation after expert opinion of expert people.
If, there is no such dissiminated malignancy, active chronic or acute active infection.
Relative contraindication if there is incompatibility as it may worsen the prognosis of graft.
General recommendations for HIV specific assessment.
Recipient should be screened for all opportunistic infections, prophylaxes for this, if there is any infection, occult malignancy should be treated before proceeding for transplantation.
Pre-trasnplantation immunization.
HBV, HAV, PPV, VZV, and influenzea vaccination should be done before transplantation.
If CD4+T is >200.
While MMR, DPT, and HPV vaccine are given to all patients.
Choice of living versus deceased donor.
Its suggested that it should be disclosed to recipient HIV status is not graded, and HIV infected have the same access to living and deceased donor.
Please summarise this article.
HIV patients can be listed for Tx if they are stable as follow:
Indications for Pancreas Transplantation with stable HIV:
Contraindication absolute
Uncontrolled HIV infection, persistent low CD4 count and detectable viral load.
Multi-drug resistant uncontrolled HIV infection
Positive complement-dependent cytotoxic (CDC) crossmatch
Serious ongoing or recurring infection, cancer or pregnant
Contraindication relative: CLD, obese, treated Malig, positive flow cytometry and ABO incompatibility
Assessment
Pre-transplant immunisation HAV, HBV, influenza, pneumococcal, VZV, DPT, MMR, HPV
Drugs:
A) ARV
Avoid ARV with nephrotoxic potential ( tenofovir and atazanavir)
Avoid those with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat)
Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org)
B) dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
C) Induction and maintenance immunosuppression
Induction with interleukin-2 receptor antagonist (IL-2RA)
Maintenance with steroid + CNI + antiproliferative
Rejection as non HIV patients
Post-transplant prophylaxis
PCP – life long
CMV – as non HIV
MAC: CD count < 50 and stop if > 100
Toxoplasma: IgG+ve recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor positive receive lifelong prophylaxis
Monitor HIV RNA and CD4 count post transplant
Choice of living versus deceased donor
HIV +ve not suitable for live donation
Use of HIV-infected donors for HIV-infected recipients when donor CD4 count > 200 and viral load < 50 in the past 6M with no hx of virological resistance or failure
Transplantation for HIV positive patient
BTS guideline outlined and recommend the indications and process of kidney transplantation and pancreatic transplantation for HIV infected patients.
This guideline insures stability of the general condition with well controlled HIV reflected as maintained CD4 lymphocyte count of preferably more than 200.
General indications for kidney transplantaion :
1] No contraindications for HIV patients to have transplantation.
2] HIV screening has to be implemented for all transplant candidates.
3] HIV patient may be considered transplant candidate when they are consistent with HIV medications, in particular the combined anti-retroviral therapy cART.
4] A stable CD4 of more than 100-200 which is stable for at least 3 months.
5] Well control of viral replication, reflected by undetected HIV RNA [RNA copies less than 200copies/ml] for 6 months.
6] Cell mediated immunity is intact, reflected by absence of opportunistic infection for at least 6 months, such as serological tests for syphilis, CMV, HSV, varicella zoster, toxoplasma and mycobacterium.
7] Major complications related to HIV infection have to be excluded.
8] No history of Malignancy such as lymphoma.
9] Absence of CNS involvement, particularly, progressive multifocal leukoencephalopathy.
10] Refuting of chronic infection such as intestinal cryptosporidiosis.
Reflecting on the above mentioned indications, certain features were considered by the guideline as absolute or relative contraindications for kidney transplantation, owing to the exceeding risk of adverse clinical outcome.
In summery,
The contraindications for kidney transplantation are:
1] Multidrug resistance HIV.
2] Most importantly, uncontrolled HIV infection demonstrated as
a}CD4 count of less than 100 cell/ml for 6 months.
b}Persistence of blood HIV RNA for 3 months.
3] Noncompliance of the patient with his medications.
4] Malignancy.
5]PLE
Relative contraindications include Obesity with BMI of more than 35 and co-infection with HTLV.
EXECUTIVE SUMMARY OF RECOMMENDATIONS
INDICATIONS FOR KIDNEY TRANSPLANTATION
Recommendations:
• All potential kidney transplant recipients are screened for HIV infection (1D)
• HIV per se is not a contraindication for kidney transplantation (1B)
• HIV-positive patients are wait-listed only if:
– Concordant with treatment, particularly cART therapy (1D)
– CD4+ T cell counts are >200 cells/µL and have been stable during the previous 3 months (1B)
– HIV RNA has been undetectable during last 6 months (1B)
– No opportunistic infections have occurred in last 6 months (1B)
– No h/o progressive multifocal leukoencephalopathy (PML), chronic intestinal cryptosporidiosis, or lymphoma (1B)
Suggestions:
· The most appropriate anti-retroviral therapy (ART) is determined before transplantation in conjunction with an HIV specialist, in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
CONTRAINDICATIONS TO TRANSPLANTATION
Absolute contraindications for kidney transplantation in HIV patients:
a) Uncontrolled HIV infection – (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due to major psychiatric illness, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
Relative contraindications to kidney transplantation in HIV patients
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) ABO-incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) – (2D)
g) HTLV infection (1D)
HIV-SPECIFIC ASSESSMENT
Recommendations:
– All transplant candidates undergo careful immuno-virological and ARV status review, including CD4 cell count, HIV RNA level, current and prior ART, HIV resistance profile and HLA-B57 status. (1D)
Suggestions:
– In selected cases, SOT may be appropriate – if fully suppressed HIV RNA and CD4 T cell count <200 cells/µL but >100 cells/µL. (2C)
– Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
– ARV with nephrotoxic potential (tenofovir and atazanavir) are avoided for patient of kidney transplantation, if suitable alternatives are available (Not graded)
– ARV with significant drug-drug interactions with CNI (ritonavir and cobicistat) are avoided in the setting of SOT, if suitable alternatives are available (2D)
Recommendations:
– Transplant candidates undergo serologic testing for syphilis, HSV, EBV, CMV, HTLV-1, Varicella Zoster virus and Toxoplasma gondii (1D)
– Transplant candidates are tested for latent TB infection with IGRA +/- Mantoux test to follow the testing strategy for immunocompromised (HIV infected) patients in the current NICE Tuberculosis Guidelines (1C)
– Patients who test positive for LTBI are
o assessed for any evidence of active tuberculosis disease (1C)
o treated for LTBI ac/to NICE TB guidelines, prior to transplantation (1C)
– Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
Suggestions:
Screening for Strongyloides stercoralis infection, for candidates from endemic regions, prior to transplantation (2D)
Concomitant HBV and HCV – Recommendations:
– All transplant candidates are screened for viral hepatitis. Those with HBsAg or HCV Antibody positive should test for HBV- DNA and HCV-RNA level quantitative PCR and undergo investigation for the presence of liver cirrhosis. (1C)
– All HBsAg positive patients wait listed for SOT receive treatment to ensure HBV-DNA fully suppressed (1B)
– Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication. (1C)
– Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN-III) or carcinoma in situ should receive treatment prior to transplantation. (1D)
Suggestions:
– Anti-HBc positive “alone” recipients (HBsAg and DNA negative; donor negative) do not require routine antiviral prophylaxis against HBV reactivation. (2D)
– But Anti-HBV prophylaxis may be considered for those received T-cell depleting agents (ATG). (2D)
PRE-TRANSPLANT IMMUNISATION
Recommendations:
As part of the work-up for solid organ transplantation we recommend that:
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 m IU/mL). (1B)
• Hepatitis A virus (HAV) vaccine is administered to all non-immune patients. (1D)
• Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients. (1B)
• Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL. (1C)
Suggestion:
• Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
• Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D)
• Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
We recommend that influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
CONSIDERATION OF DRUG-DRUG INTERACTIONS
Recommendations
– Full review of current medication as part of the assessment for SOT, to be repeated at least twice a year, and at every key therapeutic decision point (Not graded)
– Continuation of ART in the perioperative period following transplantation (1D)
Suggestions:
– A dose-finding trial of CNI, prior to SOT in order to determine optimum dose post-transplant. (2D)
– Pre-emptive switching away from boosted protease-inhibitors (PI)-based ART regimen, to alternative regimen, in order to minimise drug interactions (2D)
– All clinical correspondence to carry a reference to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION
Recommendations
– HIV-positive patients for kidney transplant to be offered induction therapy at the time of transplantation. (1C)
– Interleukin-2 receptor antagonist (IL-2RA) is preferable induction agent for HIV-positive recipients. (1B)
– Triple drug maintenance IS (same as non-HIV patients), including a CNI, an anti-proliferative agent and steroid, to be started at the time of kidney transplantation (1C)
Suggestion: Acute rejection is treated in HIV-positive kidney transplant recipients, in the same way as HIV-negative kidney transplant recipients (2D)
POST-TRANSPLANT PROPHYLAXIS
Recommendations:
– HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
– Toxoplasma IgG seropositive recipients with a CD4 + T-cell count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
– Minimum of 3 months CMV-prophylaxis indicated in CMV (D+/R-): seronegative recipients of organs from CMV seropositive donors (1A)
– CMV seropositive recipients can receive either 3months-prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for 3 months (1A)
Transplant patients not assessed nor treated for TB pre-transplant, should be assessed for LTBI and active TB, as recommended for patients prior to transplantation (1C)
Transplant patients who are well and were assessed and fully treated for LTBI or disease before transplantation, do not need reassessment for LTBI unless symptomatic or new exposure to tuberculosis (1C)
Post-transplant exposed to tuberculosis should be assessed as recommended in current NICE TB guidance on tuberculosis of contact tracing (1C)
With reliable prior history of treated TB infection, there is no need for further testing beyond symptom review and chest X-ray; these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
Suggestion:
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4 + count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months. (2D)
MONITORING ALLOGRAFT FUNCTION
Recommendations
– Guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
Suggestion: local practice for monitoring of the pancreas allograft is followed (Not graded)
MONITORING OF HIV VIROLOGICAL CONTROL
Recommendations
– Quantitative HIV RNA and CD4+ T-cell counts are measured regularly post Tx – at 1 month, then 2-3 monthly x1 year; and 3-6 monthly thereafter (1B)
– Persistent HIV viraemia needs drug-resistance testing to determine alternate treatment options (1D)
Suggestion: frequent monitoring of CD4 count in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR
Recommendations
– HIV-infected patients can have the same access to living donor kidney transplantation as non-infected patients (1B)
– HIV-infected people are unsuitable to be living kidney donors (1D)
Suggestion:
– Potential donors for HIV-positive recipients are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Recommendations:
Transplant of organs from HIV-infected individuals be restricted to deceased donors with:
– HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
– Information about the donor virus genotype (where possible) and current viral load
– No history of virological failure of treatment or drug resistance (1D)
· Recipients are to be informed, counselled and they have to give informed consent both at the time of listing and at the time of transplantation (1D)
Suggestion: that HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
· It is recommended that HIV-infected people are unsuitable to be living kidney donors (1D)
Indications for kidney transplantation
According to the BTS giudline no contraindication for transplant for HIV positive recepeint .
These patient need to be on HAARt treatment with cd4 count of more than 200 and undetectable HIV RNA .
HIV-positive patients are wait-listed only if–
They are concordant with treatment, particularly cART therapy
CD4+ T cell counts are >100 cells/µL.
General assessment ;
these people need to ahve genarl assessment like Screening for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii
Test for latent Mycobacterium tuberculosis infection with IGRA
Treat TB as per NICE guidance
Hepatitis B surface antigen or hepatitis C antibody positive should be investigated for the presence of liver cirrhosis
Rule out cervical and/or anal neoplasia..
THese patient suppose to haver the prober HAART therapy and better to avoid PI regiem as it may lead to HIV resistance and drug -drug interaction .
Pre transplant we need to have an idea about the status of HIV resistance if any .
Cnotranindication for transplantation;
Positive CDC crossmatch
Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer ,Pregnancy.
Multi-drug resistant HIV infection that cannot be controlled with currently available ART
INDUCTION AND IS
better to induce induction through BASILIXMIAB AND AVOID ATG.
try to use the IS and regular monitor for the interaction between HAART therapy and CNI.as it will affect the level under the curve irrespect to the trough level ,and this is could be the cause of rejection .
Still we go for HIV + donor for HIV +recipent :
the donor with good general health and imnmunity and CD4 of more than 200
Information about the donor virus such as historical genotype patterns where possible and current viral load
No history of virological failure or drug resistance
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation
Patients with HIV-infection are unsuitable to be living kidney donors
INTRODUCTION:
Scope and aim of the guidelines:
As the introduction of highly active antiretroviral therapy (HAART) in 1996, mortality in patients with human immunodeficiency virus (HIV) infection has decreased.
HIV patients are at risk of the development of chronic kidney disease and, end-stage kidney disease (ESRD) and dialysis substantially increase the risk of death and cardiovascular events in both the general and HIV-infected populations.
The aim is to provide a comprehensive summary of all aspects of assessment, selection and management of the HIV-positive transplant candidate.
Grading of recommendation:
For each recommendation the quality of evidence has been graded as: A (high) B (moderate) C (low) D (very low) For each recommendation, the strength of recommendation has been indicated as one of: Level 1 (we recommend) Level 2 (we suggest) Not graded (where there is not enough evidence to allow formal grading)
Indications for Kidney transplantation:
Recommendations:
HIV positive patients is not contraindicated for kidney transplantation if :
1) They are concordant with treatment,(1D)
2) CD4+ T cell counts are >100 cells/µL and have been
stable during the previous 3 months (1B)
3) No HIV RNA during the previous 6 months (1B)
4) No infections during the previous 6 months (1B)
5) No history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma (1B)
suggestion:
The most appropriate anti-retroviral therapy is determined before transplantation to anticipate potential drug interactions and dosing (not graded)
Indications for Pancreas Transplantation:
Recommendation:
HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation , and also in solitary pancreas or islet transplantation (Not graded)
Suggestion:
Diabetic patients with renal failure and controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Contraindications to transplantation:
Recommendations:
Absolute contraindications to kidney transplantation in patients with HIV are: Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D), Pregnancy (1D) and uncontrolled HIV infection during the last 6 months(1C).
Suggestions:
Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection.
General assessment:
Recommendations:
Follow existing guidelines for HIV transplant recipients (not graded)
HIV-specific assessment:
Recommendations:
All transplant candidates undergo careful immuno-virological and antiretroviral status review(1D),serlogy for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D), latent Mycobacterium tuberculosis infection(1C),and screened for viral hepatitis B and C (1C).
hepatitis B surface antigen positive recipients receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
patients with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D).
Not recommended:
Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) ,active HCV replication (1C), and a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1D)
Suggestions:
Solid organ transplantation may be appropriate for patients with suppressed HIV RNA, CD4 cell count below 200 cells/µL, nephrotoxic potential, significant drug-drug interactions with calcineurin inhibitors, and Strongyloides stercoralis infection.
Pancreas-specific assessment:
Recommendations:
Transplant candidates are counselled for the little experience of pancreas transplantation performed in HIV-infected patients (Not graded)
Suggestions:
Pancreas transplantation assessment includes diabetic assessment, vascular assessment, and cardiac assessment (2C).
Pre-transplant immunization:
Recommendations:
HBV (1B),HAV(1D), PPV-23(1B), VZV (1C), and influenza(1B) vaccines are administrated to non-immune patients with CD4 cell counts >200 cells/µL.
Suggestions:
DPT (2D), MMR(2D), and HPV (2C) vaccines are administrated to all patients
Consideration of drug-drug interactions:
Recommendations:
Continuation of antiretroviral therapy post transplantation (1D)
Suggestions:
Continuation of antiretroviral therapy in the perioperative period following transplantation (not graded), dose-finding trial of calcineurin inhibitors prior to transplantation(2D), pre-emptive switching away from PI regimens(2D), and referral to Liverpool HIV Drug Interactions Resource (not graded).
Induction and maintenance immunosuppression:
Recommendations:
Induction therapy is with IL-2RA (1B), followed by triple therapy maintenance immunosuppression (steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent. (1C)
Suggestions:
Acute rejection in HIV-positive and HIV-negative kidney transplant recipients treated as the same (2D)
Post-transplant prophylaxis:
Recommendations:
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia(1D), cytomegalovirus (1A), and Mycobacterium tuberculosis (1C), as recommended for patients prior to transplantation.
Suggestions:
Toxoplasma IgG seropositive recipients with a CD4+ count<200 cells/µL receive lifelong prophylaxis (2C)
Monitoring allograft function:
Recommendations:
Follow existing guidelines for post-operative care of kidney transplant recipients with HIV disease (Not graded)
Suggestions:
Follow local practice for monitoring of the pancreas allograft (Not graded)
Monitoring of HIV virological control:
Recommendations:
Quantitative HIV RNA and CD4+ T-cell counts are measured, followed by drug-resistance testing to determine treatment options.
Suggestions:
Monitoring of CD4 count in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living versus deceased donor:
Recommendations:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients(1B)
Suggestions:
Disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality:
Recommendations:
Transplant teams must be satisfied that donor consent is adequate, and procedures are transparent and established. (not graded)
Suggestions:
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate,
Use of HIV-infected donors for HIV-infected recipients:
Recommendations:
Transplantation using organs from deceased donors with HIV-infected individuals is restricted to those with HIV viral load <50 copies/mL and CD4 count >200/µL prior to brain injury.
Recipients are counseled and informed before transplantation, and HIV infection is unsuitable for living kidney donors.
Suggestions:
HIV+ organ use is restricted to those centers that have experience in transplanting HIV+ patients (Not graded)
BACKGROUND:
The use of combination antiretroviral therapy (cART) has led to a dramatic reduction in opportunistic infections and death.
22% of patients in the UK remain unaware of their HIV diagnosis, and approximately half of those newly diagnosed with HIV infection present late
Immunodeficiency is an important risk factor for chronic kidney disease (CKD) and end-stage kidney disease (ESRD) , and for liver disease progression in HCV-co-infected patients.
End-stage kidney disease and kidney transplantation in HIV positive patients:
HIV-associated nephropathy is the most severe form of CKD and the most common cause of ESRD in HIV-positive patients in the UK. Kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise eligible., with 1% of black HIV-positive and 0.1% of other ethnicities requiring renal replacement therapy.
Diabetes mellitus and pancreas transplantation:
Increased risk of diabetes mellitus itself is not associated with HIV infection.
The use of cART is associated both with the metabolic syndrome and with diabetes mellitus.
Simultaneous pancreas and kidney transplantation (SPK) has been performed in a small number of HIV-positive patients with poor outcome.
INDICATIONS FOR KIDNEY TRANSPLANTATION:
Recommendations:
Transplant indicated if HIV patients has:
Concordant with treatment, have CD4+ T cell counts >100 cells/µL, have undetectable HIV RNA, and have no history of progressive multifocal leukoencephalopathy.
Rationale:
Kidney transplant patients should be screened for HIV infection to identify who need special care.
Data shows that patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation,
Some studies show higher acute rejection rates.
INDICATIONS FOR PANCREAS TRANSPLANTATION:
Recommendations:
Diabetic patients with severe hypoglycemia considered for simultaneous kidney and pancreas transplantation if HIV and kidney function.is stable.
Rationale:
HIV-positive patients with diabetes mellitus undergoing kidney and pancreas transplantation should be counselling for higher risk procedure and its complications.
Contraindication for pancreas transplantation:
Recommendations:
Absolute contraindications include uncontrolled HIV infection, habitual and irremediable non-concordance, multi-drug resistant HIV infection, serious ongoing or recurring infection, active malignancy, and pregnancy.
Suggestions:
Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection.
Rationale:
The general criteria applicable to non-HIV kidney transplant waiting lists also apply with some criteria specific to patients with HIV.
The complement-dependent cytotoxicity (CDC) test detects complement-fixing IgG and IgM antibodies and is positive when there are high levels of circulating antibodies specific for mismatched donor HLA antigens present at the time of transplantation.
The flow cytometric crossmatch (FCXM) detects lower levels of anti-HLA antibodies and is not associated with an increased risk of hyperacute rejection but does predict early acute rejection and premature graft failure.
Infectious complications following solid-organ transplantation are common and may be life or graft-threatening.
Solid organ transplant recipients are at high risk of occurrence of cancer including human papilloma virus-associated cervical and anal carcinoma.
Cardiovascular disease is the main cause of mortality after transplantation.
Recipients with a body mass index over 35 kg/m2 are at increased risk of complications after kidney transplantation.
GENERAL ASSESSMENT:
Recommendation:
Existing guidelines regarding evaluation, selection, and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded)
Rationale
HIV-infected and non-HIV-infected kidney and pancreas transplant candidates should be assisted as the same in pre-transplant period.
HIV-SPECIFIC ASSESSMENT:
Recommendations:
All transplant candidates undergo careful immuno-virological and antiretroviral status review(D).
Serologic testing for CD4 cell count, HIV RNA level, HLA-B5701 status, nephrotoxic potential, and latent Mycobacterium tuberculosis infection.
SOT must be avoided in patients with liver cirrhosis, cervical and/or anal neoplasia, extra-cutaneous Kaposi sarcoma, Castleman’s disease, HHV8-related primary effusion lymphoma or EBV-related lymphoma.
Rationale:
Patients must be assessed pre-transplant so as to decrease infectious complications and formulate a management plan that allows safe co-administration of combination antiretroviral therapy and immunosuppression.
SOT may be done for patients with markedly suppressed HIV RNA and an absolute CD4 cell count below 200 cells/µL
Screening for latent infections:
Its important to screen for may viruses in pre-transplant period to avoid its complications and for immunization.
Viral hepatitis:
The prevalence of hepatitis B (HBV) and hepatitis C (HCV) is increased in HIV-positive patients. HIV-positive patients with replicating HBV co-infection who are listed for kidney and/or pancreas transplantation should be treated with nucleoside or nucleotide analogues to render them aviraemic prior to and after transplantation.
Malignancy:
HPV-associated cancer rates is increased in both HIV-positive patients and kidney transplant recipients, so annual screening must done by cervical smear and colonoscopy to exclude intra-epithelial neoplasia.
Pancreas specific assessment:
Recommendations:
HIV-infected patients who undergo pancreas transplantation assessment should be done in a center that regularly performs renal transplantation (1C.).
Rationale:
Patients who undergo for pancreas transplantation should be assessed for hypoglycemic unawareness, peripheral neuropathy, and autonomic neuropathy.
Pre-transplant immunization:
Recommendations:
All non-immune patients with CD4 cell counts >200 cells/µL. must be vaccinated.
Suggestions:
All patients must have diphtheria, tetanus, and pertussis (DTP) vaccine, non-immune patients must have measles, mumps, and rubella (MMR) vaccine and who at risk must have HPV vaccine.
Influenza vaccine must be given annually to patients awaiting for solid organ transplantation (1B)
Rationale:
Hepatitis B virus (HBV):
HIV-positive patients are at increased risk of chronic HBV infection, with an increased risk of cirrhosis and liver cancer.
Hepatitis A virus (HAV):
HAV vaccine is safe and well tolerated in HIV-infected patients and those with end-stage kidney disease.
Pneumococcus:
Pneumococcal vaccination must be given to HIV-positive patients with CD4 cell counts >200 cells/µL and <200 cells/ µL if there is risk factor. Repeated every 3-5 years.
Varicella-Zoster virus (VZV):
VZV vaccination recommended for asymptomatic, VZV IgG seronegative HIV positive adults with a CD4 cell count >400 cells/µL.
Diphtheria, Tetanus and Pertussis (DTP):
DTP vaccine is safe for HIV-positive patients.
Measles, mumps, and rubella (MMR):
MMR vaccine must be given to HIV+ve patients if they are measles IgG seronegative and asymptomatic with a CD4 count >200 cells/µL
Human papilloma virus (HPV):
HIV-positive patients and solid organ transplant recipients with anogenital HPV infection are at substantially increased risk of developing cervical and anogenital cancers.
Vaccination of HIV-positive young adults may reduce the risk of cervical and anogenital cancer.
Influenza:
All HIV-positive patients, especially those with serious medical conditions must have influenza vaccine.
CONSIDERATION OF DRUG-DRUG INTERACTIONS:
Recommendations:
Medication review, dose-finding trial, pre-emptive switching, the continuation of antiretroviral therapy, and referral to Liverpool HIV Drug Interactions Resource.
Rationale:
Drug reconciliation is essential to ensure accurate and up-to-date documentation of all prescribed medicines at the time of transplantation and predict potential interactions between them and immunosuppressants.
A dose-finding trial of CNI immunosuppression with therapeutic drug monitoring is recommended to optimize CNI concentrations following transplantation.
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION:
Recommendations:
HIV-positive patients eligible for kidney transplantation are offered induction therapy (triple) at the time of transplantation (1C)
HIV-positive kidney transplant recipients with acute rejection treated as same as HIV-negative kidney transplant recipients (2D).
Rationale:
The HIV-TR Investigators’ study found that conventional immunosuppression is a risk for HIV-positive kidney transplant recipients.
Induction agents:
IL-2 receptor antagonists (IL-2RA) is superior to placebo in HIV negative kidney transplantation.
lymphocyte-depleting agents are associated with lower rejection rates and reduced graft loss.
Maintenance immunosuppression:
The maintenance regimens for non-HIV kidney transplant recipients are: tacrolimus, mycophenolate, and prednisolone.
Management of acute rejection:
Corticosteroids and augmented background immunosuppression, with or without lymphocyte-depleting agents is the main treatment of acute T-cell mediated rejection.
POST-TRANSPLANT PROPHYLAXIS:
Recommendations:
HIV-positive transplant recipients must receive lifelong prophylaxis against pneumocystis pneumonia, toxoplasma IgG seropositive recipients with CD4+ count <200 cells/µL, cytomegalovirus, CMV seronegative recipients, and MAC
Rationale:
HIV-positive transplant recipients are at increase risk of opportunistic infections so they need stringent prophylactic regimens.
Pneumocystis pneumonia (PCP):
Non-HIV-infected solid organ transplant recipients may need PCP prophylaxis for at least 3-6 months post-transplant.
Toxoplasma gondii:
Co-cotrimoxazole is the most effective prophylaxis against toxoplasmosis in HIV-positive patients, but dapsone and pyrimethamine are also effective.
Cytomegalovirus:
Prevented by antiviral prophylaxis and pre-emptive therapy.
Mycobacterium tuberculosis (TB):
According to NICE guidelines transplanted patient must be assessed for latent and TB infection.
Non-tuberculosis mycobacteria (NTM):
Prophylaxis with azithromycin 1250 mg once weekly, clarithromycin 500 mg twice daily or rifabutin 300 mg once daily is indicated when CD4+ T cell count is <50/µL for 6 months.
MONITORING ALLOGRAFT FUNCTION:
Recommendations:
Follow local practice (not graded).
Rationale:
Post-operative care should be the same for HIV-infected and non-infected kidney and pancreas transplant candidates.
MONITORING OF HIV VIROLOGICAL CONTROL:
Recommendations:
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months thereafter (1B)
Patients who have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D).
Rationale:
Anti-viral treatment that is insufficient to completely suppress viral replication imposes a selective pressure that may result in the emergence of drug-resistant viral escape mutants. HIV drug resistance testing is thus part of the standard management of patients in whom viral replication is not suppressed.
CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR:
Recommendations:
Patients with HIV infection should have the same access to living donor kidney transplantation as non-infected patients.
Rationale:
Living kidney donation yields superior outcomes relative to deceased donor transplantation.
HIV-infected patients may encounter unique barriers to living donor kidney transplantation.
It is important to work collaboratively with potential donors and recipients to ensure an informed risk-benefit assessment and there may be a need to tailor pre-transplantation.
CONSENT AND CONFIDENTIALITY:
Recommendations:
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded).
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded).
Rationale:
Existing guidelines:
Good ethical practice consistently underpins clinical practice to achieve optimum outcomes.
No longer an ‘experimental’ procedure:
The risks and benefits of transplantation for HIV patients should be discussed in the same way as those for other co-morbidities.
Particular issues relating to the disclosure of a diagnosis of HIV in living donation:
Living kidney donation may involve conflict between donor consent and recipient confidentiality, so it is important to have consent from the recipient to openly discuss medical conditions.
Transplant teams should ask potential donors if there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV.
Confidence of the transplant team in the consent process while respecting recipient and donor confidentiality:
Transplant teams agree that donor consent is adequate and that procedures for ensuring this is transparent and established, but not at the expense of confidentiality.
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS:
Recommendations:
HIV+ve patients is restricted to organs from deceased donors with HIV viral load <50 copies/ML and CD4 count >200/µL for at least 6 months prior to brain injury.
HIV+ve patients are unsuitable to be living kidney donor(1D).
Rationale:
HIV-infection is regarded as an absolute medical contra-indication to organ donation by many transplant centers. However, advances in care for patients with HIV, increasing waiting times, and reports of organ donation from HIV-infected (but treatment-naïve or receiving only first line ART) individuals in South Africa showing favorable outcomes at 3 to 5 years, suggest that this approach should be reconsidered.
INTRODUCTION
Scope and aim of the guidelinesThe introduction of highly active antiretroviral therapy (HAART) in 1996 has decreased mortality in patients with HIV, but morbidity from other chronic conditions such as kidney, liver, and heart disease has increased.
HIV-infected patients are at particular risk of the development of chronic kidney disease and end-stage kidney disease (ESRD) and dialysis, which increase the risk of death and cardiovascular events.
These guidelines reflect the growing evidence base from published data on the several hundred carefully selected patients with HIV infection who have already received kidney and pancreas transplants.
Indications for Kidney transplantation
Recommendations:
HIV is not a contraindication for kidney transplantation, but HIV-positive patients must be concordant with treatment and have stable CD4+ T cell counts, undetectable HIV RNA, and no opportunistic infections.
Suggestions:
The most appropriate anti-retroviral therapy is determined before transplantation to anticipate potential drug interactions and dosing.
Indications for Pancreas Transplantation
Recommendations:
HIV-positive pancreas transplant recipients are assessed by a center with experience in kidney and islet transplantation.
Suggestions:
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have stable HIV and kidney function.
Contraindications to transplantation
Recommendations:
Contraindications to kidney transplantation in patients with HIV include uncontrolled HIV infection, habitual and irremediable non-concordance, multi-drug resistant HIV infection, serious ongoing or recurring infection, active malignancy, metastatic cancer, and pregnancy.
Suggestions:
Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection.
General assessment
Recommendations:
Existing guidelines are followed for HIV transplant recipients.
HIV-specific assessment
Recommendations:
All transplant candidates undergo immuno-virological and antiretroviral status review, serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human T-cell leukemia virus, and Toxoplasma gondii, and latent Mycobacterium tuberculosis infection.
Hepatitis B surface antigen or hepatitis C antibody positive should be quantified and investigated for liver cirrhosis.
Not recommended:
Kidney and/or pancreas transplantation in patients with liver cirrhosis, HCV replication, Castleman’s disease, HHV8, and EBV.
Suggestions:
Solid organ transplantation may be appropriate for patients with suppressed HIV RNA, CD4 cell count below 200 cells/µL, nephrotoxic potential, significant drug-drug interactions with calcineurin inhibitors, and Strongyloides stercoralis infection.
Pancreas-specific assessment
Recommendations:
Transplant candidates are carefully counseled and informed of the limited experience of pancreas transplantation in HIV-infected patients.
Suggestions:
Pancreas transplantation assessment includes diabetic assessment, vascular assessment, and cardiac assessment.
Pre-transplant immunisation
Recommendations:
HBV, HAV, PPV-23, VZV, and influenza vaccines are administered to non-immune patients with CD4 cell counts >200 cells/µL.
Suggestions:
Diphtheria, tetanus, and pertussis (DTP) vaccine are administered to all patients, measles, mumps, and rubella (MMR) to non-immune patients, and the HPV vaccine to those at risk.
Consideration of drug-drug interactions
We recommend:
Continuation of antiretroviral therapy in the post-transplant period.
We suggest:
Continuation of antiretroviral therapy in the perioperative period following transplantation, dose-finding trial of calcineurin inhibitors prior to transplantation, pre-emptive switching away from PI regimens, and referral to Liverpool HIV Drug Interactions Resource.
Induction and maintenance of immunosuppression
Recommendations:
Induction therapy is with IL-2RA, followed by triple therapy maintenance immunosuppression.
Suggestions:
Acute rejection in HIV-positive kidney transplant recipients is treated the same as in HIV-negative recipients.
Post-transplant prophylaxis
Recommendations:
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia, cytomegalovirus, and Mycobacterium tuberculosis, as recommended for patients prior to transplantation.
Suggestions:
Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL receive lifelong prophylaxis, while those with a prior history of TB infection do not require it unless TB re-exposure is suspected.
Monitoring allograft function
Recommendations:
Post-operative care for HIV-positive kidney transplant recipients is followed.
Pancreas allograft monitoring is done according to local practice.
Monitoring of HIV virological control
Recommendations:
Quantitative HIV RNA and CD4+ T-cell counts are measured, followed by drug-resistance testing to determine treatment options.
Suggestions:
Monitor CD4 count to determine the need for anti-infective prophylaxis.
Choice of living versus deceased donor
Recommendations:
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients.
Suggestions:
Disclosure of HIV status is not mandatory for potential donors.
Consent and confidentiality
Recommendations:
Transplant teams must be satisfied that donor consent is adequate and procedures are transparent and established.
Suggestions:
Living donors are asked if there are any medical conditions that could change their decision to donate, and to acknowledge that they will not be given confidential information about the recipient.
Use of HIV-infected donors for HIV-infected recipients
Recommendations:
Transplantation using organs from deceased donors with HIV-infected individuals is restricted to those with HIV viral load <50 copies/mL and CD4 count >200/µL prior to brain injury.
Recipients are counseled and informed before transplantation, and HIV infection is unsuitable for living kidney donors.
Suggestions:
HIV+ organ use is restricted to those centers that have experience in transplanting HIV+ patients (Not graded)
BACKGROUNDThe use of combination antiretroviral therapy (cART) has led to a dramatic reduction in opportunistic infections and death in the UK, but 22% of patients remain unaware of their HIV diagnosis, and half of those newly diagnosed present late are at increased risk of opportunistic infections.
End-stage kidney disease and kidney transplantation in HIV-positive patientsHIV-associated nephropathy is the most severe form of CKD and the most common cause of ESRD in HIV-positive patients in the UK. Kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise eligible., with 1% of black HIV-positive and 0.1% of other ethnicities requiring renal replacement therapy.
Diabetes mellitus and pancreas transplantationHIV infection is not associated with an increased risk of diabetes mellitus, but cART has been associated with metabolic syndrome and diabetes mellitus. SPK has been performed in a small number of HIV-positive patients, but poor outcomes have been reported.
INDICATIONS FOR KIDNEY TRANSPLANTATIONRecommendations
HIV per se is not a contraindication for kidney transplantation, but wait-listing HIV patients only if they are concordant with treatment, have CD4+ T cell counts >100 cells/µL, have undetectable HIV RNA, and have no history of progressive multifocal leukoencephalopathy.
RationaleScreening for HIV infection should be carried out on all potential kidney transplant recipients to identify those that will require specialized care.
Data on several hundred carefully selected HIV-positive patients to show that patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation, but some studies report disturbingly high acute rejection rates.
The high rejection rate may be due to difficulty in obtaining a good balance between immunosuppression and controlled viral replication, and antiretrovirals such as integrase inhibitors may simplify the use of immunosuppressants and decrease the frequency of rejection.
INDICATIONS FOR PANCREAS TRANSPLANTATIONRecommendations
Diabetic patients with severe hypoglycaemic unawareness may be considered for simultaneous kidney and pancreas transplantation if they have stable HIV and kidney function.
RationalePancreas-kidney transplants can be performed in HIV-positive patients with diabetes mellitus, but with a higher risk of procedure-related complications. Careful counseling is needed.
CONTRAINDICATIONS TO TRANSPLANTATION
Recommendations
Contraindications to kidney transplantation in patients with HIV include uncontrolled HIV infection, habitual and irremediable non-concordance, multi-drug resistant HIV infection, serious ongoing or recurring infection, active malignancy, and pregnancy.
Suggestions
Relative contraindications to kidney transplantation include positive flow cytometric crossmatch, blood-type incompatibility, treated malignancy, severe and/or uncontrolled medical problems, chronic liver disease, and HTLV infection.
Rationale
The general criteria applicable to non-HIV kidney transplant waiting lists also apply to patients with HIV.
CDC test detects complement-fixing IgG and IgM antibodies and is positive when there are high levels of circulating antibodies specific for mismatched donor HLA antigens.
FCXM detects lower levels of anti-HLA antibodies and is not associated with an increased risk of hyperacute rejection, but does predict early acute rejection and premature graft failure.
Hepatitis B or C infection may be a contraindication, but quiescent disease and a benign liver biopsy can proceed. Recipients with a body mass index over 35 kg/m2 are at increased risk of complications, such as surgical complications, a longer length of stay, increased mortality, and a higher risk of post-transplant diabetes mellitus.
GENERAL ASSESSMENTRecommendation
Existing guidelines regarding evaluation, selection, and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded)
Rationale
Pre-transplant assessment should not be different for HIV-infected and non-HIV-infected kidney and pancreas transplant candidates.
HIV-SPECIFIC ASSESSMENT
Recommendations
All transplant candidates should undergo careful immuno-virological and antiretroviral status review and serologic testing for CD4 cell count, HIV RNA level, HLA-B5701 status, nephrotoxic potential, and latent Mycobacterium tuberculosis infection.
Solid organ transplantation should be avoided in those with liver cirrhosis, cervical and/or anal neoplasia, extra-cutaneous Kaposi sarcoma, Castleman’s disease, HHV8-related primary effusion lymphoma or EBV-related lymphoma.
RationaleThe pre-transplant assessment aims to minimize infectious complications and formulate a management plan that allows safe co-administration of combination antiretroviral therapy and immunosuppression.
Solid organ transplantation may be an option for patients with fully suppressed HIV RNA and an absolute CD4 cell count below 200 cells/µL.
Screening for latent infectionsImmunization should be offered to all VZV IgG-negative patients with CD4 cell counts >200 cells/µL, and specialist advice should be sought before wait listing HTLV-1 positive transplant candidates.
LTBI should be actively sought and treated prior to solid organ transplantation, and IGRAs are more sensitive and specific than tuberculin skin tests to detect LTBI.
Viral hepatitisHIV-positive patients with replicating HBV co-infection should be treated with nucleoside or nucleotide analogs to render them aviraemic prior to and after transplantation.
Malignancy
HIV-positive patients and kidney transplant recipients should have annual cervical smears and colposcopy to exclude intraepithelial neoplasia.
PANCREAS-SPECIFIC ASSESSMENTRecommendations
Pancreas transplantation assessment in HIV-infected patients should be performed in a center that regularly performs renal transplantation and 1C.
Rationale
Patients being assessed for pancreas transplantation should be assessed for hypoglycaemic unawareness, peripheral neuropathy, and autonomic neuropathy.
PRE-TRANSPLANT IMMUNISATION
Recommendations
Vaccines are recommended for non-immune patients with CD4 cell counts >200 cells/µL.
Suggestions:Diphtheria, tetanus, and pertussis (DTP) vaccine are administered to all patients, the measles, mumps, and rubella (MMR) vaccine to non-immune patients, and the HPV vaccine to those at risk.
We recommend that the influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
Rationale
Hepatitis B virus (HBV)
HIV-positive patients are at increased risk of chronic HBV infection, with an increased risk of cirrhosis and liver cancer.
Hepatitis A virus (HAV)
HIV vaccine is safe and well tolerated in HIV-infected patients and those with end-stage kidney disease.
PneumococcusPneumococcal vaccination is recommended for HIV-positive patients with CD4 cell counts >200 cells/µL.
Varicella-Zoster virus (VZV)VZV vaccination is recommended for asymptomatic, VZV IgG seronegative HIV-positive adults with a CD4 cell count >400 cells/µL.
Diphtheria, tetanus, and pertussis (DTP)
BHIVA recommends vaccination for all HIV-positive persons in accordance with standard recommendations.
Measles, mumps, and rubella (MMR)
Two doses of MMR vaccine must be given to HIV-positive persons with seronegative and asymptomatic CD4 count >200 cells/µL.
Human papilloma virus (HPV)
HIV-positive patients and solid organ transplant recipients are at increased risk of cervical and anogenital cancers.
Vaccination of HIV-positive young adults may reduce the risk of cervical and anogenital cancer
Influenza
Vaccination is recommended for all HIV-positive patients, especially those with serious medical conditions.
CONSIDERATION OF DRUG-DRUG INTERACTIONSRecommendations
Medication review, dose-finding trial, pre-emptive switching, the continuation of antiretroviral therapy, and referral to Liverpool HIV Drug Interactions Resource.
RationaleDrug reconciliation is essential to ensure accurate and up-to-date documentation of all prescribed medicines at the time of transplantation and predict potential interactions between them and immunosuppressants.
A dose-finding trial of CNI immunosuppression with therapeutic drug monitoring is recommended to optimize CNI concentrations following transplantation.
INDUCTION AND MAINTENANCE OF IMMUNOSUPPRESSIONRecommendationsHIV-positive patients should be offered induction therapy at the time of transplantation, triple therapy, and acute rejection treated in the same way as HIV-negative recipients.
Rationale
The HIV-TR Investigators’ study found that conventional immunosuppression is a risk for HIV-positive kidney transplant recipients.
Induction agents
IL-2 receptor antagonists have been shown to be superior to placebo in HIV-negative kidney transplantation, but lymphocyte-depleting agents are associated with lower rejection rates and reduced graft loss. The evidence base for the use of lymphocyte-depleting agents in HIV-positive kidney transplantation is limited.
Maintenance immunosuppression
Tacrolimus, mycophenolate, and prednisolone are the best maintenance immunosuppressive regimens for non-HIV kidney transplant recipients.
The most effective combination in non-HIV kidney transplantation is tacrolimus, mycophenolate, and prednisolone.
Management of acute rejectionTreatment of acute T-cell mediated (cellular) rejection should be with corticosteroids and augmented background immunosuppression, with or without lymphocyte-depleting agents.
POST-TRANSPLANT PROPHYLAXIS
Recommendations
HIV-positive transplant recipients should receive lifelong prophylaxis against Pneumocystis pneumonia, Toxoplasma IgG seropositive recipients with CD4+ count <200 cells/µL, cytomegalovirus, CMV seronegative recipients, and MAC.
RationaleHIV-positive transplant recipients may require more stringent prophylactic regimens due to the increased risk of opportunistic infections.
Pneumocystis pneumonia (PCP)
Anti-Pneumocystis prophylaxis is recommended for non-HIV-infected solid organ transplant recipients for at least 3-6 months post-transplant, but longer durations may be considered.
Toxoplasma gondii
Co-cotrimoxazole is the most effective prophylaxis against toxoplasmosis in HIV-positive patients, but dapsone and pyrimethamine are also effective.
CytomegalovirusAntiviral prophylaxis and pre-emptive therapy are two major strategies for CMV prevention.
Mycobacterium tuberculosis (TB)Transplant patients should be assessed for latent TB infection or disease in accordance with NICE guidance.
Non-tuberculosis mycobacteria (NTM)
Prophylaxis against NTM is indicated when CD4+ T cell count is <50/µL for 6 months, with azithromycin 1250 mg once weekly, clarithromycin 500 mg twice daily or rifabutin 300 mg once daily.
MONITORING ALLOGRAFT FUNCTIONRecommendations
Local practices for monitoring pancreas allografts should be followed.
Rationale
Post-operative care should not be different for HIV-infected and non-infected kidney and pancreas transplant candidates. MONITORING OF HIV VIROLOGICAL CONTROLRecommendations
Monitoring HIV RNA and CD4+ T-cell counts regularly to determine need for anti-infective prophylaxis.RationaleStudies have shown that CD4+ cell counts can be affected by the type of immunosuppressive agents used, with thymoglobulin induction being associated with a greater decline in CD4+ T-cells in the first year after transplant.
Anti-viral treatment that is insufficient to completely suppress viral replication imposes selective pressure, leading to the emergence of drug-resistant viral escape mutants.
CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR
Recommendations:
Patients with HIV infection should have the same access to living donor kidney transplantation as non-infected patients, but disclosure of HIV status is not mandatory.
RationaleLiving kidney donation yields superior outcomes, but HIV-infected patients may face unique barriers.
It is important to work collaboratively with potential donors and recipients to ensure an informed risk-benefit assessment and tailor pre-transplantation education to address the unique circumstances of this patient subgroup.
CONSENT AND CONFIDENTIALITYRecommendationsThe most important details are that the standard of consent for HIV-positive transplant candidates is the same as for any other transplant, that the recipient is encouraged to disclose their diagnosis of HIV to their donor, that all living donors are made aware that there may be medical and social information about the recipient that is not disclosed, and that transplant teams must be satisfied that donor consent is adequate.
RationaleExisting guidelinesGood ethical practice is essential for successful transplantation, with BTS Ethics Committee providing support and advice.
No longer an ‘experimental’ procedureThe risks and benefits of transplantation for HIV patients should be discussed in the same way as those for other co-morbidities.
Particular issues relating to the disclosure of a diagnosis of HIV in living donationLiving kidney donation may involve conflict between donor consent and recipient confidentiality, so it is important to have consent from the recipient to openly discuss medical conditions.
Transplant teams should ask potential donors if there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV.
Confidence of the transplant team in the consent process while respecting recipient and donor confidentiality
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this is transparent and established, but not at the expense of confidentiality.
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Recommendations:
HIV+ organ use should be restricted to deceased donors with HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury.
RationaleHIV infection is not an absolute medical contra-indication to organ donation, but advances in care for patients with HIV, increasing waiting times, and reports of organ donation from HIV-infected (but treatment-naïve or receiving only first-line ART) individuals suggest it should be reconsidered.
Pre-implantation biopsies may detect donor disease, but there is a risk of organ misallocation leading to transmission of HIV to uninfected recipients.
Indications for Kidney transplantation
We recommend that:
• All potential kidney transplant recipients are screened for HIV infection (1D)
• HIV per se is not a contraindication for kidney transplantation (1B)
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that:
• The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
INDICATIONS FOR KIDNEY TRANSPLANTATION
Recommendations
We recommend that all potential kidney transplant recipients are screened for HIV infection (1D)
We recommend that HIV per se is not a contraindication for kidney transplantation (1B)
We recommend wait-listing HIV patients only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally >200 cells/µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that the most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
CONTRAINDICATIONS TO TRANSPLANTATION
Recommendations
We recommend that the following transplantation in patients with HIV:
are
absolute
contraindications
to
kidney
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <200 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
We suggest that the following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2 ) (2D)
g) HTLV infection (1D)
HIV-SPECIFIC ASSESSMENT
Recommendations
We recommend that all transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
We suggest that in selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
We recommend that patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
We suggest that antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded)
We suggest that antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D)
We recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection following the testing strategy for immunocompromised HIV infected patients in the current NICE Tuberculosis Guidelines (1C)
recommend that transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
We recommend that transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
We recommend that transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
We suggest that transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
We recommend that all transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and undergo investigation for the presence of liver cirrhosis (1C)
We recommend that all hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
We suggest that anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
We recommend that patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
PRE-TRANSPLANT IMMUNISATION
Recommendations
As part of the work-up for solid organ transplantation we recommend that:
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
• Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
• Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
• Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
We suggest that:
• Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
• Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D)
• Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
We recommend that influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
CONSIDERATION OF DRUG-DRUG INTERACTIONS
Recommendations
We suggest a full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
We suggest a dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
We suggest pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
We recommend continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
We suggest that all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION
Recommendations
We recommend that all HIV-positive patients eligible for kidney transplant offered induction therapy at the time of transplantation (1C)
We recommend that for the majority of HIV-positive patients induction thera an interleukin-2 receptor antagonist (IL-2RA) (1B)
We recommend that HIV-positive patients are given triple therapy mai immunosuppression started at the time of kidney transplantation, including a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
We suggest that acute rejection is treated in HIV-positive kidney transplant r in the same way as HIV-negative kidney transplant recipients (2D)
POST-TRANSPLANT PROPHYLAXIS
Recommendations
We recommend that HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
We suggest that Toxoplasma IgG seropositive recipients with a CD4 + count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
We recommend that prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
We recommend that CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C)
We suggest that where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
We suggest that prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4 + count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
MONITORING ALLOGRAFT FUNCTION
Recommendations
We recommend that existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
We suggest that local practice for monitoring of the pancreas allograft is followed (Not graded)
MONITORING OF HIV VIROLOGICAL CONTROL
Recommendations
We recommend that quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months thereafter (1B)
We suggest that more frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
We recommend that if patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
CHOICE OF LIVING VERSUS DECEASED KIDNEY DONOR
Recommendations
We recommend that patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
We suggest that potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
We recommend that patients with HIV infection are unsuitable to be living kidney donors (1D)
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Recommendations:
We recommend that transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
– HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
– Information about the donor virus such as historical genotype patterns where possible and current viral load
– No history of virological failure or drug resistance (1D)
We recommend that recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
We suggest that HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
We recommend that patients with HIV-infection are unsuitable to be living kidney donors (1D)
Indications for kidney transplantation
According to the BTS giudline no contraindication for transplant for HIV positive recepeint .
These patient need to be on HAARt treatment with cd4 count of more than 200 and undetectable HIV RNA .
HIV-positive patients are wait-listed only if–
They are concordant with treatment, particularly cART therapy
CD4+ T cell counts are >100 cells/µL.
General assessment ;
these people need to ahve genarl assessment like Screening for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii
Test for latent Mycobacterium tuberculosis infection with IGRA
Treat TB as per NICE guidance
Hepatitis B surface antigen or hepatitis C antibody positive should be investigated for the presence of liver cirrhosis
Rule out cervical and/or anal neoplasia..
THese patient suppose to haver the prober HAART therapy and better to avoid PI regiem as it may lead to HIV resistance and drug -drug interaction .
Pre transplant we need to have an idea about the status of HIV resistance if any .
Cnotranindication for transplantation;
Positive CDC crossmatch
Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer ,Pregnancy.
Multi-drug resistant HIV infection that cannot be controlled with currently available ART
INDUCTION AND IS
better to induce induction through BASILIXMIAB AND AVOID ATG.
try to use the IS and regular monitor for the interaction between HAART therapy and CNI.as it will affect the level under the curve irrespect to the trough level ,and this is could be the cause of rejection .
Still we go for HIV + donor for HIV +recipent :
the donor with good general health and imnmunity and CD4 of more than 200
Information about the donor virus such as historical genotype patterns where possible and current viral load
No history of virological failure or drug resistance
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation
Patients with HIV-infection are unsuitable to be living kidney donors
Kidney & Pancreas Transplantation in Patients with HIV
Indications for Kidney transplantation
Recommendations
All potential kidney transplant recipients are screened for HIV infection
HIV per se is not a contraindication for kidney transplantation
HIV-positive patients are wait-listed only if–
They are concordant with treatment, particularly cART therapy
CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months
HIV RNA has been undetectable during the previous 6 months
No opportunistic infections have occurred during the previous 6 months
No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
Suggestions
The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV sppecialist
Indications for Pancreas Transplantation
Recommendations
Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min)
Contraindications to transplantation
Uncontrolled HIV infection (CD4+ T cell levels persistently
Habitual and irremediable non-concordance
Multi-drug resistant HIV infection that cannot be controlled with currently available ART
Positive CDC crossmatch
Serious ongoing or recurring infection
Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer ,Pregnancy
General assessment
All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile
Patients with HIV RNA levels >200 copies /ml are suitable for SOT
Screening for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii
Test for latent Mycobacterium tuberculosis infection with IGRA
Treat TB as per NICE guidance
Hepatitis B surface antigen or hepatitis C antibody positive should be investigated for the presence of liver cirrhosis
Rule out cervical and/or anal neoplasia
Suggestions
SOT may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL
Avoid nephrotoxic antivirals
Avoid ritonavir and cobicista as drug interaction with CNI
Scrren for Strongyloides stercoralis
Pre-transplant immunisation
Hepatitis B virus (HBV) vaccine
Influenza vaccine
Diphtheria, tetanus and pertussis (DTP) vaccine
Measles, mumps and rubella
Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition
Induction and maintenance immunosuppression
HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) and triple therapy maintenance immunosuppression including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent
Post-transplant prophylaxis
Pneumocystis pneumonia
Prophylaxis against cytomegalovirus – 3 months
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent
Monitoring
Follow local practice
Monitoring of HIV virological control
Use of HIV-infected donors for HIV-infected recipients
If-
HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
Information about the donor virus such as historical genotype patterns where possible and current viral load
No history of virological failure or drug resistance
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation
Patients with HIV-infection are unsuitable to be living kidney donors
I. Kidney & Pancreas Transplantation in Patients with HIV
Summarise this article
Indications for kidney transplantation
– screen all potential kidney transplant recipients for HIV infection
– HIV is not a contraindication for kidney transplantation
– pre-transplant requirements include: adherence to HAART, CD4 >100 (ideally >200), stable CD4 for the last 3months, undetectable viral load for the last 6months, no OIs in the last 6months, no history of PML, chronic intestinal cryptosporidiosis or lymphoma
– decide on the most appropriate HAART before transplantation bearing in mind the potential drug-drug interactions
Indications for kidney transplantation
– consider diabetes patients in ESKD with controlled HIV infection for simultaneous kidney and pancreas transplantation
– consider solitary pancreas or islet transplantation in diabetic patients with severe hypoglycemic unawareness with well controlled HIV and stable kidney function (eGFR >40)
Absolute contraindications to kidney transplantation in HIV positive patients
– uncontrolled HIV infection i.e., CD4 <100 in the last 6 months, persistently detectable viralload in the last 3 months
– major psychiatric disease, irresolvable psychosocial problems, persistent substance abuse
– multidrug resistant HIV infection which cannot be controlled with the currently available HAART
– positive CDC crossmatch
– serious ongoing or recurring infection, including documented history of PML
– active malignancy on treatment, metastatic cancer, disseminated or untreated cancer
– pregnancy
Relative contraindications to kidney transplantation in HIV positive patients
– positive flow cytometric crossmatch (FCXM)
– ABO incompatibility
– treated malignancy including extracutaneous kaposi sarcoma
– severe and/ or uncontrolled medical problems which are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy
– chronic liver disease
– BMI >35
– HTLV infection
General assessment
– for all potential HIV positive transplant recipients, follow the existing guidelines on evaluation, selection and preparation of the potential transplant recipient
HIV specific assessment
– all potential transplant recipients should undergo a thorough immune-virological and antiretroviral status review i.e., review the CD4 count, HIV RNA level (viral load), current and previous
HAART regimens, HLA-B5701 status, HIV resistance profile
– patients with HIV RNA levels <200 copies/ml , otherwise well and adherent to their medications can be considered for SOT
– screen transplant candidates for syphilis, HSV, EBV, CMV, VZV, HTLV, toxoplasma gondii
– test transplant candidates for LTBI using IGRA ± mantoux test
– rule out active TB disease in transplant candidates who test positive for LTBI
– if there is evidence for active TB disease, treat the transplant candidates as per the guidelines
– if active TB has been ruled out, treat the transplant candidate for LTBI as per the guidelines
– screen all transplant candidates for viral hepatitis i.e., HBV and HCV
– if HBsAg or HCV Ab positive, the HBV DNA and HCV RNA levels should be quantified and be investigated for in the presence of liver cirrhosis
– all HBsAg positive potential transplant recipients on the waiting list for SOT should receive treatment to ensure HBV DNA is fully suppressed
– assess for presence of cervical and/ or anal neoplasia, treat those with advanced cervical/ anal intraepithelial neoplasia (CIN/ AIN III) or carcinoma in situ (CIS) prior to SOT
– do not offer kidney and/ or pancreas transplantation in patients with liver cirrhosis and in those with evidence of active HCV replication
– do not offer SOT in patients with HHV8-related primary effusion lymphoma or EBV-related lymphoma
– in selected cases, SOT may be appropriate for patients with fully suppressed HIV RNA and a CD4 <200 but >100
– in kidney transplantation, avoid HAART with nephrotoxic potential e.g., TDF, atazanavir if suitable alternatives are available
– in SOT, avoid HAART with significant drug-drug interactions with CNIs (e.g., ritonavir, cobicistat) if suitable alternatives are available
– screen for strongyloides stercoralis prior to transplantation in transplant candidates from endemic areas
– routine antiviral prophylaxis against HBV reactivation is not required in anti-HBc positive “alone” recipients (donor negative recipient HBsAg and HBV DNA negative) but for patients with increased risk of reactivation e..g., those on lymphodepleting therapy, antiviral prophylaxis can be given
Pancreas-specific assessment this entails:
– diabetic assessment for hypoglycemia unawareness, peripheral
neuropathy, autonomic neuropathy
– vascular assessment via ultrasound for limb vessels, consider non-contrast CT of the aorta and iliacs
– extensive cardiac assessment
Pretransplant immunization
– HBV vaccine should be administered to all non-immune patients (HBsAb titres <10mIU/mL)
– HAV vaccine is administered to all non-immune patients
– PPV-23 is administered to all patients
– VZV vaccine is administered to non-immune patients with CD4 >200
– Influenza vaccine is administered annually to patients awaiting SOT
– DTP vaccine is administered to all patients
– MMR vaccine is administered to all patients who are nonimmune to measles
– HPV vaccine is offered to patients at risk of HPV acquisition
Consideration of drug-drug interactions
– continue HAART in the perioperative period post-transplantation
– review the full and current medication list bi-annually and every time a therapeutic decision is made
– carry out a dose-finding trial of CNIs prior to SOT so as to determine the optimum doses to initiate post-transplant
– minimize drug-drug interactions by pre-emptively switching from boosted PI-based HAART regimens if alternatives are available
Induction and maintenance immunosuppression
– all HIV positive potential kidney transplant recipients should be offered induction therapy during transplantation
– interleukin-2 receptor antagonist (IL-2RA) is offered as induction therapy for most HIV-positive patients
– triple therapy maintenance immunosuppression (CNI, antiproliferative agent, steroids) is started at the time of kidney transplantation in HIV-positive patients
– manage acute rejection in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients
Post-transplant prophylaxis
– in HIV-positive transplant recipients, offer life-long prophylaxis against PCP following transplantation
– offer CMV prophylaxis in CMV seronegative recipients of organs from seropositive donors for a minimum of 3 months
– CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months
– assess transplant patients who are well and were not assessed and treated for LTBI or active disease prior to transplant
– those who were assessed prior to transplantation do not need reassessment for LTBI unless there is a new history of exposure to TB
– offer lifelong toxoplasmosis prophylaxis to toxoplasma IgG seropositive recipients with a CD4 <200 and any recipient of an organ from a seropositive donor
– there is no need for further testing beyond symptom review and CXR in patients with a reliable history of treated TB infection, such patients do not require TB prophylaxis unless TB re-exposure is suspected
– offer prophylaxis against MAC when CD4 is <50, stop once CD4 is >100 for 6 months
Monitoring allograft function
– regarding post-operative care of the HIV-positive kidney transplant recipient, follow the existing guidelines
– for pancreas allograft monitoring, follow the local practice
Monitoring HIV virological control
– monitor HIV RNA levels and CD4 at 1-month post-transplant, then every 2-3 months for the 1st year then every 3-6 months thereafter
– for patients with persistent HIV viremia, drug resistance testing is done to determine the treatment options
– consider more frequent CD4 count monitoring in patients receiving depleting antibodies so as to determine the need for anti-infective prophylaxis
Choice of living versus deceased donor
– HIV-positive patients have the same access to living donor kidney transplantation as non-infected patients
– HIV-positive individuals are not suitable living kidney donors (1D)
– potential donors for HIV-positive patients should be informed about the medical, surgical and psychosocial factors that may enhance the recipient’s morbidity and mortality risk, however disclosure of the recipient’s HIV status is not mandatory (not graded)
Consent and confidentiality
– for all transplantation involving HIV-positive patients, follow the existing guidelines on the ethics of deceased and living donor transplantation
– the standard of consent for HIV-positive transplant candidates is the same as for any other transplant
– the recipient is encouraged to disclose their HIV status to their donor wherever possible (not graded)
– ask the living donor whether there are any medical conditions that would make them change their decision to donate without highlighting HIV (not graded)
– living donors should be made aware that there are medical and social information regading the donor that has not been disclosed
– living donors should acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant
Use of HIV-infected donors for HIV-infected recipients
– transplantation using HIV-positive organs is restricted to organs from deceased donors with: –
– recipients should be counseled and give informed consent both at the time of listing and during transplantation
– HIV-positive individuals are unsuitable to be living kidney donors (1D)
– restrict HIV-positive organ use to centers that have experience in transplanting HIV-positive patients
Summary:
Indications for Kidney transplantation
Recommendations are:
· All potential kidney transplant recipients are screened for HIV infection
· HIV per se is not a contraindication for kidney transplantation
· HIV-positive patients are wait-listed only if: a) They are concordant with treatment, particularly cART therapy (1D) b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months c) HIV RNA has been undetectable during the previous 6 months d) No opportunistic infections have occurred during the previous 6 months e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
· The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication
Indications for Pancreas Transplantation
Recommendations are:
· Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation
· Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation
· Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min)
Contraindications to transplantation
Recommendations are:
· The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently less than 100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART
d) Positive complement-dependent cytotoxic (CDC) crossmatch
e) Serious ongoing or recurring infection, including documented history of PML
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer g) Pregnancy
· The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM)
b) Blood-type incompatibility
c) Treated malignancy, including extracutaneous Kaposi sarcoma
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy
e) Chronic liver disease
f) Marked obesity (BMI >35 kg/m2 ) (2D) g) HTLV infection
General assessment
Recommendations are:
· Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease
HIV-specific assessment
Recommendations are:
· All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile
· Patients with HIV RNA levels 200 cells/µL
· Influenza vaccine is administered annually to patients awaiting solid organ transplantation We suggest that: • Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients • Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles • Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition
· Consideration of drug-drug interaction recommendations are:
· Continuation of antiretroviral therapy in the perioperative period following transplantation
· A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point
· A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
· Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions
· HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
· Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
INDICATIONS FOR KIDNEY TRANSPLANTATION
All potential kidney transplant recipients are screened for HIV infection (1D) We recommend that HIV per se is not a contraindication for kidney transplantation (1B) We recommend wait-listing HIV patients only if: a) They are concordant with treatment, particularly cART therapy (1D) b) Their CD4+ T cell counts are >100 cells/µL (ideally >200 cells/µL) and have been stable during the previous 3 months (1B) c) HIV RNA has been undetectable during the previous 6 months (1B) d) No opportunistic infections have occurred during the previous 6 months (1B) e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
CONTRAINDICATIONS TO TRANSPLANTATION
The following are absolute contraindications to kidney transplantation in patients with HIV: a) Uncontrolled HIV infection (CD4+ T cell levels persistently 35 kg/m2 ) (2D) g) HTLV infection (1D) b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D) c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D) d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D) e) Serious ongoing or recurring infection, including documented history of PML (1D) f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D) g) Pregnancy (1D) We suggest that the following are relative contraindications to kidney transplantation: a) Positive flow cytometric crossmatch (FCXM) (1D) b) Blood-type incompatibility (2D) c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C) d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D) e) Chronic liver disease (2D) f) Marked obesity (BMI >35 kg/m2 ) (2D) g) HTLV infection (1D)
HIV-SPECIFIC ASSESSMENT
All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D) We suggest that in selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C) We recommend that patients with HIV RNA levels less than 200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
We suggest that antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded) We suggest that antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D) We recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D) We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C) We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection following the testing strategy for immunocompromised HIV infected patients in the current NICE Tuberculosis Guidelines (1C) We recommend that transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C) We recommend that transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C) We recommend that transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C) We suggest that transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D) We recommend that all transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and undergo investigation for the presence of liver cirrhosis (1C) We recommend that all hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B) We suggest that anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D) We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C) We recommend that patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D) 40 We recommend against solid organ transplantation in patients with a history of extracutaneous Kaposi sarcoma, Castleman’s disease, human herpes virus 8 (HHV8)- related primary effusion lymphoma or Epstein-Barr virus (EBV)-related lymphoma (1D)
PRE-TRANSPLANT IMMUNISATION
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres 200 cells/µL (1C) We suggest that: • Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D) • Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D) • Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C) We recommend that influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
CONSIDERATION OF DRUG-DRUG INTERACTIONS
A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded) We suggest a dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D) We suggest pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D) We recommend continuation of antiretroviral therapy in the perioperative period following transplantation (1D) We suggest that all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
INDUCTION AND MAINTENANCE IMMUNOSUPPRESSION
All HIV-positive patients eligible for kidney transplanoffered induction therapy at the time of transplantation (1C) We recommend that for the majority of HIV-positive patients induction theraan interleukin-2 receptor antagonist (IL-2RA) (1B) We recommend that HIV-positive patients are given triple therapy maimmunosuppression started at the time of kidney transplantation, includinga calcineurin inhibitor (CNI) and an anti-proliferative agent (1C) We suggest that acute rejection is treated in HIV-positive kidney transplant in the same way as HIV-negative kidney transplant recipients (2D)
POST-TRANSPLANT PROPHYLAXIS
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D) We suggest that Toxoplasma IgG seropositive recipients with a CD4+ count less than 200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C) We recommend that prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A) We recommend that CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A) Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C) Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C) Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C) We suggest that where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D) 68 We suggest that prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
MONITORING ALLOGRAFT FUNCTION
Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded) We suggest that local practice for monitoring of the pancreas allograft is followed (Not graded)
MONITORING OF HIV VIROLOGICAL CONTROL
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year and every 3-6 months thereafter (1B) We suggest that more frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D) We recommend that if patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
CONSENT AND CONFIDENTIALITY
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded) We recommend that the standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded) We suggest that, wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded) We suggest that all living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded) We suggest that all living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded) We suggest that all living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded) We recommend that transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded)
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with: – HIV viral load 200/µL for at least 6 months prior to brain injury – Information about the donor virus such as historical genotype patterns where possible and current viral load – No history of virological failure or drug resistance (1D) We recommend that recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D) We suggest that HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded) We recommend that patients with HIV-infection are unsuitable to be living kidney donors (1D)
The article deals with the British Transplantation society guidelines for kidney & pancreas transplantation in patients with HIV, published in 2015, and revised in January 2017.
Use of combination antiretroviral therapy (cART) has changed the prognosis of human immunodeficiency virus (HIV) infected patients. HIV associated nephropathy (HIVAN) is the commonest cause of end stage renal disease (ESRD) in HIV-positive patients. Survivla rates for patients are higher if they undergo a renal transplant rather than remaining on dialysis. cART use has made it possible to offer renal transplant to HIV-positive patients, if they fulfil the criteria laid down.
Indications for kidney transplantation: All potential kidney transplant recipients (KTRs) should be screened for HIV and if positive, they can be wait-listed provided they are concordant to treatment (especially cART), have undetectable HIV RNA for last 6 months, have stable and >100 cells/microL (ideally >200) level of CD4 counts for last 3 months, without any history of opportunistic infections in last 6 months, and no history of lymphoma, cryptosporidiosis, or progressive multifocal leukoencephalopathy (PML).
The most appropriate cART for the prospective KTR can be decided in conjunction with an HIV specialist keeping in mind the interactions with immunosuppressive medications required post-transplant (using integrase inhibitors which do not inhibit CYP450), to prevent rejections post-transplant.
Indications for Pancreas transplantation: Simultaneous pancreas and kidney transplant (SPK) should be considered for HIV-infected diabetics with renal failure. Solitary pancreas or islet transplantation should be offered to HIV-infected diabetics with severe hypoglycemic unawareness (despite best possible diabetic care), and having eGFR >40ml/min. Prospective HIV-positive pancreas transplant recipients should be assessed in a centre with such experience. The HIV-infection should be well controlled before proceeding with transplant.
Contraindications to kidney transplantation in HIV-positive patients: Absolute contraindications include pregnancy, a positive CDC crossmatch (no evidence to support safety of desensitization in HIV-positive patients), uncontrolled HIV infection (persistently detectable HIV RNA for last 3 months, and CD4 T cell </microL for last 6 months), ongoing or recurring infection (empyema, Aspergillus infection, methicillin resistant staphylococcus aureus, MRSA, vancomycin-resistant enterococcus, VRE, active cytomegalovirus, CMV, active tuberculosis, influenza virus, respiratory syncytial virus, RSV, PML), active malignancy under treatment, any metastasis or untreated cancer, multi-drug resistant HIV infection, or habitual non-adherence due to psychiatric disease, psychosocial problems or substance abuse. Patients with advanced cardiopulmonary disease are also excluded. Patients with chronic hepatitis B and C virus infection need further evaluation and, in presence of active hepatitis or cirrhosis, might not be candidate for transplantation.
Relative contraindications include a positive flowcytometry crossmatch, blood group incompatibility, treated malignancy (wait-period of 2-5 years recommended according to the malignancy type), BMI >35 (increased surgical complications), HTLV infection (risk of developing leukemia and myelopathy post-transplant), chronic liver disease (CLD), or severe medical problems not likely to improve post-transplant (like elderly patient with marked obesity, extensive smoking history, marked obesity and extensive cardiac disease).
General assessment: Existing guidelines for prospective KTR evaluation, selection, and preparation should be followed in HIV-positive patients.
HIV-specific assessment: Prospective transplant recipient should be evaluated with respect to history of antiretroviral therapy, HIV viral load, CD4 count, HLA-B5701 status, and HIV resistance profile. Assessment for infections and malignancies like syphilis, HSV (Herpes simplex virus), EBV (Epstein Barr virus), CMV (cytomegalovirus), VZV (varicella zoster virus), HTLV (human T-cell leukemia virus), Toxoplasma gondii, active tuberculosis, latent Tuberculosis, HBV, HCV, cervical and/or anal neoplasia evaluation should be done. Serological HBV or HCV positivity should be further evaluated with HBV DNA/ HCV RNA levels and for presence of liver cirrhosis. Anti-HBc positive ‘alone’ recipients, if given lymphodepleting agents, should be given antiviral prophylaxis. Active tuberculosis, HBV infection, HCV infection and cervical/ anal intraepithelial neoplasia or carcinoma in situ must be treated prior to transplant.
Patients with liver cirrhosis and active HCV replication or with history of Castleman’s disease, EBV related lymphoma, or Human herpes virus-8 (HHV-8) related primary effusion lymphoma should not be transplanted.
Appropriate cART regimen should be used, avoiding nephrotoxic drugs (tenofovir and atazanavir) and drugs having interactions with CNIs (ritonavir and cobicistat). In patients with low level viremia (HIV RNA <200 copies/ml), transplant can be considered after antiretroviral resistance test.
Pancreas-specific assessment: Transplant candidates should be counselled and informed regarding paucity of experience in this field, and the transplant should be performed in a centre having experience in performing pancreas transplants as well as transplants in HIV-infected patients. Assessment should include diabetic assessment (hypoglycemic awareness, autonomic neuropathy, and peripheral neuropathy), vascular assessment (peripheral vessels, aorta and iliac vessel assessment using ultrasound and CT), and cardiac assessment (ECG, myocardial perfusion scan or dobutamine stress echocardiography, and coronary angiography – in age >50, type 1 diabetes, ESRD for > 3 years, and significant cardiac history).
Pre-transplant immunization: The patient should be immunized with HBV vaccine (larger and more frequent doses may be required), Hepatitis A virus (HAV) vaccine (2 doses if CD$ >300, and 3 doses if CD4 <300), pneumococcal vaccine (for those with CD4>200, and for those with CD4<200 if associated CLD, CKD or DM), varicella zoster virus vaccine (for those with CD4>400), annual influenza vaccine (especially with CKD, CLD or DM), human papilloma virus vaccine (for at-risk patients), measles, mumps and rubella (MMR) vaccine (for those with CD4>200), and diphtheria, tetanus and pertussis (DTP) vaccine.
Consideration of drug-drug interactions: A dose-finding trial of CNIs pre-transplant can be done to detect the optimal dose required post-transplant (to prevent rejections post-transplant due to inadequate CNI dose), especially in those on protease inhibitors. Pre-operative switching of ART from boosted protease inhibitors (which increase CNI and mTOR inhibitor drug levels) to alternative agents should be done. ART should be continued in post-transplant period. 6 monthly medication review should be done. HIV drug interaction resource should be used by physicians to find put any potential drug-interaction post-transplant. Both patients and clinicians should be aware of immunosuppressive drug timings, dosages, frequencies, concentrations, and interactions with other drugs.
Induction and maintenance immunosuppression: All patients should be offered induction therapy, with use of interleukin-2 receptor antagonist in majority of the patients. Evidence for use of lymphocyte-depleting agents and belatacept is insufficient to recommend their use. CNI, steroids, and anti-proliferative agent based triple drug maintenance immunosuppressive regime should be started at time of transplant (due to high rejection rates seen in HIV-infected patients). Treatment of acute rejection warrants the use of standard protocol (as for HIV-negative recipient).
Post-transplant prophylaxis: It would include prophylaxis against pneumocystis pneumonia (lifelong cotrimoxazole 480 mg, dapsone 100 mg daily, or aerosolized pentamidine 300 mg monthly), cytomegalovirus (minimum 3 months for CMV seronegative recipients of seropositive donor organ), toxoplasma (cotrimoxazole 960 mg daily lifelong, or dapsone 50 mg daily with pyrimethamine 50 mg weekly, in seropositive recipients with CD4 <200), and mycobacterium avium complex, MAC (with azithromycin 1250 mg weekly, clarithromycin 500 mg twice a day, or rifabutin 300 mg daily, if CD4 <50). Assessment for tuberculosis disease or latent TB infection should be done only if not done pre-transplant or in the event of re-exposure.
Post-transplant monitoring of allograft function: It should be done as per standard protocol followed for non-HIV-infected KTRs. For pancreas recipients, local practice should be followed in view of varying practices all over UK.
Monitoring of HIV virological load: Quantitative HIV RNA and CD4+ T cell count should be measured at 1 month, then every 2-3 month till 1 year, and then every 3-6 monthly. More frequent CD4 count monitoring in those receiving lymphocyte depleting agents. Drug resistance testing may be required in case of persistent viremia.
Choice of living versus deceased kidney donor: HIV-infected patients should have same access to living donor transplantation as that of HIV-noninfected patients. HIV-infected patients are not suitable for living kidney donation due to increased risk of kidney disease in them. The medical, surgical, and psychosocial factors of the recipient should be informed to the donor, but the disclosure of recipient HIV status is not mandatory.
Consent and confidentiality: Existing guidelines on ethics and standard consent protocol should be followed in all patients. The recipient is encouraged to disclose their HIV status to the prospective donor. All living donor should be aware and acknowledge that complete medical and social information of the recipient which is not relevant to the kidney transplant outcome might not be provided to them and should be asked if presence of any medical condition in the recipient would lead to change in their decision to donate.
Use of HIV-infected donors for HIV-infected recipients: Deceased donors with HIV ciral load <50 copies/ml and CD4 count >200 for minimum 6 months prior to brain injury, with no history of virological failure or drug resistance can be transplanted to HIV-positive recipients after counselling (regarding risk of transmission of drug resistance and opportunistic infections, as well as risk of HIV-associated nephropathy in the donor organ) and written informed consent. HIV/HCV con-infected donor organ should not be used. HIV positive organ use for transplantation should be done only in centres experienced in transplanting HV-positive patients. HIV-infected patients are not suitable for living kidney donation due to increased risk of kidney disease in them.
I. Kidney & Pancreas Transplantation in Patients with HIV
Indications for Kidney transplantation
· All potential kidney transplant recipients are screened for HIV infection (1D)
· HIV per se is not a contraindication for kidney transplantation (1B)
· HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
· The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist.
Indications for Pancreas Transplantation
· Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation
· Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
· Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min)
Contraindications to transplantation
· The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during
the last 6 months and HIV RNA persistently detectable during the last 3 months)
(1C)
b) Habitual and irremediable non-concordance ( mostly due to severe psychiatric illness) (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available
ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, (history of PML) (1D)
f) Active malignancy, metastasis, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
· The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2 ) (2D)
g) HTLV infection (1D)
General assessment
· Existing guidelines regarding evaluation, selection and preparation of the candidates are followed for all candidates with HIV disease
HIV-specific assessment
· All transplant candidates undergo careful immuno-virological and antiretroviral status review. (1D)
· Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
· Transplant candidates undergo serologic testing for syphilis, HSV, EBV, CMV, VZV, human T-cell leukemia, and Toxoplasma gondii (1D)
· Transplant candidates are tested for LTBI with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
· Transplant candidates who test positive for LTBI are assessed for any evidence of active tuberculosis disease (1C)
· Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
· Transplant candidates with LTBI, in whom active disease has been excluded are treated for LTBI, according to current NICE TB guidelines, prior to transplantation (1C)
· All transplant candidates are screened for viral hepatitis. Those found to be HBsAg or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
· All HBsAg (+) patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
· Patients considered for SOT are assessed for the presence of cervical and/or anal neoplasia; those with advanced stage be treated before transplantation (1D)
· Kidney and/or pancreas transplantation is not recommended in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
· SOT is not recommended in patients with a history of Castleman’s disease, (HHV8)-related primary effusion lymphoma or (EBV)- related lymphoma (1D)
· In selected cases, SOT may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
· Nephrotoxic Antiretrovirals (tenofovir, atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available.
· Antiretrovirals with significant drug-drug interactions with CNI (ritonavir and cobicistat) are avoided in the setting of SOT if suitable alternatives are available (2D)
· Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
· Anti-HBc positive “alone” recipients do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (2D)
Pancreas-specific assessment
· Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C)
· Transplant candidates are carefully counseled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients.
· Pancreas transplantation assessment in patients with HIV includes:
a) Diabetic assessment b) Vascular assessment c) Extensive cardiac assessment (2C)
Pre-transplant immunization
· HBV vaccine is administered to all non-immune patients (HBs antibody titers <10 mIU/mL) (1B) • Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D) • Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B) • Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
· Influenza vaccine is administered annually to patients awaiting SOT (1B)
· Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
· MMR vaccine is administered to all patients who are nonimmune to measles (2D)
· Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
Consideration of drug-drug interactions
· Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
· A full and current medication review as part of the assessment for SOT, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point.
· A dose-finding trial of CNIs prior to SOT in order to determine optimum doses to initiate post-transplant (2D)
· Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
· That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (http://www.hiv-druginteractions.org)
Induction and maintenance immunosuppression
· All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
· For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
· HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a CNI, and an anti-proliferative agent (1C)
· Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
· HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
· Prophylaxis against CMV is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
· CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
· Transplant patients who are well and were not assessed and treated for LTBI or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
· Transplant patients who are well and were assessed and treated for LTBI or disease before transplantation do not need re-assessment for LTBI unless there is a new history of exposure to TB (1C)
· Transplant patients who are re-exposed to TB after transplantation should be assessed for LTBI and/or disease as recommended in current NICE TB guidance on TB contact tracing (1C)
· Toxoplasma IgG (+) recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor (+) for toxoplasmosis receive lifelong prophylaxis (2C)
· Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
· Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
Monitoring allograft function
· Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease.
· Local practice for monitoring of the pancreas allograft is followed.
Monitoring of HIV virological control
· Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
· If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
· More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living versus deceased donor
· Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
· Patients with HIV infection are unsuitable to be living kidney donors (1D)
· Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory.
Consent and confidentiality
· Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease.
· The standard of consent for HIV-positive transplant candidates is the same as for any other transplant.
· Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance.
· Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor
· All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV
· All living donors are made aware that there may be medical and social information about the recipient that is not disclosed.
· All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant
Use of HIV-infected donors for HIV-infected recipients
· Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
b) Information about the donor virus (genotype and current viral load)
c) No history of virological failure or drug resistance (1D)
· Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
· Patients with HIV-infection are unsuitable to be living kidney donors (1D)
· HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients
Summary
Prerequisite for Kidney transplantation
• All recipient should be screened for HIV infection (1D)
• HIV-positive patients can be kept in wait-listed only if:
a) On cART therapy (1D)
b) CD4+ T cell counts >100 cells/µL (ideally > 200 cells/ µL) for 3 months (1B)
c) HIV RNA undetectable during the previous 6 months (1B)
d) No opportunistic infections during the previous 6 months (1B)
e) No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Indications for Pancreas Transplantation
• Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
• Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded)
Contraindications to transplantation
a) Standard contraindication of renal transplant
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
g) Pregnancy (1D)
Relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2 ) (2D)
g) HTLV infection (1D)
Vaccination
Need to take following vaccination.
• Influenza vaccine (1B)
• Diphtheria, tetanus and pertussis (DTP) (2D)
• Measles, mumps and rubella (MMR) (2D)
• Human papilloma virus (HPV)(2C)
Drugs
Monitor drug-drug interactions.
• A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
• Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens,in order to minimise drug interactions (2D)
Induction Therapy
• Are offered induction therapy at the time of transplantation (1C)
• For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• Maintenance immunosuppression with triple therapy started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
• Acute rejection is treated in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
• Need lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
• Cytomegalovirus prophylaxis for a minimum of 3 months (1A)
• CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
• Need mycobacterium tuberculosis latent infection or disease treatment before transplantation (1C)
•Prophylaxis for Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
• Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL(2D)
Monitoring allograft function
• Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
• If HIV viraemia persistent, drug-resistance testing is carried out (1D)
• More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies (2D)
Choice of living versus deceased donor
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D)
• Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality
• Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
• All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
• HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
SPK IN HIV RECIPIENT
HIV is not a contraindication for transplantation
indication of KT
All potential kidney transplant recipients are screened for HIV infection (1D)
• HIV per se is not a contraindication for kidney transplantation (1B)
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been
stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma
CONTRAINDICATION TO KT
Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during
the last 6 months and HIV RNA persistently detectable during the last 3 months)
(1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric
disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available
ART (1D)
SCREENING
Transplant candidates undergo serologic testing for syphilis, herpes simplex virus,
Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus
and Toxoplasma gondii
LTBI
KT not advised in case of liver cirrhosis and lymphoma associated with HHSV8 and EBV
Pancrea transplant should be done in centre regular with HIV recioients and also pancreas transplant BOTH
IMMUNIZATION
HBVB HAV , VZV, PNEIUMOCOCCAL, INFLUENZA, vaccins shold be given
INDUCTION IS
induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
triple therapy maintenance immunosuppression can be given
Post-transplant prophylaxis
Life long PJP prophylaxis
CMV prophylaxis in D+/R-
Treat if LTBI diagnosed
HIV monitoring
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first
assays at 1 month after transplant and subsequent studies every 2-3 months for the first
year then every 3-6 months thereafter (1B)
• If patients have persistent HIV viraemia, drug-resistance testing is carried out to
determine treatment options (1D)
Choice of living versus deceased donor
Access to Live donor is same like non HIV
HIV donor is unsuitable for live donation
CONSENT
general rules applies here
Recipient is SUGGESTED to disclose HIV status to donor
Use of HIV-infected donors for HIV-infected recipients
DONORS with following parameters CAN DONATE
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to
brain injury
b) Information about the donor virus such as historical genotype patterns where
possible and current viral load
c) No history of virological failure or drug resistance (1D)
Summary
Background
HIVAN is the most severe form of CKD and commonest cause of ESRD in HIV positive patients in UK.
Patients with HIVAN are usually young (median age of 36 years) with severe immunodeficiency and with advanced CKD at time of diagnosis.
HAART may retard the progression but most patients will progress to ESRD within 10 years from time of diagnosis.
Kidney transplantation prior to the era of cART was disappointing with patient median survival of 4 years.
Antiretroviral treatment has made kidney transplantation in HIV positive patients feasible.
However it is complicated with high rates of acute allograft rejection which could be attributed due to lack of balance between immunosuppression and viral suppression.
The use of cART is associated with metabolic syndrome and diabetes mellitus.
Indications for kidney transplantation
Kidney transplantation in HIV patients with ESRD is associated with better survival rates than patients who remain on dialysis.
Studies have shown that in the carefully selected HIV positive patient patient survival and graft outcomes at 1 and 3 years are similar to the non-HIV population.
The following criteria should be met:
All potential kidney transplant recipients should be screened for HIV.
HIV is not a contraindication for transplantation.
Indication for pancreas transplantation
DM patients with controlled HIV infection in ESRD should be considered for simultaneous kidney- pancreas transplant.
Diabetic patients with severe hypoglycaemic awareness with stable HIV and kidney function should be considered for pancreas transplantation.
Contraindications to transplantation
Absolute contraindications
1. Uncontrolled HIV infection low CD 4 counts and detectable HIV viral load
2. Non-compliance to cART either due to psychiatry illness, psychosocial factors or substance abuse.
3. Multi drug resistance HIV with no available cART.
4. Positive CDC crossmatch.
5. Serious ongoing infections including documented history of PML.
6. Pregnancy
7. Active malignancy
Relative contraindications
1. Positive FXCM
2. ABO incompatibility.
3. Treated malignancy
4. Marked obesity BMI>35kg/m2
5. HTLV infection
6. Chronic liver disease
HIV specific assessment
1. All transplant recipients to due immunological and virological evaluation that includes CD4 counts, HIV RNA, prior cART AND HIV resistance profile. Ideally the CD4 counts should be >200cells/ul (liver transplantation>100 cells/ul) with undetectable HIV RNA, however in carefully selected patients a detectable HIV RNA/CD<200cells/ul may be accepted.
2. Antiretrovirals that are nephrotoxic or those with significant drug interactions with immunosuppression should be avoided.
3. Recipients should undergo testing for latent TB with IGRA and those with positive test treated prior to transplantation.
4. Recipients should undergo screening for syphillis, HSV,VZV,CMV,EBV,HTLV, HBV, HCV, toxoplasmosis and strongyloides stercolaris in endemic areas.
Pre-transplant immunisation
All non-immunised patients should receive Hepatitis B, Hepatitis A and VZV vaccination if CD4 count>200cells/ul.
All patients should receive pneumococcal and DTP vaccine.
Consideration of drug-drug interaction
Pre-emptive switching from PI in order to minimise drug interactions.
Continuation of cART during the peri-operative period.
Full and current medical review to be carried out twice yearly and after every therapeutic decision point.
Induction and maintenance therapy.
The recommended induction therapy is IL2RA .
Maintenance therapy should be triple therapy.
Acute rejection in HIV positive should be managed was the same way as HIV negative.
Post-transplant prophylaxis.
PCP prophylaxis should be offered lifelong.
Toxoplasmosis prophylaxis should be offered to seropositive patient with CD4 <200cells/ul or a recipients who received from seropositive donor for lifelong.
CMV prophylaxis should be offered for D+/R-
MAC prophylaxis should be offered to patients with CD4 counts<50cells/ul.
Monitoring allograft function
Post-operative care for HIV positive kidney transplant recipients would be similar to non-HIV.
Monitoring HIV virological control
HIV RNA and CD4 counts should be monitored regularly with first assay at first month then ever 2-3 months in the first year then every 3-6 months thereafter.
Patients who received antibodies depleting agents will require more frequent monitoring.
If HIV viremia persists the patient should be tested for resistance.
Choice of living versus deceased donor
HIV infected patients should have same access to living donation as non-HIV.
Donors should be informed of factors that may heighten recipients morbidity and mortality risk, however disclosure of recipient HIV status is not mandatory.
HIV infected donors are unsuitable as living kidney donors.
Consent and confidentiality
Existing ethics guidelines for deceased and living donors should be followed.
Standard consent for HIV patients is similar to non-HIV patients.
Recipients is encouraged to disclose their status to donor.
Donors should be asked if there are any medical conditions that would make them change their decision to donate.
Living donors should be made aware that there is some information on medical and social factor on the recipient that will not be disclosed to them.
Summary of BTS guideline for kidney and pancreas transplantation in HIV infection
Introduction
Kidney transplantation in HIV-positive ESRD patients is considered the standard of care for the last 15 years with improved life expectancy due to the effective use of C ART since 1996 increased number of patients offered kidney transplantation with specific consideration and an increased number of centers offered transplantation and this guideline revised from the previous copy in 2016 based on the available current evidence this guideline will give a comprehensive summary of kidney and pancreas transplantation in this specific group of patients
transplantation in HIV-infected patients can be offered provided they fit the following eligibility criteria
1. Medically fit and life expectancy > 5 years, stable on ART for the last 3 months
2. Negative viral load < 50 copies for the last 6 months of FU with HIV specialist
3. Responsive to ART and no previous poor compliance or resistance to the therapy
4.CD4 count > 100 preferred above 200 cells /ml
5.No active infection for 6 months including opportunistic infection
6.No evidence of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Also suggested discussing with the patient and the HIV specialist the choice of ART before transplantation to avoid drug-drug interaction, especially with CNI and everolimus.
Indications for Pancreas Transplantation
Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Diabetic patients with severe hypoglycemia unawareness may offer solitary pancreas transplantation or islet transplantation if they have well-controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min)
absolute contraindication for kidney transplantation in HIV patients
. Active HIV disease with persistent viremia despite C ART
. Low CD4 count < 100 cell/ml for the last 6 months
. Active substance abuse and major psychiatric illness
. Multiple ART resistance
. Positive CDC crossmatch
. Active infection including active TB treatment
. Active malignancy on treatment, or disseminated tumor
. pregnancy
Relative contraindications to kidney transplantation:
1. Positive flow cytometric crossmatch (FCXM) (1D)
2. Blood-type incompatibility (2D)
3. Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
4. Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
5. Chronic liver disease (2D)
6.Marked obesity (BMI >35 kg/m2) (2D)
7. HTLV infection (1D)
HIV-specific assessment
1 Specific immunovirological screens like CD4 count, HIV RNA viral load
2. Review the drug history including the ART dosing duration any previous intolerance, side effect, or resistance
3. serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human T-cell leukemia virus
and Toxoplasma gondii (1D)
4. screen for LTBI or ACTIVE TB and treat accordingly to insure eradication of active TB.
5. All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA /
hepatitis C RNA levels quantified and investigated for the presence of liver cirrhosis
6. HBV screen with HBs Ag positive should be tested for hepatitis B DNA (1B)
7. all HIV positive candidates need to be assessed for the presence of
cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial
neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to
transplantation (1D
8. Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those
with evidence of active HCV replication (1C)
9. patients with a history of Castleman’s disease, human
herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)-
related lymphoma (1D)
10. Transplant candidates from endemic regions are screened for Strongyloidiasis stercoralis infection prior to transplantation (2D)
11.avoid nephrotoxic ART and ART with PI activity due to drug-drug interaction with other IS
For pancreas transplant further assessment
First, discuss with the patient that needs to be assessed in care with good experience in kidney transplant and should be informed about the limited experience for pancreas transplantation in a such specific group of patients
1. Diabetic assessment (for hypoglycemic unawareness, peripheral neuropathy, &
autonomic neuropathy)
b) Vascular assessment (ultrasound assessment of leg vessels, and consider non-contrast CT of the aorta and iliac arteries), risk of vascular thrombosis
c) Consideration of a more extensive cardiac assessment (2C)
vaccination prior to transplantation
1. HBV vaccination for those with HBS ab < 10 iu
2. HAV vaccination
3. Pnemovax 23 for all non-immune
4.Seasonal influenza vaccine (annual)
5.Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
We suggest also Diphtheria, tetanus, and pertussis (DTP) vaccine is administered to all patients (2D)
• Measles, mumps, and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D)
• Human papillomavirus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C).
Induction and maintenance IS for HIV recipients
Induction therapy is preferred with an interleukin-2
receptor antagonist (IL-2RA)
Maintenance
triple immunosuppression steroids, a calcineurin inhibitor (CNI) and
an anti-proliferative agent (1C)
• Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant chemoprophylaxis
1, life -long for PJP
2. CMV D +VE /R+ve prophylaxis for minimum 3 months (1A).
3. CMV seropositive transplant recipients receive either prophylaxis against CMV infection
or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A).
4. patient with a previous history of LTBI or previous history of treated active TB should be assessed for latent reactivation after a history of exposure post-TX and follow the same NCE GUIDLIEN for latent TB treatment
5. Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong
prophylaxis (2C)
6. Previously treated TB infection no need for TB prophylaxis or reassessment unless there is a suspected risk of re-exposure
7. Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6
months (2D).
post-transplantation HIV viral load monitoring
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays 1 month, and subsequent studies every 2-3 months for the first year and then every 3-6 months thereafter (1B) • If patients have persistent HIV viremia, drug-resistance testing is carried out to determine treatment options (1D
Kidney and pancreas transplantation in patients with HIV
Guidelines advised by British society for transplantation, aiming to cover all aspects of assessment, selection and management of people living with HIV recipients.
Indication for kidney transplantation
Recommendations
· Screen all Kidney transplant recipients for HIV (1D)
· HIV is not a contra indication for KT (1B)
· Waist list if ;
§ On ART (1D)
§ CD 4 cell > 200cells/microL(1B)
§ Undetectable HIV RNA foe last 6 months (1B)
§ NO opportunistic infection in last 6 months (1B)
§ No PML, Intestinal cyptosporidosis or lymphoma(1B)
Suggestion
· ART to be discussed before transplantation(Not graded)
Indications for Pancreas Transplantation
Recommendations
· Pancreas recipients should be assessed in center experience in KT for HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded)
Suggestions
· Diabetics with controlled HIV infection can be considered for,
· Simultaneous KPT(2D)
· If they have severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if kidney function is stable. (Not graded)
Contraindication to transplantation
· Absolute contraindication to kidney transplantation in patients with HIV
1. Uncontrolled HIV infection CD4< 100cell/ul(1C)
2. No adherence to treatment (1D)
3. Resistance to available ART drugs (1D)
4. Positive CDC cross match(1D)
5. Serious ongoing/recurrent infection/PML (1D)
6. Active/ disseminated malignancy(1D)
7. Pregnancy
· Relative contraindications to kidney transplantation in patients with HIV
1. Positive FCXM(1D)
2. ABOi (2D)
3. Treated malignancy / Kaposi sarcoma(2D)
4. CLD (2D)
5. BMI> 35KG/m2 (2D)
6. HLTV infection (2D)
7. Uncontrolled medical problem (2D)
General assessment
HIV specific assessment
· Evaluate virological and ART status (1D)
· If HIV RNA <200 copies/mL, considered Transplant if adherent with medications (1C)
· Serology for syphilis, HSV, EBV, CMV, VZV, HTCLV, Toxoplasma and Strongyloides (1D)
· TB screening & treatment prior to transplant (active/ Latent) with IGRA +/- TST (1C)
· Screened for viral hepatitis; If serology positive to confirm with DNA/RNA and to look for cirrhosis (1C)
· HBsAg positive patients to receive treatment and ensure viral suppression (1B)
· Screen & treat for cervical and/or anal neoplasia (1D)
· SOT can be considered in case HIV RNA suppressed & CD4 < 200 but >100 cells (2C)
· Avoid antiretroviral with nephrotoxic potential or drug-drug interactions.
· Anti-HBc positive “alone” recipients do not require prophylaxis unless reactivation risk is high.
Pancreas-specific assessment
Should be performed in experience center with HIV patients.
• Pancreas Transplant assessment in patients with HIV includes:
• Detailed diabetic assessment, vascular assessment& cardiac assessment (2C)
Pre-transplant immunization
Recommendation
• HBV vaccination of all patients if titer <10 mIU/mL (1B)
• HAV vaccine (for non-immune) (1D)
• PPV-23 (1B)
• VZV vaccine (non-immune) with CD4 >200 cells/μL (1C)
• Influenza vaccine annually (1B)
Suggestion
• DTP to all patients (2D)
• MMR to none immune Patients (2D)
• HPV for high risk (2C)
Consideration of drug-drug interactions
Recommendation
• To consider ART in the perioperative period (1D)
Suggestions
• Medication review as part of the assessment (Not graded)
• CNI trials to determine optimum doses (2D)
• Switching from PI regimens to minimize drug interactions (2D)
Induction and maintenance immunosuppression
Recommendation
• Induction therapy offered to All KTR with HIV-positive at time of Tx1C)
• Induction therapy is with IL-2RA (1B)
• Triple maintenance IS started at the time of kidney transplantation (1c)
Suggestion
• Acute rejection is treated the same way as HIV-negative KTR (2D)
Post-transplant prophylaxis
Recommendation
• Lifelong prophylaxis against PCP (1D)
• CMV prophylaxis; if CMV R-/ D+ for of 3 months (1A)
• Recipient CMV positive; either prophylaxis or surveillance and pre-emptive therapy for 3 months (1A)
• Assess and treat LTBI prior to transplantation, revaluate if new exposure history or symptoms develop, and treat as per NICE guidelines (1C)
Suggestion
• Toxoplasma lifelong prophylaxis if either donor is positive or recipient positive & CD4 <200 (2C)
• MAC prophylaxis; if CD4 count ≤ 50. To be stopped when the count is >100 cells/μL for 6months (2D)
Monitoring allograft function
Recommendation
• Follow the current guidelines for post-operative care of the KTR (Not graded)
Monitoring HIV virological control
Recommendation
• HIV RNA and CD4+ T-cell counts, at 1 month then 2-3 months for the first year then every 3-6 months (1B), more frequent if receiving antibody depleting to assess the need for prophylaxis (2D)
• If Viremia is persistent test for drug-resistance (1D)
Choice of living versus deceased donor
Recommendation
• Access to living donor KT should be the same as non-infected patients. (1B)
• HIV donors are unsuitable for donation (1D)
Suggestion
• Disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality
Recommendation
• Follow the same guidelines on the ethics for all donors (Not graded)
• Standard of consent should be the same (Not graded)
• Transplant team must be satisfied that donor consent is adequate (Not graded)
Suggestion
• Encourage the recipient to disclose HIV diagnosis to their donor (Not graded)
• Donors are asked about any condition cause them to change their decision to donate, without highlighting HIV (Not graded)
• Donors should be aware about that medical and social or confidential information about the recipient that is not disclosed (Not graded)
Use of HIV-infected donors for HIV-infected recipients
Recommendation
• Using HIV-infected organs is restricted to organs from DD with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Genotype patterns where possible and current viral load
c) No virological failure or drug resistance (1D)
• Recipients are counseled and give informed consent (1D)
Suggestion
• LD with HIV-infection are considered for donation (1D)
• The use of HIV+ organ is restricted to experience centers (Not graded)
⭐⭐⭐BTS guidelines; Kidney & Pancreas Transplantation in Patients with HIV
Summary:
· Kidney transplantation in HIV recipients:
o All potential kidney transplant recipients must be screened for HIV infection
o HIV per se is not an absolute contraindication for kidney transplantation, and should have access to living donor transplantation as non HIV cases provided that: if adherent to treatment, particularly combined anti-retroviral therapy (cART) + CD4+ T cell counts are stable in preceding 3 months at level >100 cells/µL (ideally > 200 cells/ µL) + undetectable HIV RNA in the previous 6 months + No opportunistic infections documented during the previous 6 months+ no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
o Choose appropriate therapy with HIV expert prior to transplantation (take care of drug-drug interaction).
· Absolute Contraindication to transplantation in HIV;
o Uncontrolled HIV infection (CD4+ T cell levels persistently <100).
o Persistent +ve PCR in last 3 months.
o None adherence to therapy (psychiatric problem-drug abuse).
o Multi-drug resistant HIV.
o +ve CDC crossmatch.
o Active infection/malignancy or pregnancy.
· Relative contraindication to transplantation in HIV;
o Positive FCXM, ABOi or increased HLA mismatch (as they need desensitization protocols that flare up HIV).
o Treated malignancy, including extracutaneous Kaposi sarcoma,
o Severe and/or uncontrolled medical problems that will shorten the patient’s life expectancy as Chronic liver disease, Marked obesity (BMI >35), HTLV infection.
· So 3 important parameters in follow up and monitoring of HIV cases (HIV PCR, any viral resistance pattern, CD4 T cell count, treatment used and adherence) should be done prior to transplantation to determine if possible to transplant or not (and 1 month after transplantation, then every 3 months during 1st year, then every 3-6 months thereafter).
· Additional Testing /screening for syphilis, HSV, EBV, CMV, VZV, human T-cell leukaemia virus and Toxoplasma gondii, latent TB (Quantiferron test/IGRA).
· Latent TB should be screened for active TB (smear with Zn stain, CXR, geneXpert, rapid culture on BACTEC system), if positive treatment is essential prior to transplantation. If just latent infection is treated with prophylactic anti TB regimen prior to transplantation. If exposure occurs after transplantation, reevaluation is essential.
· Screen for hepatitis as: HB S Ag or HCV antibody, then PCR quantified and Us screening for liver cirrhosis. (HBV infection must be treated prior to transplantation). If Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but better avoid lymphodepletion therapy.
· screen for Strongyloides stercoralis infection prior to transplantation in transplant candidates from endemic regions.
· Screen for cervical/anal cancer, cases with cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation.
· Nephrotoxic antiretrovirals (specific tenofovir formulations and atazanavir) are better avoided in kidney transplantation, Antiretrovirals with significant drug-drug interactions with CNI (ritonavir and cobicistat) are avoided in the setting of SOT.
· Pancreas transplantation (either isolated as in uncontrolled diabetic state or combined with kidney in diabetic nephropathy).
o Kidney and/or pancreas transplantation is contraindicated in patients with liver cirrhosis, active HCV replication, Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or EBV- related lymphoma.
· Pre-transplant immunization:
o HBV vaccine is administered to all non-immune patients (HBV S antibody titres <10 mIU/mL).
o HAV vaccine is administered to all non-immune patients
o Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients
o Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL
o Annual Influenza vaccine.
o DPT and MMR to all none immune cases.
· Drug-drug interaction between CNI and anti-retroviral therapy;
o Try CNI before transplantation to adjust dose.
o Avoid protease-inhibitors (PI)-based antiretroviral.
o Best in KT is to use DNA integrase inhibitors.
· Immunosuppressive therapy: induction with basiliximab and tacrolimus based triple maintenance IS therapy with steroids +MMF. In addition, treatment of rejection episodes is the same as HIV –ve recipients.
· Chemoprophylaxis against PJP and CMV is the same as none HIV (CMV D+/R-) should receive 3-months prophylaxis, while CMV D+/R+ should have PCR monitoring and preemptive therapy).
· Toxoplasma IgG seropositive recipients with a CD4+ count <200, with positive donor (receive life-long prophylaxis).
· Donation to HIV +ve recipient needs disclosure about the recipient’s morbidity and mortality risk (better by the recipient himself), but not the recipient’s HIV other medical or social status, with standard obtaining of
· HIV + ve recipient is accepted, but consider absolute CI to living donation.
· Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors and to HIV +ve recipients with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Information regarding donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance to decrease risk of transmission of viral resistance.
· Recipients are counselled and obtain informed consent both at the time of listing and at the time of transplantation.
· Patients with HIV-infection are unsuitable to be living kidney donors (1D)
· HIV+ organ use is restricted to centers that have experience in transplanting HIV+ patients (Not graded)
I appreciate your clinical approach.
BackgroundAs per a report from 2013, 108,000 people were living with HIV in the UK. The use of combination antiretroviral therapy (cART) has led to a decrease in opportunistic infections and death. Immunodeficiency is an important risk factor for chronic kidney disease (CKD) and end-stage kidney disease (ESRD).
HIV-associated nephropathy (HIVAN) is the most severe form of CKD and one of the commonest cause of ESRD in HIV-positive patients. Patients with HIVAN are typically young (mean age 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median estimated glomerular filtration rate [eGFR] 21 mL/min/1.73m2) at diagnosis.
Suppressing HIV replication may improve or stabilize kidney function, but a majority of patients may still progress to ESRD. Kidney transplantation in HIV-positive patients is complicated due to a high rate of acute allograft rejection. However, immune suppression is noted to be well tolerated, with fewer patients experiencing opportunistic infections.
HIV infection is not associated with an increased risk of diabetes mellitus. However, the use of cART has been associated with metabolic syndrome and diabetes mellitus.
Indications for kidney transplantationRecommendations
Wait-listing HIV patients should only occur if:
It is suggested that the most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication.
RationaleIt is noted that select patient groups have shown positive results after transplantation. It is recommended that the following criteria should be met:
Patients demonstrate overall concordance with recommended treatment, and with cART therapy in particular
CD4+ T cell levels are a minimum of 100 cells/µL and ideally >200 cells/µL and have been stable during the last 3 months
HIV RNA has been undetectable during the last 3 months
No opportunistic infections have occurred during the last 6 months
No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
The reported higher rejection rate in some studies can potentially be attributed to the difficulty in obtaining a good balance between immunosuppression and controlled viral replication. It is suggested that the most appropriate anti-retroviral therapy for an individual patient should be discussed with the HIV/infectious disease team before transplantation.
Indications for pancreas transplantationRecommendationsIt is suggested that diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation, and that diabetic patients with severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min).
It is recommended that such patients are assessed by a center with experience in kidney transplantation in HIV-positive patients and in solitary pancreas or islet transplantation.
RationaleThere is relatively little experience with simultaneous pancreas–kidney transplantation in HIV-positive patients with diabetes mellitus. Extrapolating the results seen in selected HIV-positive patients receiving kidney transplants, it is recommended that diabetic patients with kidney failure and controlled HIV infection may be considered for simultaneous kidney and pancreas transplantation.
In the general population, if a patient suffers from life-threatening hypoglycemic unawareness despite good diabetic care, islet cell transplantation or solitary pancreas transplantation may be considered. Unfortunately, there is no published experience of this type of transplantation in HIV-positive patients. If transplantation is considered, it is recommended that patients are assessed by a center that regularly performs both solitary pancreas or islet transplantation and also kidney transplantation in HIV-positive patients.
Contraindications to transplantationRecommendationsIt is recommended that the following are absolute contraindications to kidney transplantation in patients with HIV:
It is suggested that the following are relative contraindications to kidney transplantation:
General assessmentRecommendation
RationaleThere is no evidence that general assessment for transplant candidacy should be different for HIV-infected and non-HIV-infected kidney and pancreas transplant candidates.
HIV-specific assessmentRecommendationsIt is recommended that:
It is suggested that in selected cases:
RationaleIt is important to ensure that infectious complications post-transplantation are minimized through screening, immunisation and/or the provision of treatment and to formulate a management plan that allows the safe co-administration of combination antiretroviral therapy (cART) and immunosuppression.
The 2005 BTS guidelines proposed that HIV-positive patients who are considered for kidney transplantation should have CD4 cell counts above 200 cells/µL, undetectable HIV RNA levels, and future antiretroviral options. It is unclear whether patients with CD4 cell counts below 200 cells/µL but with fully suppressed HIV RNA levels are at greater risk of infectious complications post-transplantation. Therefore, it appears that, in carefully selected cases, solid organ transplantation may also be an option for patients with fully suppressed HIV RNA and an absolute CD4 cell count below 200 cells/µL. The appropriate cART regimen for patients awaiting solid organ transplantation is determined by the presence of HIV resistance mutations and the recipient’s ability to tolerate specific antiretrovirals.
It is also important to know whether potential transplant recipients have had exposure to the common herpes viruses: herpes simplex virus (HSV); Epstein-Barr virus (EBV); cytomegalovirus (CMV); and varicella zoster virus (VZV).
Solid organ transplant recipients are at increased risk of developing tuberculosis (TB). TB post-transplantation is a serious complication; the diagnosis of TB is challenging and its treatment complex in patients on antiretroviral and immunosuppressive therapy.
The prevalence of hepatitis B (HBV) and hepatitis C (HCV) is increased in HIV-positive patients. There are high rates of liver disease progression (cirrhosis, hepatocellular carcinoma) that have been reported in untreated HBV co-infected patients who underwent kidney transplantation. Among HIV-positive kidney transplant recipients, a higher early mortality has been observed for those co-infected with HCV.
The incidence of human papilloma virus (HPV)-associated cancer and Kaposi sarcoma (KS) are markedly increased in both HIV-positive patients and kidney transplant recipients.
Pancreas-specific assessmentRecommendationsIt is recommended that pancreas transplantation assessment in patients with HIV includes:
It is recommended that assessment of these patients is performed in a center that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation and that the transplant candidate is carefully counselled and informed that there is currently relatively little experience of pancreas transplantation in HIV-infected patients.
RationaleThe patients assessed for pancreas transplantation should ideally also be assessed for the presence of hypoglycemic unawareness, peripheral neuropathy, and autonomic neuropathy. A C-peptide level must be measured to determine whether the transplant candidate has type I or type II diabetes. Most patients will require a more extensive vascular assessment to include ultrasound assessment of leg vessels, and possibly non-contrast CT assessment of the aorta and iliac arteries.
Pre-transplant immunizationRecommendationsAs part of the work-up for solid organ transplantation it is recommended that:
It is suggested that:
It is also recommended that influenza vaccine is administered annually to patients awaiting solid organ transplantation.
RationaleHBV vaccination significantly reduces the risk of incident HBV infection in HIV positive persons. It is recommended to immunize those with a high risk of hepatitis A infection. It is safe and well tolerated in HIV-infected patients and those with end-stage kidney disease.
Pneumococcal vaccination is recommended for all HIV positive patients with CD4 cell counts >200 cells/µL, and for those with CD4 cell counts <200 cells/µL if there are additional risk factors such as chronic kidney and liver disease or diabetes mellitus. Vaccination should be repeated every 3-5 years.
HIV-positive persons and solid organ transplant recipients have a higher frequency of zoster than the general population. Guidelines recommend VZV vaccination for asymptomatic, VZV IgG seronegative HIV positive adults with a CD4 cell count >400 cells/µL and suggest that vaccination may also be considered for patients with CD4 counts of 200-400 cells/µL who are stable on cART.
Diphtheria, tetanus and pertussis vaccine is safe and it is a recommended vaccination for all HIV-positive persons in accordance with standard recommendations. And for patients who have been previously vaccinated, a booster dose should be administered.
Guidelines recommend that HIV-positive persons be screened for measles IgG and offered MMR vaccine if they are measles IgG seronegative and asymptomatic with a CD4 count >200 cells/µL. Influenza vaccination is recommended for all HIV-positive patients.
Consideration of drug-drug interactionsRecommendations
It is suggested that all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource.
Rationale The general objectives for the preparation for solid-organ transplantation are to ensure that all medicines are reviewed prior to transplantation for potential drugdrug interactions and that the recipient receives optimal doses of calcineurin inhibitors (CNI) to reduce the risk of graft rejection. The first step in preventing harm, and in recognising medication error when it occurs, is to ensure current and complete medication recording. To optimise CNI concentrations following transplantation and help manage the drug-drug interactions between immunosuppressant drugs and ART, a dose-finding trial of CNI immunosuppression with therapeutic drug monitoring may be considered as part of the workup for solid organ transplantation, and is recommended in patients whose cART contains protease-inhibitors. It is critical that both clinicians and patients are aware of the implications of the drug interactions between cART and immunosuppressants, and that the timing of doses and immunosuppressant concentrations, as well as drug dosages and frequencies, are properly communicated and documented.
Induction and maintenance immunosuppressionIt is recommended:
It is suggested that:
Rationale The evidence base for the use of lymphocyte-depleting agents in HIV-positive kidney transplantation is very limited. In non-HIV kidney transplant recipients, there is good evidence to support the use of tacrolimus for maintenance therapy, over ciclosporin in terms of reduced acute rejection and graft survival. There is some evidence to suggest that ciclosporin, and in particular mTOR inhibitors may have an anti-HIV effect including, in the case of mTORs, decreased CCR5 expression and viral reactivation. There is insufficient data in HIV-positive patients to make absolute recommendations on the best maintenance immunosuppressive regimen.
Post-transplant prophylaxisRecommendationsIt is recommended that:
It is suggested that:
RationaleIn general, anti-Pneumocystis prophylaxis is recommended for all non-HIV-infected solid organ transplant recipients for at least 3-6 months post-transplant. Toxoplasmosis in transplant recipients can occur through ingestion of contaminated food or water, after receiving an infected allograft, or by reactivation of latent infection.
To avoid primary infection, transplant recipients should avoid contact with undercooked meat, soil, water or animal faeces that might contain toxoplasmosis cysts.
The routine use of co-trimoxazole for post-transplant PCP prophylaxis has decreased the risk of toxoplasmosis and is the most effective prophylaxis against this parasite.
In HIV-positive patients, co-trimoxazole 960 mg once daily is recommended as first line prophylaxis.
The two major strategies for cytomegalovirus (CMV) prevention are antiviral prophylaxis and pre-emptive therapy. Valganciclovir is the preferred prophylactic agent, and in general should be started as early as possible and within the first 10 days after transplantation.
Monitoring allograft functionRecommendationsIt is recommended that existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease.
It is suggested that local practice for monitoring of the pancreas allograft is followed.
RationaleThere is no evidence that post-operative care should be different for HIV-infected and noninfected kidney and pancreas transplant candidates.
Monitoring of HIV virological controlRecommendations
It is suggested that more frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis.
RationaleAnti-viral treatment that is insufficient to completely suppress viral replication imposes a selective pressure that may result in the emergence of drug-resistant viral escape mutants. HIV drug resistance testing is thus part of the standard management of patients in whom viral replication is not suppressed.
Choice of living versus deceased kidney donor RecommendationsIt is recommended that patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients and that patients with HIV infection are unsuitable to be living kidney donors.
It is suggested that potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory.
RationaleLiving kidney donation yields superior outcomes relative to deceased donor transplantation. A recent survey found that HIV-infected patients have less knowledge about living donor kidney transplantation, have more concerns about living donor kidney transplantation, and are less willing to pursue living donor kidney transplantation than those without HIV.
Most perceive their HIV status to be a barrier to living donor kidney transplantation. Given the increased risk of kidney disease in HIV-infected patients the use of such patients as living kidney donors, even with well-controlled HIV, is not recommended.
Consent and confidentialityRecommendationsIt is recommended that:
It is suggested that:
RationaleIt is recommended that all health professionals involved in transplantation should acknowledge the wide range of complex moral issues that are associated with this area of clinical practice and ensure that good ethical practice consistently underpins clinical practice to achieve optimum outcomes.
Use of HIV-infected donors for HIV-infected recipients Recommendations:It is recommended that transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
It is also recommended that recipients are counselled and give informed consent both at the time of listing and at the time of transplantation and that patients with HIV-infection are unsuitable to be living kidney donors.
It is suggested that HIV+ organ use is restricted to those centers that have experience in transplanting HIV+ patients.
RationaleThere is a risk of transmission of opportunistic infection from the donor. HIV infection can cause organ damage such as chronic kidney disease due to HIV-associated nephropathies, and the recipient should be counselled about this risk. Preimplantation biopsies may be considered to detect donor disease. Given the increased risk of kidney disease in HIV-infected patients, the use of such patients as living kidney donors, even with well-controlled HIV, is not recommended.
That is a very detailed reply.
Kidney & Pancreas Transplantation in HIV Patients
HIV patients who might be listed for kidney transplantation have the following criteria:
– With cART, CD4 count > 100 (preferably > 200), stable > 3 M, no opportunistic infection in the last 6 M, and undetectable HCV RNA
No prior history of lymphoma, chronic intestinal cryptosporidiosis, or progressive multifocal leukoencephalopathy is required.
When HIV is stable, these are the reasons for a pancreas transplant:
SPK with controlled HIV
Pancreas with severe low blood sugar and an eGFR of more than 40mL/min
Absolute contraindication to transplantation of HIV patients
Uncontrolled HIV infection, a low CD4 count that doesn’t go up, and a viral load that can be seen.
Uncontrolled HIV infection that is resistant to multiple drugs
Positive complement-dependent cytotoxic (CDC) crossmatch
Serious or recurrent infections, cancer, or being pregnant
Relative contraindication to transplantation of HIV patients:
a) Positive flow cytometric crossmatch
b) ABO incompatibility
c) Treated malignancy, including extracutaneous Kaposi sarcoma
d) Severe and/or uncontrolled medical problems that are unlikely to improve after
kidney transplantation and will shorten the patient’s life expectancy
e) Chronic liver disease
f) Marked obesity (BMI >35 kg/m)
g) HTLV infection
Pretransplant assessment
– HLA-B5701 status, CD4 cell count, HIV RNA level, current and previous antiretroviral therapy, HIV resistance profile, and HIV resistance profile – Syphilis, HSV, HZV, EBV, CMV, varicella zoster virus, HTCL virus, and Toxoplasma gondii
– TB screening: use an interferon test to check for latent infection -gamma test with or without a concomitant Mantoux test; in the event of a positive result, seek for active infection and treat both active and latent infection as in the general population.
– Screening and treatment for viral hepatitis
– check for occult malignancies in particular genito-urinary neoplasia
– In endemic locations, check for Strongyloides stercoralis
Immunization prior to transplant
HBV surface antibody titres lower than 10miu/ml in non-immune individuals should necessitate HEP B vaccine.
All eligible patients will receive the Hep A and pneumococcal vaccines.
VZV will be administered to non-immune patients with CD4 counts above 200 cells per ul, and those awaiting SOT will receive the influenza vaccination yearly.
All eligible patients receive DPT.
MMR is given to those who have never had the measles, whereas HPV is given to people who are at risk of getting the virus.
Drug–drug interaction suggestion
A complete and current medication review as part of solid organ transplantation assessment, done at least twice a year and at crucial treatment decision points
A calcineurin-inhibitor dose-finding trial before solid organ transplantation to estimate post-transplant dosages.
If possible, avoid enhanced protease-inhibitors (PI)-based antiretroviral regimens to reduce medication interactions.
All clinical correspondence includes a footer pointing practitioners to the Liverpool HIV Drug Interactions Portal.
Induction and maintenance immunosuppression
All HIV-positive kidney transplant candidates get induction treatment.
Most HIV-positive individuals receive interleukin-2 receptor antagonist induction treatment.
HIV-positive kidney transplant recipients receive steroids, a calcineurin inhibitor, and an anti-proliferative drug for maintenance immunosuppression.
HIV-positive kidney transplant recipients are treated the same for acute rejection.
Post-transplant prophylaxis
HIV-positive transplant recipients receive lifetime Pneumocystis pneumonia prevention.
CMV seronegative recipients of organs from CMV-positive donors should receive cytomegalovirus prophylaxis for at least three months.
CMV seropositive transplant recipients get either prophylaxis or PCR surveillance and pre-emptive medication for 3 months.
Healthy transplant patients who were not screened and treated for Mycobacterium TB latent infection or illness before transplantation should be assessed as recommended.
Transplant patients who are well and were assessed and treated for Mycobacterium TB latent infection or illness before transplantation do not need reassessment unless they have been exposed to tuberculosis.
According to NICE TB contact tracing recommendations, transplant patients who are re-exposed to tuberculosis should be tested for latent infection and illness.
Toxoplasma IgG seropositive receivers with a CD4+ count <200 cells/μL or organ recipients from seropositive donors receive lifelong prophylaxis.
If there is a solid history of treated TB infection, symptom evaluation and chest X-ray are sufficient diagnostics, and TB prophylaxis is not needed until re-exposure is suspected.
Prophylaxis against MAC is recommended when the CD4+ level is fewer than 50 cells/μL and ceased after 6 months when it is greater than 100.
Allograft monitoring
All HIV-positive kidney transplant recipients follow post-operative instructions.
Pancreas allograft monitoring based on local practice and protocols.
HIV virus surveillance
Quantitative HIV RNA and CD4+ T-cell counts are measured at 1 month after transplant, then every 2-3 months for the first year, then every 3-6 months after that.
Drug-resistance testing determines treatment options for HIV viremia.
Depleting antibodies may require more frequent CD4 count monitoring to evaluate anti-infective treatment.
HIV-positive donors and recipients
HIV viral load <50 copies/mL and CD4 count >200/μL for at least six months prior to brain damage.
Genotype patterns and viral load of the donor virus.
No pharmacological or viral failure.
Both donor and recipient are counseled and give informed consent.
HIV-positive people cannot donate kidneys.
Only HIV+ transplant centers can use HIV+ organs.
I appreciate your clinical approach.
• The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
HIV-specific assessment
• All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
• Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
• Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
• Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing
strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
• Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
• Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
• Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
• All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis(1C)
• All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
• Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
Pre-transplant immunisation
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
• Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
• Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
• Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/μL (1C)
• Influenza vaccine is administered annually to patients awaiting solid organ
transplantation (1B)
Consideration of drug-drug interactions
• Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
Induction and maintenance immunosuppression
• All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
• For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
Post-transplant prophylaxis
• HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
• Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
• CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
Monitoring allograft function
• Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
Monitoring of HIV virological control
• Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
• If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
Choice of living versus deceased donor
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D
Consent and confidentiality
• Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
• The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
• Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded)
Use of HIV-infected donors for HIV-infected recipients
• Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Information about the donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
• Patients with HIV-infection are unsuitable to be living kidney donors (1D)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Summary of the article
Kidney & Pancreas Transplantation in Patients with HIV
1. Indications for Kidney transplantation
We recommend that:
a) All potential kidney transplant recipients are screened for HIV infection (1D)
b) HIV per se is not a contraindication for kidney transplantation (1B)
c) HIV-positive patients are wait-listed only if:
I. They are concordant with treatment, particularly cART therapy (1D)
II. Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months (1B)
III. HIV RNA has been undetectable during the previous 6 months (1B)
IV. No opportunistic infections have occurred during the previous 6 months (1B)
V. They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that:
· The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
2. Indications for Pancreas Transplantation
We recommend that:
· Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded)
We suggest that:
a) Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded).
3. Contraindications to transplantation
We recommend that: The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
We suggest that: The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
4. General assessment
We recommend that:
· Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded)
5. HIV-specific assessment
We recommend that:
a) All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
b) Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
c) Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
d) Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
e) Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
f) Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
g) Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
h) All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
i) All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
j) Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
We recommend against:
a) Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
b) Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1D)
We suggest that:
a) In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/μL but above 100 cells/μL (2C)
b) Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded)
c) Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D)
d) Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
e) Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
6. Pancreas-specific assessment
We recommend that:
a) Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C)
b) Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded)
We suggest that:
Pancreas transplantation assessment in patients with HIV includes:
a) Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy)
b) Vascular assessment (ultrasound assessment of leg vessels, and consider non- contrast CT of aorta and iliac arteries)
c) Consideration of a more extensive cardiac assessment (2C)
7. Pre-transplant immunisation
We recommend that:
a) Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
b) Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
c) Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
d) Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/μL (1C)
e) Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
We suggest that:
a) Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
b) Measles, mumps and rubella (MMR) vaccine is administered to all patients who are non-immune to measles (2D)
c) Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition(2C)
8. Consideration of drug-drug interactions
We recommend:
· Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
We suggest:
a) A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
b) A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
c) Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
d) That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
9. Induction and maintenance immunosuppression
We recommend that:
a) All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
b) For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
c) HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
We suggest that:
· Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
10.Post-transplant prophylaxis
We recommend that:
a) HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
b) Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
c) CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
d) Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
e) Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need re- assessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
f) Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C)
We suggest that:
a) Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/μL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
b) Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
c) Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/μL, and it be stopped when the CD4 count is >100 cells/μL for 6 months (2D)
11.Monitoring allograft function
We recommend that:
· Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
We suggest that:
· Local practice for monitoring of the pancreas allograft is followed (Not graded)
12.Monitoring of HIV virological control
We recommend that:
· Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
· If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
We suggest that:
· More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
13.Choice of living versus deceased donor
We recommend that:
a) Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
b) Patients with HIV infection are unsuitable to be living kidney donors (1D)
We suggest that:
· Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
14.Consent and confidentiality
We recommend that:
a) Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
b) The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
c) Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded)
We suggest that:
a) Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
b) All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
c) All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
d) All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
15.Use of HIV-infected donors for HIV-infected recipients
We recommend that:
a) Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with: Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
I. HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
II. Information about the donor virus such as historical genotype patterns where possible and current viral load
III. No history of virological failure or drug resistance (1D)
b) Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
c) Patients with HIV-infection are unsuitable to be living kidney donors (1D)
We suggest that:
· HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded).
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Kidney & Pancreas Transplantation in Patients with HIV,
BTS, second edition 2015
Indications for Kidney transplantation
HIV is not a contraindication for kidney transplantation.
HIV-positive patients are wait-listed only if:
Indications for Pancreas Transplantation
Absolute Contraindications to transplantation
Relative contraindications to kidney transplantation
HIV-specific assessment
Pre-transplant vaccination include:
· HBV and HAV vaccine, Pneumococcal polysaccharide vaccine, Influenzas vaccine, VZV vaccine is administered to patients with CD4 cell counts >200 cells/µL
Induction and maintenance immunosuppression
Post-transplant prophylaxis
Monitoring kidney function post transplantation
· Should follow the existing guidelines
Monitoring of HIV virology
Quantitative HIV RNA and CD4+ T-cell counts should be measured at 1 month after transplant and every 2-3 months for the first year then every 3-6 months later on.
If persistent HIV viraemia, then drug-resistance testing should be performed.
Choice of living versus deceased donor
Consent and confidentiality
Use of HIV-infected donors for HIV-infected recipients
· Patients with HIV-infection are unsuitable for living kidney donation.
· Deceased donors should have HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury.
· If possible, Information such as genotype and current viral load should be obtained.
· Should have no history of virological failure or drug resistance.
Kidney & Pancreas Transplantation in Patients with HIV
British Transplantation Society Guidelines 2015.
Indications for Kidney transplantation
They recommend that:
All potential kidney transplant recipients are screened for HIV infection (1D)
As HIV itself not a contraindication for kidney transplantation (1B)
There are specific criteria for HIV-positive patients listed on waiting list such as :
a) patients who are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma (1B)
Indications for Pancreas Transplantation
They suggest that:
• Simultaneous kidney and pancreas transplantation for diabetic patients in renal failure and with controlled HIV infection (2D)
• Diabetic patients with severe hypoglycemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded)
Contraindications to transplantation
They recommend that:
• Absolute contraindications to kidney transplantation in patients with HIV are :
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, including documented history of PML & active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
f) Pregnancy (1D)
They suggest that:
• The following are relative contraindications to kidney transplantation:
a) Positive flow cytometry crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extra cutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after
kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease and marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
General assessment
HIV-specific assessment:
They recommend that:
• All transplant candidates should reviewed by CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
• Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
• Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Monteux test(1C)
• Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation and also latent TB (1C)
• Screening for HBV and HCV and treatment for positive cases (1C)
• Screening for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
We recommend against:
• Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication and a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1C)
We suggest that:
• In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/μL but above 100 cells/μL(2C).
• Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
• Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, unless lympho-depletion therapy given) (2D)
Pancreas-specific assessment
They suggest that:
• Pancreas transplantation assessment in patients with HIV includes:
a) Diabetic assessment (for hypoglycemic unawareness, peripheral neuropathy, &
autonomic neuropathy)
b) Vascular assessment (ultrasound assessment of leg vessels, and consider non-contrast CT of aorta and iliac arteries)
c) Consideration of a more extensive cardiac assessment (2C)
Pre-transplant immunization
They recommend vaccination:
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titers <10 mIU/mL) (1B)
• Hepatitis A virus (HAV) vaccine, Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
• Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/μL (1C)
• Influenza vaccine is administered annually to patients awaiting solid organ
transplantation (1B)
They suggest that:
• Diphtheria, tetanus and pertussis (DTP), (MMR) vaccine is administered to all patients (2D)
Consideration of drug-drug interactions
They recommend:
• Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
We suggest:
• A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
• Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimize drug interactions (2D)
Induction and maintenance immunosuppression
We recommend that:
• All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
• Induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
We suggest that:
• Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
We recommend that:
• HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
• Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
They suggest that:
• Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/μL or any
recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong
prophylaxis (2C)
• Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/μL, and it be stopped when the CD4 count is >100 cells/μL for 6 months (2D)
Monitoring allograft function
We recommend that:
• Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
We suggest that:
• More frequent monitoring of CD4 count may be necessary in patients receiving
depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living versus deceased donor
We recommend that:
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D)
We suggest that:
• Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality
We recommend that:
• The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
• Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded)
We suggest that:
• Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
• All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
• All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
Use of HIV-infected donors for HIV-infected recipients
We recommend that:
• Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Information about the donor virus such as historical genotype patterns where
possible and current viral load
c) No history of virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
• Patients with HIV-infection are unsuitable to be living kidney donors (1D).
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney & Pancreas Transplantation in Patients with HIV (JAn 2017)
Indications for Kidney transplantation HIV patients can be listed for Tx if they are stable as follow:
Indications for Pancreas Transplantation with stable HIV:
Contraindication absolute
Uncontrolled HIV infection, persistent low CD4 count and detectable viral load.
Multi-drug resistant uncontrolled HIV infection
Positive complement-dependent cytotoxic (CDC) crossmatch
Serious ongoing or recurring infection, cancer or pregnant
Contraindication relative: CLD, obese, treated Malig, positive flow cytometry and ABO incompatibility
Assessment
Pre-transplant immunisation HAV, HBV, influenza, pneumococcal, VZV, DPT, MMR, HPV
Drugs:
A) ARV
Avoid ARV with nephrotoxic potential ( tenofovir and atazanavir)
Avoid those with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat)
Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org)
B) dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
C) Induction and maintenance immunosuppression
Induction with interleukin-2 receptor antagonist (IL-2RA)
Maintenance with steroid + CNI + antiproliferative
Rejection as non HIV patients
Post-transplant prophylaxis
PCP – life long
CMV – as non HIV
MAC: CD count < 50 and stop if > 100
Toxoplasma: IgG+ve recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor positive receive lifelong prophylaxis
Monitor HIV RNA and CD4 count post transplant
Choice of living versus deceased donor
HIV +ve not suitable for live donation
Use of HIV-infected donors for HIV-infected recipients when donor CD4 count > 200 and viral load < 50 in the past 6M with no hx of virological resistance or failure
I appreciate your clinical approach.
Introduction:
In 2013 108,000 people were living with HIV in the UK.
The use of combination antiretroviral therapy (cART) has led to a dramatic reduction in opportunistic infections and death, and to be provided to patients with CD4 cell counts of less than 350 cells/µL, with 87% of those on cART achieved viral suppression.
Immunodeficiency is an important risk factor for chronic kidney disease (CKD) and end-stage kidney disease (ESRD) (6,7), and for liver disease progression in HCV-co-infected patients (8).
HIVAN is the most common cause of end stage renal disease in HIV patients, usually black, young /,36 years with a low CD4 < 66 copies/ml.
Kidney transplantation in the era of c-ART is associated with good overall outcome in HIV patients in the term of graft survival and infectious complications, but some increased risk of rejection reaching 36%.
Indications of kidney transplant of HIV patients:
· All potential kidney transplant recipients are screened for HIV infection (1D).
· HIV per se is not a contraindication for kidney transplantation (1B).
· HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D).
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B).
c) HIV RNA has been undetectable during the previous 6 months (1B) d) No opportunistic infections have occurred during the previous 6 months (1B).
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B).
· The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded).
Indications for pancreas transplantation:
· Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded).
· Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D) • Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded).
Contraindications to transplantation:
The absolute contraindications to kidney transplantation in patients with HIV are:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C).
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D).
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D).
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D).
e) Serious ongoing or recurring infection, including documented history of PML (1D).
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D).
g) Pregnancy (1D)
Progressive multifocal leukoencephalopathy (PML), is a rare and fatal viral disease caused by a polyomavirus and occurs almost exclusively in people with severe immune deficiency, with no cure.
Recommendations and advice may be obtained from the Israel Penn International Transplant Tumor Registry:
· Consultation with an oncologist is required in most cases. In general, a two to five year waiting period is recommended after curative therapy for malignancy, and depends on the followings – (1) the estimated risk of recurrence,(2) extent of disease at the time of treatment,(3) type and grade of tumour, and(4) the treatment given.
· Cardiovascular evaluation is mandatory.
· Patients with advanced cardiopulmonary disease should be excluded.
· Candidates with chronic hepatitis B or C or persistently abnormal liver function testing must have a hepatology evaluation prior to transplantation. Hepatitis B or C infection may be a contraindication to kidney transplantation, especially if there is evidence of active hepatitis or cirrhosis.
· Patients with quiescent disease and a benign liver biopsy can proceed to kidney transplantation, although treatment may be required in some.
· Recipients with a body mass index over 35 kg/m2 are at increased risk of complications after kidney transplantation, including surgical complications, longer length of stay, increased mortality, and higher risk of post transplant diabetes mellitus.
· The human T-cell leukaemia virus (HTLV) is a risk factor for the development of leukaemia and myelopathy after transplantation, persons with HTLV must be informed of this 35 risk before surgery.
· A remote history of treated tuberculosis does not contraindicate transplantation. In cases where the history suggests that there may be a persistent subclinical tuberculosis infection, a consultation with an infectious disease expert may assist in the decision to treat the recipient for tuberculosis, and whether it can be done before or after the transplant.
The relative contraindications to kidney transplantation in HIV patients are:
a) Positive flow cytometric crossmatch (FCXM) (1D).
b) Blood-type incompatibility (2D).
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C).
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D).
e) Chronic liver disease (2D).
f) Marked obesity (BMI >35 kg/m2 ) (2D).
g) HTLV infection (1D).
Assessment of HIV patients pre-transplant:
· All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D).
· Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C).
· Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D).
· Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C).
· Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C).
· Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C).
· Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C).
· All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C).
· All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B).
· Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to .
transplantation (1D).
Solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C).
· Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded).
· Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D).
· Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D).
· Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D).
Against transplantation:
· Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C).
· Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma (1D)
Pancreas-specific assessment:
Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C).
Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded).
Pancreas transplantation assessment in patients with HIV includes:
a) Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy).
b) Vascular assessment (ultrasound assessment of leg vessels, and consider noncontrast CT of aorta and iliac arteries).
c) Consideration of a more extensive cardiac assessment (2C).
Pre-transplant immunisation:
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres 200 cells/µL (1C).
Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B).
Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D) • Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D).
Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV (2C).
Consideration of drug-drug interactions:
Continuation of antiretroviral therapy in the perioperative period following transplantation (1D).
A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded).
A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D).
Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D).
The clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded).
Induction and maintenance immunosuppression recommendations:
· All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C).
· For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B).
· HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C).
· Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D).
Post-transplant prophylaxis recommendations:
· HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D).
· Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A).
· CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A).
· Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C).
· Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C).
· Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C).
· Toxoplasma IgG seropositive recipients with a CD4+ count 100 cells/µL for 6 months (2D)
Monitoring allograft function:
· Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded).
· Local practice for monitoring of the pancreas allograft is followed (Not graded) Monitoring of HIV virological control
· Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B).
· If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D).
· More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D).
Choice of living versus deceased donor:
Consent and confidentiality:
Use of HIV-infected donors for HIV-infected recipients:
a) HIV viral load 200/µL for at least 6 months prior to brain injury.
b) Information about the donor virus such as historical genotype patterns where possible and current viral load.
c) No history of virological failure or drug resistance (1D).
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
EXECUTIVE SUMMARY OF RECOMMENDATIONS
Indications for Kidney transplantation
We recommend that:
HIV-positive patients are wait-listed only if:
We suggest that:
—————————————————————————————————————–
Indications for Pancreas Transplantation
We recommend that:
We suggest that:
——————————————————————————————————————
Contraindications to transplantation
We recommend that:
We suggest that:
——————————————————————————————————————
General assessment
We recommend that:
HIV-specific assessment
We recommend that:
We recommend against:
We suggest that:
——————————————————————————————————————-
Pancreas-specific assessment
We recommend that:
We suggest that:
——————————————————————————————————————-
Pre-transplant immunisation
We recommend that:
We suggest that:
——————————————————————————————————————-
Consideration of drug-drug interactions
——————————————————————————————————————
Induction and maintenance immunosuppression
——————————————————————————————————————-
Post-transplant prophylaxis
Monitoring allograft function
——————————————————————————————————————-
Choice of living versus deceased donor
Consent and confidentiality
——————————————————————————————————————-
USE OF HIV-INFECTED DONORS FOR HIV-INFECTED RECIPIENTS
Recommendations:
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that medical and social information about the recipient is not disclosed,
KIDNEY AND PANCREAS TRANSPLANTATION IN PTS WITH HIV – BTS GUIDELINES.
Indications for kidney transplantation.
Indications for pancreas transplantation.
Contraindication to transplantation.
HIV Specific assessment.
Pancreas specific tx.
Pre transplant immunization
Consideration of DDI.
Induction and maintenance immunosuppression.
Post transplant prophylaxis.
Monitoring allograft function.
Monitoring of HIV virological control.
Choice of living vs deceased donor.
Consent and confidentiality.
Use of HIV infected donor for HIV infected recipients.
Centers with experience in transplanting HIV +VE pts should be allowed to take the lead in handling these pts.
I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Agreed Prof.
Ø Aim of the guidelines:
HAART use decreased the mortality from HIV infection. Interest in transplantation in patients with HIV has increased. these guidelines focus on HIV-infected kidney & pancreas transplantation.
Ø Summary of recommendations:
Indications for Kidney transplantation
recommend that:
• All potential kidney transplant recipients are screened for HIV infection (1D)
• HIV per se is not a contraindication for kidney transplantation (1B)
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been
stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that:
• The most appropriate anti-retroviral therapy is determined before transplantation in
conjunction with an HIV specialist in order to anticipate potential drug interactions and
appropriate dosing of medication (Not graded)
pancreas transplantation:
suggest that:
• Diabetic patients in renal failure and with controlled HIV infection are considered for
simultaneous kidney and pancreas transplantation (2D)
• Diabetic patients with severe hypoglycaemic unawareness may be considered for
solitary pancreas or islet transplantation if they have well controlled HIV and kidney
function that is stable and preserved (eGFR >40mL/min) (Not graded)
absolute contraindications for transplantation in HIV patients:
1- Uncontrolled HIV infection( CD4 T-cell count >100 last 6 months or persistent detection of HIV RNA during last 3 months
2- incompliance to HAART therapy due to psychiatric issues drug abuse
3- Multi drug-resistant HIV infection
4- Positive CDC cross match
5- Active or disseminated malignancy
6- Serious active infection including hx of PML
7- Pregnancy
Relative C/I :
1- Positive FCXM
2- ABO incompatibility
3- Treated malignancy including extracutaneous Kaposi sarcoma
4- CLD
5- Severe uncontrolled medical illness that will not improve with transplantation
6- Marked obesity, BMI >35
7- HTLV infection
Pre-transplant immunization :
– HBV vaccine to all non-immunized ( HBV SAb<10 )
– HAV vaccine to all non-immne patients
– Pneumococcal polysaccharide vaccine 23 to all patients
– Varicella zoster vaccine to all non-immune patients with CD4 cell count >200.
– Influenza vaccine annually to all patients in the waiting list.
– DTP suggested being given to all patients
– MMR vaccine suggested being given to all non-immune to measles
– HPV vaccine is recommended to all at risk of HPV acquisition.
Consideration to drug-drug interaction:
– Recommend continuing HAART perioperatively
– Suggest that pre-imperative switching away from protease inhibitors-based therapy, if alternatives exist, to minimize the interaction.
– Refer to Liverpool HIV drug interaction resource.
Induction & maintenance immunosuppression :
– Use of interleukin -2 receptor antagonist for induction in most of the HIV-positive patients.
– For maintenance, use of triple steroid+CNIs+antiproliferatives
– Acute rejection treated as in HIV-negative patients.
Post transplant prophylaxis:
– Lifelong prophylaxis against pneumococcal pneumonia.
– Prophylaxis against CMV for 3 months in CMV – ve recipients from CMV +ve donors.
– Assessment of latent TB infection & disease if not done before transplantation
– Life-long prophylaxis against toxoplasma, if ig G positive with CD4 <200 or recipient from donor seropositive toxoplasmosis/
– Prophylaxis of mycobacterium avium complex if cd4<50 & stop if cd4>100 for 6 months
Monitoring of HIV virological control:
– HIV RNA & CD4 count after one month, then every 2-3 months for the 1st year, then every 3-6 months thereafter. ( could be done more frequently if the use of lymphocyte-depleting agents)
– If persistent HIV viremia exists, drug resistance testing is carried out.
Living vs deceased donors:
– Same access to living donor kidney transplantation as non-infected patients
– HIV infected are not suitable to be living kidney Donors.
Consent & Confidentiality:
– Standard consent as the same for any other transplant.
– the recipient is encouraged to disclose their diagnosis of HIV to their donor
– All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV
Use of HIV-infected donors for HIV-infected recipients:
– Restricted to deceased donors with 1- HIV viral load <50 persistently for 6 months prior to brain injury
2- no hx of virological failure or drug resistance
– Recipients should be counselled & consented with all information.
I appreciate your clinical approach.
1.Kidney & Pancreas Transplantation in Patients with HIV
Please summarise this article
Introduction
The mortality rate of HIV patients deceased recently when introduced HAART in 1996.but morbidity is increased which is related to chronic conditions related to kidneys,liver , heart.
HIV patients are risky for chronic kidney disease ,ESRD and hemodialysis there for the transplantation is increased .
Indications for Kidney transplantation
Waiting list for kidney transplantation
1.They are concordant with treatment, particularly cART therapy (1D)
2. Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
3.HIV RNA has been undetectable during the previous 6 months (1B)
4. No opportunistic infections have occurred during the previous 6 months (1B)
5.They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Suggestion
The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
Indications for Pancreas Transplantation
Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded)
Suggestion
Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded)
Contraindications to transplantation
absolute contraindications:
1.Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
2.psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
3.Multi-drug resistant HIV infection that cannot be controlled with currently available anti retroviral therapy (ART) (1D)
4. Positive complement-dependent cytotoxic (CDC) crossmatch (1D) e) Serious ongoing or recurring infection, including documented history of PML (1D)
5. Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D) 6.Pregnancy (1D).
relative contraindications to kidney transplantation
1. Positive flow cytometric crossmatch (FCXM) (1D)
2. Blood-type incompatibility (2D)
3. Treated malignancy, including extra cutaneous Kaposi sarcoma (2C)
4. Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
5. Chronic liver disease (2D)
6. Marked obesity (BMI >35 kg/m2) (2D) g) HTLV infection (1D)
HIV-specific assessment
All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
Recommendation against
1.Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
2.Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)related lymphoma (1D)
Suggestion
In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded)
Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D)
Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
Pancreas assessment
Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C) Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded)
The assessment of pancreas transplantation in HIV by:
1.Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy)
2. Vascular assessment (ultrasound assessment of leg vessels, and consider noncontrast CT of aorta and iliac arteries)
3.Consideration of a more extensive cardiac assessment (2C)
The immunization pre transplantation by :
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
Suggestion in immunization
Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D)
Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
drug-drug interactions
Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
Suggestion for drug –drug interactions
• A full and current medication review as part of the assessment for solid organ transplantation, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant (2D)
Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (Not graded)
Induction and maintenance immunosuppression
All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C).
Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C)
Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
Monitoring allograft function
Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
Local practice for monitoring of the pancreas allograft is followed (Not graded)
Monitoring of HIV virological control
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living versus deceased donor
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
Patients with HIV infection are unsuitable to be living kidney donors (1D)
Consent and confidentiality
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded) All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
HIV-infected donors for HIV-infected recipients
Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with: a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury Information about the donor virus such as historical genotype patterns where possible and current viral load .
No history of virological failure or drug resistance (1D)
Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
Patients with HIV-infection are unsuitable to be living kidney donors (1D)
HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
1- BTS Guidelines for renal transplantation in HIV patient:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been
stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma.
Absolute:
1- Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during
the last 6 months and HIV RNA persistently detectable during the last 3 months.
2- Habitual and irremediable non-concordance.
3- Multi-drug resistant HIV infection.
4- Positive CDC cross match.
5- serious onging or recurrent infection including PML
6- Active Malignancy
7- pregnancy.
Relative:
1- Positive FCXM
2- ABO incompatibility
3- Treated malignancy including extra-cutaneous Kaposi.
4- severe or uncontrolled medical condition
5- chronic liver disease
6- Obesity (BMI>35)
7- HTLV infection
• All transplant candidates undergo careful immuno-virological and antiretroviral status
review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral
therapies, HLA-B5701 status and HIV resistance profile.
• Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid
organ transplantation if otherwise well and fully adherent with their medications.
• Transplant candidates undergo screning:
-liver cirrhosis or active HCV infection.
-history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary
effusion lymphoma or Epstein-Barr virus (EBV)-elated lymphoma
Recommended vaccination:
Suggested vaccines:
1- HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to
brain injury
2- Information about the donor virus such as historical genotype patterns where
possible and current viral load
3- No history of virological failure or drug resistance.
I appreciate your clinical approach.
Introduction
o This is a BTS guidelines (Kidney & Pancreas Transplantation in Patients with HIV), March 2015 [Minor Revision January 2017]
o UK guidelines recommend that combination antiretroviral therapy (cART) be provided to all patients with CD4 cell counts of <350 cells/µL (87% achieved viral suppression)
o With current cART, we can expect a near-normal life expectancy
o HIV-associated nephropathy (HIVAN) is the commonest cause of ESRD in HIV-positive patients in the UK
o HIV infection is not associated with an increased risk of diabetes mellitus per se but drugs (indinavir, lopinavir/ritonavir, stavudine, zidovudine and didanosine) may be associated with greater disturbances of glucose homeostasis
HIVAN:
o Black are at increased risk
o Typically young (mean age 36 years)
o With severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median eGFR] 21 mL/min/1.73m2) at diagnosis
o Majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
Indications of kidney transplantation
o In carefully selected HIV-positive patients, patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation
o Some studies report a high acute rejection rates (is >50%). The explanation is unclear, although immunological, pharmacological, and racial factors seem to have a role
o The most appropriate anti-retroviral therapy for an individual patient should be discussed with the HIV/infectious disease team before transplantation
o Integrase inhibitors do not inhibit the P-450 (limited experience of the use in patients with ESKD, and, reduced absorption if co-prescribed with phosphate binders)
Recommendation states
We recommend that all potential kidney transplant recipients are screened for HIV infection (1D)
We recommend that HIV per se is not a contraindication for kidney transplantation (1B)
We recommend that HIV-positive patients are wait-listed only if:
1. They are concordant with treatment, particularly cART therapy (1D)
2. Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
3. HIV RNA has been undetectable during the previous 6 months (1B)
4. No opportunistic infections have occurred during the previous 6 months (1B)
5. They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
We suggest that the most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication (Not graded)
Indications of pancreas transplantation
Recommendation states
We recommend that potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and also in solitary pancreas or islet transplantation (Not graded)
We suggest that diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation (2D)
We suggest that diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved (eGFR >40mL/min) (Not graded)
Contraindications to transplantation
Infections considered contraindications to transplantation:
1. Deep and persistent infections or infections with resistant bacteria and fungi [empyema, Aspergillus infection and colonization, infection with other invasive fungi, and infection with Methicillin-resistant Staphylococcus aureus (MRSA) or Vancomycin-resistant Enterococcus (VRE)]
2. Untreated active chronic infections (active CMV and mycobacterial infection, unless there is clear evidence of successful treatment)
3. Progressive multifocal leukoencephalopathy (PML), which is a rare and usually fatal viral disease caused by a polyomavirus and occurs almost exclusively in people with severe immune deficiency
4. Self-limiting infections within the last 30 days where there is a significant risk of reactivation with immunosuppressive therapy [influenza or respiratory syncytial virus (RSV)]
Recommendation states
We recommend that the following are absolute contraindications to kidney transplantation in patients with HIV
1. Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
2. Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
3. Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
4. Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
5. Serious ongoing or recurring infection, including documented history of PML (1D)
6. Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
7. Pregnancy (1D)
We suggest that the following are relative contraindications to kidney transplantation
1. Positive flow cytometric crossmatch (FCXM) (1D)
2. Blood-type incompatibility (2D)
3. Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
4. Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
5. Chronic liver disease (2D)
6. Marked obesity (BMI >35 kg/m2) (2D) g) HTLV infection (1D)
General assessment
Recommendation states
We recommend that existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded)
HIV-specific assessment
Additional objectives from an HIV perspective:
1. To ensure infectious complications post-transplantation are minimised through screening, immunisation and/or the provision of treatment
2. To formulate a management plan that allows the safe co-administration of combination antiretroviral therapy (cART) and immunosuppression
o The appropriate cART regimen for patients awaiting SOT is determined by the presence of HIV resistance mutations and the recipient’s ability to tolerate specific antiretrovirals
o Thymidine analogues (stavudine and zidovudine) and didanosine should be avoided
o Non-nucleoside reverse transcriptase and integrase inhibitors have a minimal or no drug-drug interactions with immunosuppressants
o Ritonavir- (or cobicistat-) boosted protease or integrase inhibitors require careful adjustment of especially calcineurin-inhibitors
o Tenofovir disoproxil fumarate and atazanavir are associated with kidney injury and kidney disease progression (should be avoided)
Recommendation states
We recommend that all transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile (1D)
We recommend that patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications (1C)
We recommend that transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii (1D)
We recommend that transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines (1C)
We recommend that transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease (1C)
We recommend that transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation (1C)
We recommend that transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation (1C)
We recommend that all transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
We recommend that all hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed (1B)
We recommend that patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation (1D)
We recommend against:
1. Kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
2. SOT in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)related lymphoma (1D)
We suggest that
o In selected cases, solid organ transplantation may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
o Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided in the setting of kidney transplantation if suitable alternatives are available (Not graded)
o Antiretrovirals with significant drug-drug interactions with calcineurin inhibitors (ritonavir and cobicistat) are avoided in the setting of solid organ transplantation if suitable alternatives are available (2D)
o Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation (2D)
o Anti-HBc positive “alone” recipients (donor negative, recipient sAg and DNA negative) do not require routine antiviral prophylaxis against HBV reactivation, but this may be considered in those felt to be at increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
Pancreas-specific assessment
Recommendation states
We recommend that:
o Assessment of such potential transplant recipients is performed in a centre that regularly performs renal transplantation in HIV patients and that also regularly performs pancreas transplantation (1C)
o Transplant candidates are carefully counselled and informed that there is currently relatively little experience of pancreas transplantation performed in HIV-infected patients (Not graded)
We suggest that:
o Pancreas transplantation assessment in patients with HIV includes: a) Diabetic assessment (for hypoglycaemic unawareness, peripheral neuropathy, & autonomic neuropathy)
o Vascular assessment (ultrasound assessment of leg vessels, and consider noncontrast CT of aorta and iliac arteries) c) Consideration of a more extensive cardiac assessment (2C)
Pre-transplant immunization
Recommendation states
We recommend that:
o Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL) (1B)
o Hepatitis A virus (HAV) vaccine is administered to all non-immune patients (1D)
o Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients (1B)
o Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL (1C)
o Influenza vaccine is administered annually to patients awaiting solid organ transplantation (1B)
We suggest that:
o Diphtheria, tetanus and pertussis (DTP) vaccine is administered to all patients (2D)
o Measles, mumps and rubella (MMR) vaccine is administered to all patients who are nonimmune to measles (2D)
o Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV acquisition (2C)
Consideration of drug-drug interactions
Recommendation states
We recommend:
o Continuation of antiretroviral therapy in the perioperative period following transplantation (1D)
We suggest:
o A full and current medication review as part of the assessment for sot, to be repeated at least twice yearly thereafter, and at every key therapeutic decision point (Not graded)
o A dose-finding trial of calcineurin-inhibitors prior to SOT in order to determine optimum doses to initiate post-transplant (2D)
o Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions (2D)
o That all clinical correspondence carries a footer referring practitioners to the Liverpool HIV Drug Interactions Resource (www.hiv-druginteractions.org) (Not graded)
Induction and maintenance immunosuppression
Recommendation states
We recommend that:
o All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation (1C)
o For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
o HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent (1C)
We suggest that:
o Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
Recommendation state
We recommend that:
o HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation (1D)
o Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months (1A)
o CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months (1A)
o Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation (1C)
o Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis (1C)
o Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing (1C)
We suggest that:
o Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis (2C)
o Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected (2D)
o Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
Monitoring allograft function
Recommendation states
We recommend that:
o Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
We suggest that:
o Local practice for monitoring of the pancreas allograft is followed (Not graded)
Monitoring of HIV virological control
Recommendation states
We recommend that:
o Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter (1B)
o If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options (1D)
We suggest that:
o More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis (2D)
Choice of living versus deceased donor
Recommendation states
We recommend that:
o Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
o Patients with HIV infection are unsuitable to be living kidney donors (1D)
We suggest that:
o Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality
Recommendation states
We recommend that:
o Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
o The standard of consent for HIV-positive transplant candidates is the same as for any other transplant (Not graded)
o Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance (Not graded)
We suggest that:
o Wherever possible, the recipient is encouraged to disclose their diagnosis of HIV to their donor (Not graded)
o All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
o All living donors are made aware that there may be medical and social information about the recipient that is not disclosed (Not graded)
o All living donors are asked to acknowledge that they are aware that they will not be given confidential information about the recipient which is not deemed relevant to the outcome of the kidney transplant (Not graded)
Use of HIV-infected donors for HIV-infected recipients
Recommendation states
We recommend that:
o Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
b) b) Information about the donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance (1D)
o Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
o Patients with HIV-infection are unsuitable to be living kidney donors (1D)
We suggest that:
o HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
BTS Kidney and Pancreas Transplantation in Patients with HIV
Summary of the Article
Indications for kidney transplantation
We recommend that
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell count is > 100 cells/microL (ideally > 200 cells/microL) and has been stable the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
We suggest
Indications for Pancreas Transplantation
We recommend that
We suggest that
Contraindications to transplantation
We recommend that
a) Uncontrolled HIV infection (CD4+ T cell levels persistently < 100 cells/microL during the last 6 months and HIV RNA persistently detectable during the previous 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems, or persistent substance abuse (1D)
c) Multi-drug resistance HIV infection that can not be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic crossmatch (1D)
e) Serious ongoing or recurring infection, including a documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
HIV specific assessment
We recommend
We recommend against
We suggest that
Pancreas-specific assessment
We recommend that
We suggest that
a) Diabetic assessment (hypoglycemia unawareness, peripheral neuropathy, and autonomic neuropathy)
b) Vascular assessment (US leg vessels, and contrast CT of the aorta and iliac arteries.
c) Consideration of extensive cardiac assessment (2C)
Pre-transplant immunisation
We recommend that
We suggest that
Consideration of drug-drug interactions
We recommend
We suggest
Induction and maintenance immunosuppression
We recommend that
We suggest that
Post Tx prophylaxis
We recommend that
We suggest that
Monitor allograft function
We recommend that
Monitor HIV virological control
We recommend that
We suggest that
Choice of living vs deceased donor
We recommend that
We suggest
Consent and confidentiality
We recommend that
We suggest that
Use of HIV-infection donors for HIV-infected recipients
We recommend that
a) HIV viral load <50 copies and CD4 count >200 for at least 6 months prior to brain injury.
b) Information about the donor virus such as historical genotype patterns where possible and current viral load.
c) No history of virological failure or drug resistance (1D)
We suggest that
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Thank you prof.
Summarize this article I
Recommendations & suggestions:
Indications for kidney transplantation
Recommendations:
· Screening for HIV is mandatory for all recipients (1D)
· HIV is not a contraindication for kidney transplantation
· HIV-positive patient is considered for transplantation when they are compliant with Cart treatment (1D), stable CD4 count > 100 over the last 3 months (1B), undetectable viral load & absence of opportunistic infections over the last 6 months, Absence of lymphoma.
Suggestions
· HIV specialist should be involved in the management before proceeding to transplantation
Indication for pancreas Transplantation
Recommendation
· HIV positive recipient should be evaluated in a center with experience in transplanting HIV positive patients
Suggestions
· Consider simultaneous kidney and pancreatic transplantation in diabetic, HIV and ESKD (2D)
· Severe hypoglycemic unawareness in diabetic, HIV, and stable CKD (eGFR > 40 ml/min) can be listed for either solitary pancreas or islet cell transplantation (not graded)
General assessment
· This should follow the same guideline for non-HIV recipients (not graded)
HIV-specific assessment
Recommendations
· Check CD4 count, viral load, HLA-b5701, & HIV resistance profile (1D)
· Tests for syphilis, HSV, EBV, CMV, VZT, Toxoplasma gondii (1D)
· Evaluate for latent TB by IGRA and rule out active TB in those with positive results (1D)
· Treat latent or active TB according to NICE guidelines before proceeding to transplantation
· Screening for viral hepatitis is mandatory (1C)
· Those who are discovered to have HBV should treated before transplantation to the point of viral suppression (1B). liver cirrhosis is a contraindication for transplantation (1B) as well as active HCV infection (1C)
· Screening for anogenital cancer should be carried out for all candidates (1D)
Suggestions
· Transplantation may be considered in special situation when the patient is virally suppressed & CD4 count is < 200 but > 100 cells/microliter (2C)
· Avoid ARVs such as TDF and atazanavir if possible due to potential risk of nephrotoxicity (not graded)
· Avoid ARVs with significant drug -drug interactions with CNIs (ritonavir & cobicistat) whenever possible (2D)
· Screening for strongyloides steroralis in endemic areas before transplantation (2D)
· Recipient with only anti-HBc Ab is low risk and may not requires antiviral prophylaxis unless they had received lymphodepleting induction therapy
Pancreas-specific assessment
Recommendation
· All recipients should be evaluated in center with experience in HIV & pancreatic transplantation (1C)
· Patients must be informed & educated that, the experience in these areas is very limited (not graded)
Suggestions
· Consider diabetic (hypoglycemia unawareness, neuropathy), vascular (e.g., PVD, non-contrast CT of the aorta & iliac vessels), & cardiac assessments
Pre-transplant immunization
Recommendations
1. HBV vaccine for those with HBVsAb < 10 mIU/ml (1B)
2. HAV vaccine (1D)
3. Pneumococcal polysaccharide vaccine (PPV-23) (1B)
4. VZV vaccine (1C)
5. Annual influenza vaccine (1B)
Suggestions
1. DTP vaccine (2D)
2. MMR vaccine (2D)
3. HPV (2C)
Consideration for drug-drug interactions
Recommendation
· Continue ARVs (1D)
Suggestions
· Review treatment at least twice yearly (not graded)
· Try to find the optimal dose of CNIs by giving the drug before transplantation (2D)
· Reduce drug -drug interaction by avoiding boosted Pi ARVs whenever possible (2D)
Induction & maintenance immune suppression
Recommendations
· Induction treatment is to be given to all HIV patients (1C)
· IL-2RA is the standard for most HIV patients (1B)
· Triple immune suppression for maintenance is not different from non-HIV population (1C)
Suggestions
· Treatment of rejection is similar to non-HIV population (2D)
Posttransplant prophylaxis
Recommendations
· Prophylaxis against PCP is for life (1D)
· CMV prophylaxis is not different from the general population (1A)
· Evaluate for LTB or active TB before transplantation (1C)
· Re-evaluate should be done for those who are re-exposed to TB after transplantation according to NICE guideline (1C)
Suggestions
· Toxoplasma IgG positive recipients with CD4 < 100 or any recipient of toxoplasma positive donor organ should be given prophylaxis for life time (2C)
· Prophylaxis against MAC is indicated when CD4 is < 50 and to be stop when CD4 is > 100 for at least 6 months (2D)
Monitoring of allograft function
Recommendations
· Follow the same guidelines for the general population (not graded)
Suggestions
· Follow practice guidelines for pancreas allograft (not graded)
Monitoring of HIV virus control
Recommendations
· HIV PCR should be done 1 month after transplantation then every 2 to 3 months for the first year & 3 to 6 months after the first year (1B)
· Order HIV-drug resistance profile in cases of HIV viraemia (1D)
Suggestions
· Consider CD4 monitoring for patient who received lymphodepleting agents (2D)
Choice of living versus deceased donor
Recommendations
· Access to living donor kidney transplantation should be the same as the general population (1B)
· HIV infected person is suitable as a living donor (1D)
Suggestion
· Donors may be informed the potential risk for the recipients but the disclosure of the HIV status is not mandatory (not graded)
Consent and confidentiality
Recommendations
· Follow the same ethical guidelines for the non-HIV individuals (not graded)
Suggestions
· The recipients may be encouraged to disclose their status to their donors if that is possible (not graded)
· Donors should be in told that, the medical & social information of their recipients are confidential (not graded)
Use of HIV-infected donors for HIV-infected recipients
Recommendations
· This is only in deceased donor set up and the donor must fulfil the following criteria: 1. HIV viral load < 50, and CD4 > 200 for at least 6 months before brain death, 2. Information about the virus is available, 3. No history of drug resistance (1D)
· The recipient must be counselled at the time of enlisting and at the time of transplantation (1D)
· HIV positive person is not suitable as a living donor (1D)
Suggestions
· Transplantation of HIV positive organs should be left for centers which have the experience for HIV positive transplantation (not graded)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated. I appreciate your emphasis on ‘equity of distribution’ of donor organs irrespective of prospective recipient’s HIV status.
Thanks prof
SUMMARY
Introduction
The introduction of HAART medication in 1996 has reduced the incidence of morbidity and mortality associated with HIV disease. However, as these medications are prolonging their life, it is also giving rise to diseases associated with aging of which CKD take a dominant role among patient living with HIV. Moreover, because of increased cardiovascular risk among those using dialysis as a form of renal replacement therapy, there has been a growing interest in kidney transplantation among patients with HIV.
In light of this, BTS has made the following recommendation for the optimal outcome for HIV patients undergoing kidney transplantation.
Indication for kidney transplantation
a) They are concordant with treatment, particularly cART therapy
b) CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of PML, intestinal cryptosporidiosis, or lymphoma.
Absolute contraindication to kidney transplant
Relative contraindication to kidney transplantation
HIV specific assessment
Induction and maintenance of immunosuppression
Post- transplant prophylaxis
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays 1 month after transplant and subsequent studies every 2-3 months for the first year and then every 3-6 months subsequently.
Living versus diseased donor
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients. Patients with HIV infection are unsuitable to be living kidney donors (1D)
Use of HIV-infected donors for HIV-infected recipients
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney and Pancreas Transplantation in Patients with HIV (Second edition, March 2015)
HIV-positive patients are wait-listed if:
Absolute contraindications for kidney transplantation in HIV-positive patients
HIV-specific assessment
cART suggestion
Vaccination pre-transplantation
Post-transplant prophylaxis
I understand your suggestion about immunisation of prospective recipients.
Kidney & Pancreas Transplantation in Patients with HIV, BTS, second edition 2015
Indications for Kidney transplantation:
Screen all KTR for HIV infection (1D)
HIV is not a contraindication for KTx (1B)
HIV-positive patients are wait-listed only if:
a) Commenced on cART therapy and adherent with treatment (1D)
b) Stable CD4+ T count in the past 3 months >100 cells/μL (ideally > 200 cells/ μL) (1B)
c) Undetectable HIV RNA in last 6 months (1B)
d) No opportunistic infections in last 6 months (1B)
e) No previous PML, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Suggestions:
cART to be discussed and determined before KT (Not graded)
Indications for Pancreas Transplantation:
Recommend that diabetic HIV patients with controlled infection and in renal failure are candidates for simultaneous kidney and pancreas transplantation (2D).
Recommend that diabetic HIV patients may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and their kidney function is stable at eGFR >40mL/min.
If they have severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if kidney function is stable. (Not graded)
Pancreas recipients should be assessed in center expert in KT for HIV-positive patients, and in pancreas or islet transplantation (Not graded)
Absolute Contraindications to transplantation:
a) Uncontrolled HIV infection; persistently CD4+ <100 cells/μL in last 6 m and persistent HIV RNA detectable in last 3 months (1C)
b) Habitual and irremediable non-concordance with treatment due to major psychiatric disease or persistent substance abuse. (1D)
c) multi-drug resistant HIV infection. (1D)
d) Positive CDC crossmatch (1D)
e) Serious ongoing or recurring infection PML (1D)
f) Malignancy (active or disseminated) (1D)
g) Pregnancy (1D)
Relative contraindications to kidney transplantation:
a) Positive FCXM (1D)
b) ABOi (2D)
c) Treated malignancy; including Kaposi sarcoma (2C)
d) Uncontrolled medical problems (2D)
e) Sever Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
General assessment:
Recommended to follow existing guidelines for all candidate with HIV disease (Not graded)
HIV-specific assessment:
Should performed in experience center with HIV patients.
Evaluate virological and cART status; CD4 cell count, HIV RNA level, resistance profile and cART history (1D)
If HIV RNA <200 copies/mL, considered Tx if fully adherent with medications (1C)
Serology for syphilis, HSV, EBV, CMV, VZV, HTCLV, Toxoplasma gondii & Strongyloides stercoralis (1D)
TB screening & treatment prior to Tx (active and LTBI); with IGRA +/- TST (1C)
Screened for viral hepatitis; If serology positive to confirm with NAT and to look for cirrhosis (1C)
HBsAg positive patients to receive treatment and ensure viral suppression (1B)
Screen & treat for cervical and/or anal neoplasia (1D)
SOT can be considered if HIV RNA suppressed & CD4 < 200 but >100 cells/μL (2C)
Avoid antiretrovirals with nephrotoxic potential or drug-drug interactions.
Anti-HBc positive “alone” recipients do not require prophylaxis unless reactivation risk is high.
Pre-transplant immunization:
HBV vaccine to all patients if HBVsAb <10 mIU/mL (1B)
HAV vaccine (for non-immune) (1D)
PPV-23 (1B)
VZV vaccine (non-immune) with CD4 >200 cells/μL (1C)
Influenza vaccine annually (1B)
DTP to all patients (2D)
MMR (nonimmune) (2D)
HPV for high risk (2C)
Consideration of drug-drug interactions:
Recommended to consider cART in the perioperative period (1D)
Medication review as part of the assessment (Not graded)
CNI trials to determine optimum doses (2D)
Switching from PI regimens to minimize drug interactions (2D)
Induction and maintenance immunosuppression:
Induction therapy offered to All KTR with HIV-positive at time of Tx1C)
Induction therapy is with IL-2RA (1B)
Triple maintenance IS started at the time of kidney transplantation
Acute rejection is treated the same way as HIV-negative KTR (2D)
Post-Transplant Prophylaxis:
lifelong prophylaxis against PCP (1D)
CMV prophylaxis; if CMV R-/ D+ for of 3 months (1A)
Recipient CMV positive; either prophylaxis or surveillance and pre-emptive therapy for 3 mo(1A)
Assess and treat LTBI prior to transplantation, revaluate if new exposure history or symptoms develop, and treat as per NICE guidelines (1C)
Toxoplasma lifelong prophylaxis if either donor is positive or recipient positive & CD4 <200 (2C)
MAC prophylaxis; if CD4 count ≤ 50. To be stopped when the count is >100 cells/μL for 6
months (2D)
Monitoring allograft function:
Follow the current guidelines for post-operative care of the KTR (Not graded)
Monitoring virological control:
Post-Tx regular measurement of: HIV RNA and CD4+ T-cell counts, at 1 month then q 2-3 months for the first year then every 3-6 months (1B), more frequent if receiving antibody depleting to assess the need for prophylaxis (2D)
If viremia persistent HIV, test for drug-resistance (1D)
Choice of living versus deceased donor:
Access to living donor KT should be the same as non-infected patients. (1B)
HIV donors are unsuitable for donation (1D)
Disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality:
Follow the current guidelines on the ethics for all donors (Not graded)
Donor consent should be adequate and transparent and established in advance (Not graded)
Encourage the recipient to disclose HIV diagnosis to their donor (Not graded)
Donors are asked about any condition cause them to change their decision to donate, without highlighting HIV (Not graded)
Donors should be aware about that medical and social or confidential information about the recipient that is not disclosed (Not graded)
Use of HIV-infected donors for HIV-infected recipients:
Using HIV-infected organs is restricted to organs from DD with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to
brain injury
b) Genotype patterns where possible and current viral load
c) No virological failure or drug resistance (1D)
Recipients are counselled and give informed consent (1D)
LD with HIV-infection are considered for donation (1D)
The use of HIV+ organ is restricted to experience centers
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney transplantation indications
It is recommended that:
• Possible renal transplant recipients have to be screened for HIV infection
• HIV by itself, is not a contraindication for renal transplantation
• HIV-positive patients are wait-listed only if
v they are applicable to receive c ART
v CD4+ T cell counts >100 cells/µL (best >200 cells/uL) and is stable within the last 3 months
v HIV RNA is undetectable within the last 6 months
v No opportunistic infections detected within the last 6 months
v Cases without progressive multifocal leukoencephalopathy (PML), chronic intestinal cryptosporidiosis, or lymphoma histories
It suggested that the suitable anti-retroviral therapy need to be detected pre transplantation with an HIV specialist consultation to notify possible drug interactions and proper dosing of medications.
Pancreas Transplantation indications
It is recommended that
· Possible HIV positive pancreas transplant recipients need to be evaluated by an experienced centre in kidney transplantation for HIV-positive patients, also in solitary pancreas or islet transplantation.
It is suggested that diabetic patients having renal failure and controlled HIV infection can be assessed for simultaneous kidney and pancreas transplantation .
Also diabetic patients with unrecognition of severe hypoglycaemia , well controlled HIV and stable kidney function can be included for solitary pancreas or islet transplantation .
Transplantation contraindication
In HIV cases ,renal transplantation is absolutely contraindicated if
T HIV infection isn’t under control
T Habitual and untreatable non-concordance
T Multi-drug resistant uncontrolled HIV infection
T Positive CDC crossmatch
T Severe occurring or recurrent infection as PML
T Active malignancy that is treated , metastasizing cancer, disseminated or untreated cancer
T Pregnancy
It was suggested that relative contraindications for kidney transplantation are
ü Positive FCXM
ü ABO incompatibility
ü Treated malignancy
ü Severe uncontrollable medical problems
ü Chronic liver disease
ü Marked obesity
ü HTLV infection
General assessment
It is recommended that current guidelines for assessment, choosing and preparation of the possible recipients are the same as that for recipients with HIV disease.
HIV-specific assessment
It is recommended that
• Transplant candidates need precise immuno-virological and antiretroviral status evaluation as CD4 cell count, HIV RNA level, present and previous antiretroviral treatments, HLA-B5701 status and HIV resistance profile.
· Cases having HIV RNA levels <200 copies/mL can be suitable for transplantation if all other issues are in acceptable range.
• Transplant candidates need serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma .
• Transplant candidates are tested for latent TB infection with
an interferon-gamma test with or without Mantoux test as per the strategy of testing in immunocompromised cases in the current NICE Tuberculosis Guidelines.
· Transplant candidates who are positive for latent TB infection
are evaluated for active TB.
• Those with active TB disease are treated as current NICE guidelines before transplantation
· Transplant candidates with latent TB infection, without active
disease are treated for latent TB infection as per NICE TB guidelines, before transplantation
• All transplant candidates are screened for viral hepatitis. Cases with HBsAg or HCV Ab positive need to undergo testing for HBV DNA and HCV RNA levels and evaluated for liver cirrhosis
· HBs Ag positive patients on waiting list for SOT need to be treated to confirm HBV DNA is cured
· Candidates for SOT are evaluated for the presence of cervical and/or anal neoplasia; cases having advanced cervical/anal intraepithelial neoplasia or carcinoma in situ must be treated before transplantation.
It was advised against
· Kidney and/or pancreas transplantation in cases having liver cirrhosis and in cases having active HCV replication
• SOT in cases with history of Castleman’s disease, (HHV8)-related primary effusion lymphoma or (EBV)-related lymphoma
It is suggested that
· In certain cases, SOT can be suitable for cases with fully
suppressed HIV RNA and a CD4 cell count <200 cells/µL but >100 cells/µL
• Antiretrovirals with nephrotoxic potential are avoided in renal transplantation if proper substitutes are available
· Antiretrovirals with drug-drug interactions with CNI (ritonavir
and cobicistat) are avoided in SOT if proper the setting of solid alternatives are available .
• Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection before transplantation
· HBc Ab positive only recipients (donor negative, recipient sAg and DNA negative) do not need routine antiviral prophylaxis but it can be donein cases with increased risk of reactivation
Pancreas-specific assessment
It is recommend that
· Possible transplant recipients evaluation need to be carried out in a centre that is experienced in renal transplantation in HIV patients and experienced in pancreas transplantation
· Transplant candidates need to be precisely counselled and informed that the present experience of pancreas transplantation in HIV-infected patients is not much.
It is suggested that
• Pancreas transplantation evaluation in HIV cases involves diabetic , vascular and cardiac assessment
Pre-transplant immunisation
It is recommend to
• administer Hepatitis B virus (HBV) vaccine to all non-immune patients (HBV sAb titres <10 mIU/mL)
• administer Hepatitis A virus (HAV) vaccine to all non-immune cases
•administer Pneumococcal polysaccharide vaccine (PPV-23) to all cases
• administer Varicella zoster vaccine (VZV) vaccine to non-immune cases with CD4 cell counts >200 cells/µL
• administer Influenza vaccine to patients on SOT waiting list
It is suggest to
• give DPT to all cases
• give MMR vaccine to all patients nonimmune to measles
• offer HPV vaccine to patients at risk of HPV acquisition
Drug-drug interactions consideration
It is advised to maintain antiretroviral therapy in perioperative period after transplantation.
It is suggested
· for evaluation of SOT to do full medical review and repeat it at least twice yearly afterwards.
· To do CNI dose finding trial before SOT to know the optimum doses started after transplantion
· Preventive avoidance boosted protease-inhibitors (PI)-based antiretroviral regimens, if substitutes ae there exist, to decrease drug interactions
· Liverpool HIV Drug Interactions Resource can be used
Induction and maintenance immunosuppression
It is advised that:
• All HIV-positive patients considered for renal transplantation to be offered induction therapy at transplantation time which is interleukin-2 receptor antagonist for most cases
• HIV-positive cases can take triple immunosuppressive maintenance therapy at kidney transplantation time , including steroids ,CNI and anti-proliferative agent
It is suggested to:
• treat acute rejection in HIV-positive kidney transplant recipients the same as treating HIV-negative kidney transplant recipients
Post-transplant prophylaxis
It is advised to
• administer lifelong prophylaxis against Pneumocystis pneumonia in HIV-positive transplant recipients post transplantation
•give prophylaxis against CMV for CMV seronegative recipients receiving organs from CMV seropositive donors at least for 3 months
• give prophylaxis against CMV infection or do PCR surveillance and pre-emptive treatment for at least 3 months to CMV seropositive transplant recipients
· Transplant recipients asymptomatic and not evaluated and treated for latent or active TB infection have to be assessed before transplantation as per guidelines
· Transplant recipients asymptomatic and evaluated and treated for latent or active TB infection before transplantation donot need reassessment for latent TB expect if there is history of new exposure
· Re-exposure of recipients to tuberculosis post transplantation need evaluation for TB latent infection and/or disease as recommended in NICE TB guidelines
It is suggested that:
• Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL or recipients from a donor seropositive for toxoplasmosis need to receive lifelong prophylaxis.
• When there is dependable previous history of treated TB infection it is unneeded to do more tests also those cases do not need TB prophylaxis except if TB re-exposure is doubted .
• Prophylaxis against Mycobacterium avium complex (MAC) is needed when the CD4+ count is ≤ 50 cells/µL, and it can be terminated when the CD4 count is >100 cells/µL for 6 months
Monitoring allograft function
It is advised to follow current guidelines for post-operative care of the kidney transplant recipient for recipients with HIV disease
It is suggested to follow local practice for monitoring of the pancreas allograft
Monitoring of HIV virological control
It is recommend to
• measure quantitative HIV RNA and CD4+ T-cell counts regularly, starting 1 month after transplant and thereafter every 2-3 months for the first year then every 3-6 months
• For cases with HIV viraemia, drug-resistance testing is needed to determine treatment options.
It is suggested that
• frequent monitoring of CD4 count will be needed in patients receiving depleting antibodies to notice the need for anti-infective prophylaxis
Choice of living versus deceased donor
It is recommend that:
• HIV infected cases should have the same access to living donor kidney transplantation as non-infected patients
• HIV infected cases are unsuitable to be living kidney donors
It is suggested that:
• Possible donors for HIV infected cases have to be informed of medical, surgical, and psychosocial factors that can affect the recipient’s morbidity and mortality risk but disclosing the recipient’s HIV status is not a must
Consent and confidentiality
It is recommend that:
• guidelines on the ethics of deceased donor and living donor transplantation need to be followed for all transplantation including those with HIV disease and the same standard of consent
• Transplant teams must guarantee the adequacy of donor consent and the transparency of procedures in advance
It is suggested that
· the recipient is encouraged to inform their diagnosis of HIV to their donors
· the donor must be asked if there is any medical disease that can let them reject donation without saying it is HIV also donors have to be informed that there is a medical condition the recipient has but is unrevealed
· living donors need to be acknowledged that they are aware that confidential data concerning the recipient won’t be told to them
Use of HIV-infected donors for HIV-infected recipients
It is recommend that:
· Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
-HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months before brain injur
-Information about the donor virus such as historical genotype and viral load
-No history of drug resistance
· Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
· Patients with HIV-infection cannot be living kidney donors
It is suggested that HIV+ organ transplant to be carried out only in centres that have experience in transplanting HIV+ cases
I understand your suggestion about immunization of prospective recipients.
Kidney transplant & HIV infection:
Indications of pancreatic transplant & HIV:
Contraindication for transplantation:
(A) Absolute:
(B) Relative:
Potential recipient assessment:
Pancreatic transplant specific assessment:
Pre-transplant immunization:
Drug interaction:
Induction & maintenance immunosuppression & prophylaxis :
Monitoring of HIV virology control:
Live vs deceased HIV donors:
Consent & confidentiality:
HIV donor to HIV recipients:
I appreciate that it is better to build and concentrate efforts to transplant HIV+ organ restricted to centers with HIV+ transplant patients.
Indications for Kidney transplantation
Contraindications to transplantation
Absolute contraindications
Relative contraindications:
General assessment:
HIV-specific assessment
Recommendation against:
We suggest that:
Pre-transplant immunisation
Consideration of drug-drug interactions
Induction and maintenance immunosuppression
Post-transplant prophylaxis
Monitoring allograft function
Monitoring of HIV virological control
Choice of living versus deceased donor
Consent and confidentiality
Use of HIV-infected donors for HIV-infected recipients
Typing whole sentence in bold or typing in capitals amounts to shouting.
I like your clinical approach and well-structured detailed summary.
Kidney & Pancreas Transplantation in Patients with HIV, BTS, second edition 2015
Indications for Kidney transplantation
· HIV is not a contraindication for kidney transplantation.
HIV-positive patients are wait-listed only if:
· They are adherent with treatment.
· Their CD4+ T cell counts are >100 cells/µL and stable during the previous 3 months.
· Negative HIV RNA level during the previous 6 months.
· No opportunistic infections during the previous 6 months.
· No history of progressive multifocal leukoencephalopathy or lymphoma.
Indications for Pancreas Transplantation
· It is suggested that diabetic HIV patients with controlled infection and in renal failure are candidates for simultaneous kidney and pancreas transplantation.
· It is suggested that diabetic HIV patients may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and their kidney function is stable at eGFR >40mL/min.
Absolute Contraindications to transplantation
· Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months.
· Non-concordance due to major psychiatric disease or persistent substance abuse.
· Multi-drug resistant HIV infection.
· Serious ongoing or recurring infection.
· Active malignancy.
· Positive CDC crossmatch.
· Pregnancy
Relative contraindications to kidney transplantation
· Positive FCXM
· Blood group incompatibility
· Treated malignancy
· Severe chronic liver disease, Marked obesity, HTLV infection
HIV-specific assessment
It is recommended that:
· HIV transplant candidate should have their CD4 cell count and HIV RNA level carefully assessed and monitored.
· They should be tested for syphilis, HSV, EBV, CMV VZV, HTL virus and Toxoplasma gondii.
· Also tested for latent TBI with an IGRA test.
· Transplant candidates with latent TBI, should be treated prior to transplantation.
· All transplant candidates are screened for viral hepatitis. If found to be HBs Ag positive or HCV antibody positive should be assed and treated according to current guideline.
Pre-transplant vaccination include:
· HBV and HAV vaccine
· Pneumococcal polysaccharide vaccine
· VZV vaccine is administered to patients with CD4 cell counts >200 cells/µL
· Influenza vaccine
Induction and maintenance immunosuppression
· All HIV-positive transplant candidate should be offered induction therapy at the time of transplantation with IL-2RA
· HIV-positive patients should be given triple therapy maintenance immunosuppression.
· AR can be treated in the same way as HIV-negative kidney transplant recipients.
Post-transplant prophylaxis
HIV positive patients should receive:
· Lifelong pneumocystis pneumonia prophylaxis.
· CMV prophylaxis is indicated in CMV negative recipients if donor is CMV positive.
· If CMV seropositive transplant recipients should receive either prophylaxis, or PCR observation and pre-emptive therapy for CMV.
· Transplant patients who are re-exposed to TB after transplantation should be assessed for latent infection and/or disease.
· Prophylaxis against MAC may be given, when the CD4+ count is ≤ 50 cells/µL, and stopped when the CD4 count is >100 cells/µL for 6 months.
Monitoring kidney function post transplantation
· Should follow the existing guidelines
Monitoring of HIV virology
· Quantitative HIV RNA and CD4+ T-cell counts should be measured at 1 month after transplant and every 2-3 months for the first year then every 3-6 months.
· If persistent HIV viraemia, drug-resistance testing should be performed.
Choice of living versus deceased donor
· Patients with HIV infection are candidates for living donor kidney transplantation as non-infected patients but are considered unsuitable.
Consent and confidentiality
· In HIV-positive transplant candidates you should follow the standard of consent as for any other transplant candidate.
· All living donors should be aware that there may be confidential information about the recipient (not relevant to the transplant outcome) which are not disclosed.
· If possible, the recipient is asked to disclose their diagnosis of HIV to their donors.
Use of HIV-infected donors for HIV-infected recipients
· Patients with HIV-infection are unsuitable for living kidney donation.
· Deceased donors should have HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury.
· If possible Information such as genotype and current viral load should be obtained.
· Should have no history of virological failure or drug resistance.
I like your clinical approach and well-structured detailed summary.
Summary
Introduction
This article involves recommendations and suggestions regarding kidney and pancreas transplant in HIV patients. The following are updated guidelines with respect to this topic by the British Transplantation Society. The aim is to cover all aspects of assessment, selection and management of HIV positive transplant recipients.
Summary of the main aspects of this article :
Indications for kidney transplant
Indications for pancreatic transplantation
Contraindications to transplant
Absolute contraindications
Relative contraindications
Assessment
Immunisation before transplant
Immunosuppression and prophylaxis
Donor criteria
Consent
I like your clinical approach and well-structured detailed summary.
Indications for Kidney transplantation
Recommendations:
• Screen all KTR for HIV infection (1D)
• HIV is not a contraindication for KT (1B)
• HIV-positive patients are wait-listed only if:
a) Commenced on cART therapy (1D)
b) Stable CD4+ T count in the past 3 months >100 cells/μL (ideally > 200 cells/ μL) (1B)
c) Undetectable HIV RNA in last 6 months (1B)
d) No opportunistic infections in last 6 months (1B)
e) No previous PML, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Suggestions:
• cART to be discussed and determined before KT (Not graded)
Indications for Pancreas Transplantation
Recommendations:
• Pancreas recipients should be assessed in center expert in KT for HIV-positive patients, and also in pancreas or islet transplantation (Not graded)
Suggestions:
Diabetics with controlled HIV can be considered for:
• Simultaneous KPT if they have renal failure (2D)
• if they have severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if kidney function is stable. (Not graded)
Contraindications to transplantation
• Absolute contraindications to KT in patients with HIV:
a) Uncontrolled HIV infection; persistently CD4+ <100 cells/μL in last 6 m & persistent HIV RNA detectable in last 3 months (1C)
b) Habitual and irremediable non-concordance with treatment (1D)
c) Resistance HIV infection to available (1D)
d) Positive CDC crossmatch (1D)
e) Serious ongoing or recurring infection PML (1D)
f) Malignancy( active or disseminated ) (1D)
g) Pregnancy (1D)
• Relative contraindications to KT:
a) Positive FCXM (1D)
b) ABOi (2D)
c) Treated malignancy; including Kaposi sarcoma (2C)
d) Uncontrolled medical problems (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
General assessment
• Recommended to follow existing guidelines for all candidate with HIV disease (Not graded)
HIV-specific assessment
Recommendations:
• Evaluate virological and cART status; CD4 cell count, HIV RNA level, resistance profile and cART history (1D)
• If HIV RNA <200 copies/mL, considered Tx if fully adherent with medications (1C)
• Serology for syphilis, HSV, EBV, CMV, VZV, HTCLV, Toxoplasma gondii & Strongyloides stercoralis (1D)
• TB screening & treatment prior to Tx ( active and LTBI); with IGRA +/- TST (1C)
• Screened for viral hepatitis; If serology positive to confirm with NAT and to look for cirrhosis (1C)
• HBsAg positive patients to receive treatment and ensure viral suppression (1B)
• Screen & treat for cervical and/or anal neoplasia (1D)
• SOT can be considered if HIV RNA suppressed & CD4 < 200 but >100 cells/μL (2C)
• Avoid antiretrovirals with nephrotoxic potential or drug-drug interactions.
• Anti-HBc positive “alone” recipients do not require prophylaxis unless reactivation risk is high.
Pancreas-specific assessment
• Should performed in experience center with HIV patients.
• Pancreas Tx assessment in patients with HIV includes: detailed diabetic assessment, vascular assessment
& cardiac assessment (2C)
Pre-transplant immunization
Recommendation:
• HBV vaccine to all patients if HBVsAb <10 mIU/mL (1B)
• HAV vaccine (for non-immune) (1D)
• PPV-23 (1B)
• VZV vaccine (non-immune ) with CD4 >200 cells/μL (1C)
• Influenza vaccine annually (1B)
Suggested:
• DTP to all patients (2D)
• MMR (nonimmune) (2D)
• HPV for high risk (2C)
Consideration of drug-drug interactions
• Recommended to consider cART in the perioperative period (1D)
• Medication review as part of the assessment (Not graded)
• CNI trials to determine optimum doses (2D)
• Switching from PI regimens to minimize drug interactions (2D)
Induction and maintenance immunosuppression
• Induction therapy offered to All KTR with HIV-positive at time of Tx1C)
• Induction therapy is with IL-2RA (1B)
• Triple maintenance IS started at the time of kidney transplantation
• Acute rejection is treated the same way as HIV-negative KTR (2D)
Post-transplant prophylaxis
• lifelong prophylaxis against PCP (1D)
• CMV prophylaxis; if CMV R-/ D+ for of 3 months (1A)
• Recipient CMV positive; either prophylaxis or surveillance and pre-emptive therapy for 3 mo(1A)
• Assess and treat LTBI prior to transplantation, revaluate if new exposure history or symptoms develop, and treat as per NICE guidelines (1C)
• Toxoplasma lifelong prophylaxis if either donor is positive or recipient positive & CD4 <200 (2C)
• MAC prophylaxis; if CD4 count ≤ 50. To be stopped when the count is >100 cells/μL for 6
months (2D)
Monitoring allograft function
• Follow the current guidelines for post-operative care of the KTR (Not graded)
Monitoring virological control
• Post-Tx regular measurement of: HIV RNA and CD4+ T-cell counts, at 1 month then q 2-3 months for the first year then every 3-6 months (1B), more frequent if receiving antibody depleting to assess the need for prophylaxis (2D)
• If viremia persistent HIV, test for drug-resistance (1D)
Choice of living versus deceased donor
• Access to living donor KT should be the same as non-infected patients. (1B)
• HIV donors are unsuitable for donation (1D)
• Disclosure of the recipient’s HIV status is not mandatory (Not graded)
Consent and confidentiality
• Follow the current guidelines on the ethics for all donors (Not graded)
• Donor consent should be adequate and transparent and established in advance (Not graded)
• Encourage the recipient to disclose HIV diagnosis to their donor (Not graded)
• Donors are asked about any condition cause them to change their decision to donate, without highlighting HIV (Not graded)
• Donors should be aware about that medical and social or confidential information about the recipient that is not disclosed (Not graded)
Use of HIV-infected donors for HIV-infected recipients
• Using HIV-infected organs is restricted to organs from DD with:
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to
brain injury
b) Genotype patterns where possible and current viral load
c) No virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent (1D)
• LD with HIV-infection are considered for donation (1D)
• The use of HIV+ organ is restricted to experience centers (Not graded)
I like your well-structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
This is a British protocol with the strategy of carrying out a systematic review to define protocols and guidelines for patients living with the HIV virus who are going to undergo a kidney-pancreas transplant or just the first one.
Indications for Kidney Transplantation
Recommendations:
– Everyone should be screened for HIV
– In isolation, it is no longer contraindicated
– Must have a negative viral load for six months, CD4 count greater than 100 (ideally above 200) for three months, no opportunistic infections in the last six months, and no history of PML, lymphoma, or intestinal infection by Cryptosporidium.
Suggestive
Prior evaluation by an infectologist to choose the ideal HAART and its interactions
Indications for pancreas transplantation
– It is recommended to be in a center with experience in HIV patients and kidney transplantation
– It is suggested that for diabetic patients the transplant is associated with the kidney
Contraindications to transplantation
– Uncontrolled HIV infection
– Major psychiatric illness
– Multiple resistance in HIV Genotyping and low availability of medications
– CDC positive
– Pregnancy
– Active malignant disease
Relative contraindications
– positive FCXM
– ABOi
– Kaposi’s sarcoma
– Uncontrollable illness with difficulty in recovery
– chronic liver disease
– BMI greater than 35
– Coinfection with the HTLV virus
Related to HIV
– Frequent measurement of CD4 levels and viral load
– Other serologies should be performed, including latent tuberculosis
– If IGRA positive, proceed with an investigation for active tuberculosis
– Serologies for Hepatitis B and C
– Investigation of cervical/anal neoplasia
Contraindication
– Transplantation in patients with liver cirrhosis or hepatitis C virus replication
– Castleman disease or EBV or HHV8 lymphomas
Suggestions
– Some cases consider CD4 above 100 as applicable to transplantation
– Avoid nephrotoxic antiretroviral formulations
– Evaluate drug interactions with immunosuppressants
Pre-transplant immunization
– HBV vaccine if HbAb < 10mIU/mL
– HAV vaccine if negative serology
– PPV-23 and Influenza
– VZV vaccine if CD4 more than 200 cells
– Consider DPTa, MMR and HPV
immunosuppression
– All HIV-positive patients should undergo induction, if possible with IL2RA
– Triple scheme is the most suitable Tacrolimus + MMF + Prednisone
– Treat acute rejection similarly to non-HIV patients
Prophylaxis
– Pneumocystosis for life (includes toxoplasmosis)
– CMV for three months (prophylaxis or pre-emptive)
– latent tuberculosis
– Mycobacterium avium if CD4 count less than 50 cells
HIV-positive patients have similar access to the donation waiting list. If there is a donation between a donor and recipient positive for HIV, there is a need for extensive investigation and both have no history of resistance to antiretrovirals.
I appreciate your emphasis on ‘equity of distribution’ of donor organs irrespective of prospective recipient’s HIV status.
HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months (1B)
c) HIV RNA has been undetectable during the previous 6 months (1B)
d) No opportunistic infections have occurred during the previous 6 months (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma (1B)
Contraindications to transplantation
• The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months) (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch (1D)
e) Serious ongoing or recurring infection, including documented history of PML (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer (1D)
g) Pregnancy (1D)
The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM) (1D)
b) Blood-type incompatibility (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy (2D)
e) Chronic liver disease (2D)
f) Marked obesity (BMI >35 kg/m2) (2D)
g) HTLV infection (1D)
Transplant candidates undergo serologic □testing for syphilis,
□herpes simplex virus,
□Epstein-Barr virus,
□cytomegalovirus,
□varicella zoster virus,
□human T-cell leukaemia virus
□Toxoplasma gondii
■ Transplant candidates who test positive for latent TB are assessed for any evidence of active tuberculosis disease (1C)
■ Transplant candidates with evidence of active tuberculosis disease are treated prior to transplantation (1C)
◇All transplant candidates are screened for viral hepatitis.
◇Those found to be HBsA or HCV antibody positive should have their HBV DNA / HCV RNA levels quantified and be investigated for the presence of liver cirrhosis (1C)
◇Anti-HBc positive “alone” recipients (donor negative), do not require routine antiviral prophylaxis (2D)
♧ Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; treatment prior to transplantation (1D)
●SoT may be appropriate for patients with fully suppressed HIV RNA and a CD4 cell count below 200 cells/µL but above 100 cells/µL (2C)
● Antiretrovirals with nephrotoxic potential (specific tenofovir formulations and atazanavir) are avoided if suitable alternatives are available (Not graded)
●Antiretrovirals with significant drug-drug interactions with cNI (ritonavir and cobicistat) are avoided if suitable alternatives are available (2D)
Pre-transplant immunisation (vaccination)
• (HBV) vaccine
• (HAV) vaccine
• (PPV-23) vaccine
• (VZV) vaccine
• Influenza vaccine
• (DTP) vaccine
• (MMR) vaccine
• (HPV) vaccine
Induction and maintenance immunosuppression
• For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA) (1B)
• HIV-positive patients are given triple therapy maintenance immunosuppression
• Acute rejection is treated in HIV-positive kidney transplant recipients in the same way as HIV-negative kidney transplant recipients (2D)
Post-transplant prophylaxis
♤ Pneumocystis pneumonia ==> lifelong prophylaxis
♤CMV R (NEG ) FROM D (POS) ==> for a minimum of 3 months
♤CMV R (POS) ==> either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months
♤TB re-exposed after transplantation ==> should be assessed for latent infection and/or disease as recommended in current NICE TB guidance
♤Toxoplasma IgG seropositive recipients with a CD4+ count <200 cells/µL ==> lifelong prophylaxis
♤donor seropositive for toxoplasmosis ==> recipient lifelong prophylaxis
♤Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months (2D)
Monitoring allograft function
• Existing guidelines regarding post-operative care of the kidney transplant recipient are followed for all kidney transplant recipients with HIV disease (Not graded)
Monitoring of HIV virological control
Quantitative HIV RNA and CD4+ T-cell counts:
○ the first assays at 1 month after ○transplant subsequent every 2-3 months for the first year
○ every 3-6 months thereafter
However, More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies
Choice of living versus deceased donor
• Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients (1B)
• Patients with HIV infection are unsuitable to be living kidney donors (1D)
Consent and confidentiality
• Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease (Not graded)
• All living donors are asked whether there are any medical conditions that would cause them to change their decision to donate, without highlighting HIV (Not graded)
Use of HIV-infected donors for HIV-infected recipients
: • Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load <50 copies/mL and CD4 count >200/µL for at least 6 months prior to brain injury
b) Information about the donor virus such as historical genotype patterns where possible and current viral load
c) No history of virological failure or drug resistance (1D)
• Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation (1D)
• HIV+ organ use is restricted to those centres that have experience in transplanting HIV+ patients (Not graded)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Kidney & Pancreas Transplantation in Patients with HIV
Summary
HIV infection is not a contraindication for kidney transplantation but screening is
mandatory for all potential recipients
:HIV-positive patients are wait-listed only in the following situations
Have CD4+ T cell counts >100 cells/µL –
Have been stable during the previous 3 month –
Have undetectable HIV RNA –
Have no opportunistic infections –
-Have no history of progressive multifocal leukoencephalopathy, chronic intest –
cryptosporidiosis, or lymphoma.
It is suggested that antiretroviral therapy needs to be appropriately determined before transplantation to anticipate potential drug interaction
Indications for Pancreas Transplantation:
Potential HIV positive pancreas transplant recipients should be assessed by a centre with experience in kidney transplantation in HIV-positive patients and also in solitary
pancreas or islet transplantation
Diabetic patients in renal failure and with controlled HIV infection may be considered for
simultaneous or solitary pancreas transplantation, as long as they have stable and preserved eGFR >40mL/min
Contraindications to kidney transplantation in patients with HIV include:
General assessment
Pancreas-specific assessment
Consideration of drug-drug interactions
Afull and current medication review for solid organ transplantation is recommended , a dose-finding trial of calcineurin-inhibitors prior to transplantation, pre-emptive switching away from PI-based antiretroviral regimens, and a footer referring practitioners to the Liverpool HIV Drug Interactions Resource.
Induction and maintenance immunosuppression
Post-transplant prophylaxis
Monitoring allograft function:
Choice of living versus deceased donor:
Consent and confidentiality:
Use of HIV-infected donors for HIV-infected recipients:
I. Kidney & Pancreas Transplantation in Patients with HIV
Please summarize this article.
Indications for KTX
Recommendations:
• The HIV status of all KTX candidates is checked. (1D)
• HIV does not preclude KTX. (1B)
• HIV+ve patients are waitlisted only if:
Suggestions:
• The best HAART is chosen pre-TX so as to foresee drug interactions & select the right dosages. (Not graded)
=====================
Indications for Pancreas Transplantation
Recommendations:
• A center with experience in both solitary pancreas or islet TX & KTX in HIV+ve patients evaluates potential HIV +ve pancreas TX recipients. (Not graded)
Suggestions:
• SKP TX is an option for diabetic patients with renal failure & treated HIV infection. (2D)
• If a diabetic patient’s HIV is under control & renal function is stable (eGFR >40mL/min), a single pancreas or islet TX may be considered. (Not graded)
=====================
Contraindications to transplantation
Recommendations:
• Absolute contraindications:
Suggestions:
• Relative contraindications:
=====================
General assessment
Recommendations:
• Adherence to the current standards for evaluation, selection, & preparation of the TX recipient. (Not graded)
=====================
HIV-specific assessment
Recommendations:
• Careful virological & antiretroviral status review (CD4 cell count, HIV RNA level,& HAART, HLA-B5701 status & HIV resistance profile (1D)
• If HIV RNA levels <200 copies/mL, SOT TX is possible if otherwise well & adherent with medications (1C)
• Serologic testing for syphilis, HSV, EBV, CMV, VZV, HTLV, & Toxoplasma gondii is performed. (1D)
• According to NICE guidelines, TX candidates are screened for latent MBT with an interferon-gamma test +/- Mantoux test. (1C)
• Latent MTB+ve candidates are examined for signs of active TB. (1C)
• Active TB disease treated according to current NICE guidance pre-TX. (1C)
• NICE TB recommendations: latent MB infection, after excluding active disease, is treated for before TX. (1C)
• Screened for viral hepatitis: If HBsAg or HCV antibody positive, HBV DNA/HCV RNA levels measured & checked for liver cirrhosis (1C)
• Those with HBsAg on the waiting list for SOT should get therapy to clear HBV DNA completely. (1B)
• Cervical &/or anal neoplasia in patients being considered for SOT is evaluated; advanced neoplasia (CIN/AIN III) or carcinoma treated before TX. (1D)
We recommend against:
• Kidney &/or pancreas TX in patients with liver cirrhosis (1B) & in those with evidence of active HCV replication (1C)
• SOT in patients with a H/O Castleman’s disease, HHV8-related primary effusion lymphoma or EBV-related lymphoma (1D)
Suggestions:
• Patients with totally suppressed HIV RNA & CD4 cell < 200 cells/L but > 100 cells/L may in some circumstances be candidates for SOT. (2C)
• If acceptable substitutes are available, antiretrovirals with nephrotoxic potential (tenofovir & atazanavir) are avoided. (Not graded)
• If adequate substitutes are available, antiretrovirals with strong drug-drug interactions with CNI (ritonavir & cobicistat) should be avoided. (2D)
• Strongyloides stercoralis infection is checked in candidates from endemic areas. (2D)
• Anti-HBc +ve “alone” recipients (donor -ve, recipient sAg & DNA -ve): routine antiviral prophylaxis not required, but may be considered if increased risk of reactivation (e.g. those receiving lymphodepletion therapy) (2D)
=====================
Pancreas-specific assessment
Recommendations:
• Only centers routinely performing pancreas & KTX in HIV patients should assess such potential TX recipients. (1C)
• Inform TX candidates that there is limited experience of pancreas TX in HIV-infected patients (Not graded)
Suggestions:
• Pancreas TX assessment in patients with HIV:
=====================
Pre-transplant immunization
Recommendations:
• HBV vaccine for all non-immune patients (HBV surface antibody <10 mIU/mL) (1B)
• HAV vaccine for all non-immune patients (1D)
• PPV-23 for all patients (1B)
• VZV vaccine for non-immune patients with CD4 cell counts >200 cells/μL (1C)
• Influenza vaccine annually to patients awaiting SOT (1B)
Suggestions:
• DDTP vaccine for all patients (2D)
• MMR vaccine for those all non-immune to measles (2D)
• HPV vaccine for at risk patients (2C)
=====================
Consideration of drug-drug interactions
Recommendations:
• Continue antiretroviral therapy in the perioperative time post-TX (1D)
Suggestions:
• A thorough review of all current medications to be done at least twice a year afterward & at each significant therapeutic decision point. (Not graded)
• A dose-finding trial of CNI prior to SOT in order to find an optimum doses to initiate post-TX (2D)
• If alternatives are available, switching from boosted PI-based HAART regimens in advance to minimize medication interactions (2D)
• A footer directing doctors to the Liverpool HIV Drug Interactions Database should appears on all clinical communication (www.hiv-druginteractions.org) (Not graded)
=====================
Induction and maintenance immunosuppression
Recommendations:
• Induction therapy is provided to all HIV-+ve patients who are eligible for KTX. (1C)
• Induction therapy is with IL-2RA for the majority of HIV +ve patients (1B)
• HIV+ve individuals are given triple therapy maintenance IS (steroids, a CNI, & an anti-proliferative drug). (1C)
Suggestions:
• HIV+ve KTX recipients who experience AR are treated similarly to HIV-ve recipients. (2D)
=====================
Post-transplant prophylaxis
Recommendations:
• HIV-positive TX recipients receive lifetime Pneumocystis pneumonia prevention. (1D)
• In CMV -ve recipients from CMV +ve donors, prophylaxis against CMV is advised for a minimum of 3 months. (1A)
• For a minimum of 3 months, CMV +ve TX recipients receive either prophylaxis against CMV infection or PCR surveillance & preventive medication. (1A)
Patients who are healthy but have not had their MTB latent infection or disease evaluated & treated before TX should do so after TX. (1C)
• Unless there is a new H/O exposure to TB, TX patients who are healthy & were previously diagnosed with & treated for MBT latent infection or illness do not require review for latent infection. (1C)
• NICE TB guidance on TB contact tracing: TX patients who are re-exposed to TB after TX should be evaluated for MBT latent infection &/or disease. (1C)
Suggestions:
• Lifelong prophylaxis for any recipient of an organ from a donor positive for toxoplasmosis or who has a toxoplasma IgG serology & a CD4+ count < 200 cells/L. (2C)
• When a previous diagnosis of successfully treated TB is present, only a chest X-ray & symptoms review are required; TB prophylaxis is not necessary unless TB re-exposure is suspected. (2D)
• When CD4+ level is < 50 cells/L, MAC prophylaxis is recommended. It should be discontinued after 6 months if CD4+ count is > 100 cells/L. (2D)
=====================
Monitoring allograft function
Recommendations:
• Current guidelines for post-operative care of the KTX recipient are followed for all KTX recipients with HIV disease (Not graded)
Suggestions:
• Follow local protocol for pancreatic allograft monitoring (Not graded)
=====================
Monitoring of HIV virological control
Recommendations:
Regular measurements of HIV RNA & CD4+ T-cell counts are made; the initial tests performed 1 month after TX & then every 2-3 months for the first year & every 3-6 months after that. (1B)
• Drug-resistance testing is done on patients with chronic HIV viraemia to assess therapy choices. (1D)
Suggestions:
• To evaluate if a patient needs anti-infective prophylaxis while receiving depleting antibodies, more frequent CD4 count monitoring may be required. (2D)
=====================
Choice of living versus deceased donor
Recommendations:
• HIV-positive patients have the same access to LD KTX as non-infected patients (1B)
• HIV-positive persons are unacceptable as LKDs (1D)
Suggestions:
• The medical, surgical, & psychosocial aspects that increase the recipient’s risk of morbidity & mortality are disclosed to potential donors, but not necessarily the recipient’s HIV status. (Not graded)
=====================
Consent & confidentiality
Recommendations:
• The current standards for LD & DD transplant ethics are adhered to. (Not graded)
• For HIV+ve TX candidates, the same standards of consent apply as for any other TX. (Not graded)
• Methods for obtaining acceptable donor consent should be transparent & pre-established. (Not graded)
Suggestions:
• Recipients are urged to inform their donors of their HIV diagnosis whenever feasible. (Not graded)
• Without specifically mentioning HIV, all LDs are asked about any issues that would make them reconsider donating. (Not graded)
• LDs are informed that the recipient’s medical & social history might not be shared. (Not graded)
• LDs should certify that they are aware that they will not be given private information about the recipient that is not thought to be important to the KTX recipient’s prognosis. (Not graded)
=====================
Use of HIV-infected donors for HIV-infected recipients
Recommendations:
• TX using organs from HIV-infected individuals is restricted to organs from DDs with:
Suggestions:
• Only facilities with experience transplanting HIV+ patients are allowed to use HIV+ organs. (Not graded)
I appreciate your very detailed structured summary.
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
BTS Guidelines for Kidney & Pancreas Transplantation in Patients with HIV:
Indications for Kidney transplantation:
-All potential kidney transplant recipients are screened for HIV infection. (1D)
-HIV per se is not a contraindication for kidney transplantation. (1B)
-HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy. (1D)
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months. (1B)
c) HIV RNA has been undetectable during the previous 6 months. (1B)
d) No opportunistic infections have occurred during the previous 6 months. (1B)
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma. (1B)
Contraindications to transplantation:
The following are absolute contraindications to kidney transplantation in patients with HIV:
a) Uncontrolled HIV infection (CD4+ T cell levels persistently < 100 cells/µL during the last 6 months and HIV RNA persistently detectable during the last 3 months). (1C)
b) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse. (1D)
c) Multi-drug resistant HIV infection that cannot be controlled with currently available ART. (1D)
d) Positive complement-dependent cytotoxic (CDC) crossmatch. (1D)
e) Serious ongoing or recurring infection, including documented history of PML. (1D)
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer. (1D)
g) Pregnancy. (1D)
The following are relative contraindications to kidney transplantation:
a) Positive flow cytometric crossmatch (FCXM). (1D)
b) Blood-type incompatibility. (2D)
c) Treated malignancy, including extracutaneous Kaposi sarcoma. (2C)
d) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy . (2D)
e) Chronic liver disease. (2D)
f) Marked obesity (BMI >35 kg/m2 ) . (2D)
g) HTLV infection. (1D)
General assessment:
-Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease. (Not graded)
HIV-specific assessment:
-All transplant candidates undergo careful immuno-virological and antiretroviral status review. This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile. (1D)
-Patients with HIV RNA levels < 200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications. (1C)
-Transplant candidates undergo serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii. (1D)
-Transplant candidates are tested for latent Mycobacterium tuberculosis infection with an interferon-gamma test with or without a concurrent Mantoux test following the testing strategy for immunocompromised patients in the current NICE Tuberculosis Guidelines. (1C)
-Transplant candidates who test positive for latent Mycobacterium tuberculosis infection are assessed for any evidence of active tuberculosis disease. (1C)
-Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation. (1C)
-Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation. (1C)
-All transplant candidates are screened for viral hepatitis. Those found to be hepatitis B surface antigen or hepatitis C antibody positive should have their hepatitis B DNA / hepatitis C RNA levels quantified and be investigated for the presence of liver cirrhosis. (1C)
-All hepatitis B surface antigen positive patients who are wait listed for solid organ transplantation receive treatment to ensure hepatitis B DNA is fully suppressed. (1B)
-Patients considered for solid organ transplantation are assessed for the presence of cervical and/or anal neoplasia; those with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or carcinoma in situ should receive treatment prior to transplantation. (1D)
Recommendations against:
-Kidney and/or pancreas transplantation in patients with liver cirrhosis, (1B)
and in those with evidence of active HCV replication. (1C)
-Solid organ transplantation in patients with a history of Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)- related lymphoma. (1D)
Pre-transplant immunization:
-Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres < 10 mIU/mL). (1B)
-Hepatitis A virus (HAV) vaccine is administered to all non-immune patients. (1D)
-Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients. (1B)
-Varicella zoster vaccine (VZV) vaccine is administered to non-immune patients with CD4 cell counts >200 cells/µL. (1C)
-Influenza vaccine is administered annually to patients awaiting solid organ transplantation. (1B)
Consideration of drug-drug interactions:
-Continuation of antiretroviral therapy in the perioperative period following transplantation. (1D)
-A dose-finding trial of calcineurin-inhibitors prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant. (2D)
-Pre-emptive switching away from boosted protease-inhibitors (PI)-based antiretroviral regimens, if alternatives exist, in order to minimise drug interactions. (2D)
Induction and maintenance immunosuppression:
-All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation. (1C)
-For the majority of HIV-positive patients induction therapy is with an interleukin-2 receptor antagonist (IL-2RA). (1B)
-HIV-positive patients are given triple therapy maintenance immunosuppression started at the time of kidney transplantation, including steroids, a calcineurin inhibitor (CNI) and an anti-proliferative agent. (1C)
Post-transplant prophylaxis:
-HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation. (1D)
-Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months. (1A)
-CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months. (1A)
-Transplant patients who are well and were not assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation should be assessed as recommended for patients prior to transplantation. (1C)
-Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis. (1C)
-Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing. (1C)
-Toxoplasma IgG seropositive recipients with a CD4+ count < 200 cells/µL or any recipient of an organ from a donor seropositive for toxoplasmosis receive lifelong prophylaxis. (2C)
-Where there is a reliable prior history of treated TB infection there is no need for further testing beyond symptom review and chest X-ray, and these individuals do not require TB prophylaxis unless TB re-exposure is suspected. (2D)
-Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ ≤ 50 cells/µL, and it be stopped when the CD4 count is >100 cells/µL for 6 months . (2D)
Monitoring of HIV virological control:
-Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year then every 3-6 months thereafter. (1B)
-If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options. (1D)
Choice of living versus deceased donor:
-Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients. (1B)
-Patients with HIV infection are unsuitable to be living kidney donors. (1D)
Consent and confidentiality:
-Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease. (Not graded)
-The standard of consent for HIV-positive transplant candidates is the same as for any other transplant.(Not graded)
-Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance. (Not graded)
Use of HIV-infected donors for HIV-infected recipients:
-Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with:
a) HIV viral load < 50 copies/mL and CD4 count > 200/µL for at least 6 months prior to brain injury,
b) Information about the donor virus such as historical genotype patterns where possible and current viral load,
c) No history of virological failure or drug resistance. (1D)
-Recipients are counselled and give informed consent both at the time of listing and at the time of transplantation. (1D)
-Patients with HIV-infection are unsuitable to be living kidney donors. (1D).
Yes I like your well structured detailed summary.
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.
Introduction for kidney transplantation
We recommend that: All potential kidney transplant recipients are screened for HIV infection.
HIV per se is not a contraindication for kidney transplantation.
HIV-positive patients are wait-listed only if: A) They are concordant with treatment, cART therapy
B) Their CD4+ T cell counts are >100 cells/μL and have been stable during the previous 3 months
C) They have no history of progressive multifocal leukoencephelopathy, chronic intestinal cryptosporidiosis, or lymphoma.
We suggest that: The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication.
Indications for pancreas transplantation
Potential HIV positive pancreas transplant recipients are assessed by a centre with experience in kidney transplantation in HIV-positive patients, and in solitary pancreas or islet transplantation.
Diabetic patients in renal failure and with controlled HIV infection are considered for simultaneous kidney and pancreas transplantation.
Diabetic patients with severe hypoglycaemic unawareness may be considered for solitary pancreas or islet transplantation if they have well controlled HIV and kidney function that is stable and preserved.
Contraindications to transplantation
The following are absolute contraindications to kidney transplantation in patients with HIV:
A) Uncontrolled HIV infection (CD4+ T cell levels persistently <100 cells/μL during the last 6 months and HIV RNA persistently detectable during the last 3 months).
B) Habitual and irremediable non-concordance, due for example to major psychiatric disease, irresolvable psychosocial problems or persistent substance abuse,
C) Multi-drug resistant HIV infection that cannot be controlled with currently available.
D) Severe and/or uncontrolled medical problems that are unlikely to improve after kidney transplantation and will shorten the patient’s life expectancy.
E) Serious ongoing or recurring infection, including documented history of PML .
F) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer.
The following are relative contraindications to kidney transplantation: a) Positive flow cytometric crossmatch (FCXM).
General assessment
Existing guidelines regarding evaluation, selection and preparation of the potential transplant recipient are followed for all potential transplant recipients with HIV disease (Not graded).
All transplant candidates undergo careful immuno-virological and antiretroviral status review
This includes CD4 cell count, HIV RNA level, current and prior antiretroviral therapies, HLA-B5701 status and HIV resistance profile .
Patients with HIV RNA levels <200 copies/mL may be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications.
Transplant candidates with evidence of active tuberculosis disease are treated according to current NICE guidance prior to transplantation.
Transplant candidates with latent Mycobacterium tuberculosis infection, in whom active disease has been excluded are treated for latent Mycobacterium tuberculosis infection, according to current NICE TB guidelines, prior to transplantation.
Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titres <10 mIU/mL).
That all clinical correspondence carries a footer referring practitioners to the Liverpool
Induction and maintenance immunosupression
All HIV-positive patients eligible for kidney transplantation are offered induction therapy at the time of transplantation.
HIV-positive transplant recipients receive lifelong prophylaxis against Pneumocystis pneumonia following transplantation.
Prophylaxis against cytomegalovirus is indicated in CMV seronegative recipients of organs from CMV seropositive donors for a minimum of 3 months.
CMV seropositive transplant recipients receive either prophylaxis against CMV infection or PCR surveillance and pre-emptive therapy for a minimum of 3 months.
Transplant patients who are well and were assessed and treated for Mycobacterium tuberculosis latent infection or disease before transplantation do not need reassessment for Mycobacterium tuberculosis latent infection unless there is a new history of exposure to tuberculosis.
Transplant patients who are re-exposed to tuberculosis after transplantation should be assessed for Mycobacterium tuberculosis latent infection and/or disease as recommended in current NICE TB guidance on tuberculosis contact tracing.
Count is ≤ 50 cells/μL, and it be stopped when the CD4 count is >100 cells/μL for 6 months.
Monitoring of HIV virological control
Quantitative HIV RNA and CD4+ T-cell counts are measured regularly, with the first assays at 1 month after transplant and subsequent studies every 2-3 months for the first year every 3-6 months thereafter.
If patients have persistent HIV viraemia, drug-resistance testing is carried out to determine treatment options.
More frequent monitoring of CD4 count may be necessary in patients receiving depleting antibodies to determine the need for anti-infective prophylaxis.
Choice of living versus deceased donor
Patients with HIV infection have the same access to living donor kidney transplantation as non-infected patients.
Patients with HIV infection are unsuitable to be living kidney donors.
Potential donors for patients with HIV infection are informed of medical, surgical, and psychosocial factors that may heighten the recipient’s morbidity and mortality risk but that disclosure of the recipient’s HIV status is not mandatory.
Consent and confidentiality
Existing guidelines on the ethics of deceased donor and living donor transplantation are followed for all transplantation involving people with HIV disease.
The standard of consent for HIV-positive transplant candidates is the same as for any other transplant .
Transplant teams must be satisfied that donor consent is adequate and that procedures for ensuring this are transparent and established in advance.
Yes I like your well structured detailed summary.
I appreciate that HIV positive recipients are assessed and treated for Mycobacterium tuberculosis latent infection.
Kidney transplant indications:
> All kidney transplant candidates should be HIV-screened (1D)
HIV does not exclude kidney transplantation (1B)
• HIV-positive individuals are wait-listed only if: a) They comply with treatment, especially cART therapy (1D)
b) Their CD4+ T cell counts are >100 cells/μL (preferably > 200) and have remained steady for 3 months (1B)
c) HIV RNA was undetectable for 6 months (1B)
d) No opportunistic infections in 6 months (1B)
e) No progressive multifocal leukoencephalopathy, persistent intestinal cryptosporidiosis, or lymphoma history (1B)
Pancreas transplant indications:
• Prospective HIV-positive pancreatic transplant candidates should be evaluated by a center with expertise in kidney and solitary pancreas or islet transplantation (Not graded)
Transplant contraindications
HIV-positive people cannot have kidney transplantation:
a) Uncontrolled HIV infection (CD4+ T cell levels <100 cells/μL for 6 months and HIV RNA for 3 months) (1C)
b) Persistent non-concordance owing to serious mental disorder, psychological issues, or drug addiction (1D)
c) Multi-drug resistant HIV infection uncontrollable with current ART (1D)
CDC crossmatch positive (1D)
e) Chronic infection, with PML history (1D)
f) Treatment-resistant, metastatic, disseminated, or untreated cancer (1D)
pregnancy (1D)
HIV testing:
• All transplant candidates should be carefully immuno-virologically and anti-retrovirally assessed. CD4 cell count, HIV RNA level, current and past antiretroviral treatments, HLA-B5701 status, and HIV resistance profile (1D)
• Individuals with HIV RNA levels <200 copies/mL and good treatment adherence may be eligible for solid organ transplantation (1C)
• Transplant candidates are serologically tested for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human T-cell leukemia virus, and Toxoplasma gondii (1D)
• Transplant candidates are evaluated for latent Mycobacterium TB infection using an interferon-gamma test with or without a Mantoux test according to the NICE Tuberculosis Guidelines for immunocompromised patients (1C)
• Latent Mycobacterium tuberculosis-positive transplant candidates are tested for active illness (1C)
• Active TB patients are treated according to NICE guidelines before transplantation (1C)
• NICE TB guidelines recommend treating latent Mycobacterium tuberculosis infection in transplant candidates who have been cleared of active illness before transplantation (1C)
All transplant candidates undergo viral hepatitis screening. • All hepatitis B surface antigen-positive patients who are waitlisted for solid organ transplantation get therapy to completely suppress hepatitis B DNA (1B)
• Solid organ transplant candidates with advanced cervical/anal intraepithelial neoplasia (CIN/AIN III) or cancer in situ should be treated before transplantation (1D)
Avoid:
• Kidney and pancreas transplantation for liver cirrhosis (1B) and HCV replication (1C)
• Solid-organ transplantation in Castleman’s illness, HHV8-related primary effusion lymphoma, or EBV-related lymphoma patients (1D)
Pancreas evaluation
• Potential transplant recipients should be assessed at a center that frequently conducts renal and pancreas transplantation in HIV patients (1C)
• Transplant candidates are carefully counseled and advised that HIV-infected patients have minimal pancreatic transplantation experience (Not graded)
Pre-transplant immunization
• All non-immune patients (HBV surface antibody titers <10 mIU/mL) should get the HBV vaccination (1B)
• All non-immune patients get HAV vaccination (1D)
• All patients get PPV-23/pneumococcal polysaccharide vaccination (1B)
Non-immune patients with CD4 cell counts >200 cells/μL get varicella zoster vaccination (VZV) (1C)
Solid organ transplant candidates get influenza vaccination yearly (1B)
Drug-drug interactions
• Continue Post-transplantation antiretroviral treatment (1D)
induction treatment:
• All HIV-positive kidney transplant candidates get induction treatment (1C)
• Most HIV-positive individuals get IL-2RA induction treatment (1B)
• HIV-positive kidney transplant recipients get steroids, a calcineurin inhibitor (CNI), and an anti-proliferative drug for triple treatment immunosuppression (1C)
Post-transplant prophylaxis:
HIV-positive transplant patients get lifetime Pneumocystis pneumonia prevention (1D)
• CMV seronegative recipients of organs from CMV-positive donors should get cytomegalovirus prophylaxis for three months (1A)
• CMV-positive transplant patients get either prophylaxis or PCR monitoring and pre-emptive medication for at least three months (1A)
17
• Healthy transplant patients who were not screened and treated for Mycobacterium TB latent infection or illness before transplantation should be assessed as indicated (1C)
• Healthy transplant patients who were screened and treated for Mycobacterium TB latent infection or illness before transplantation do not require review unless there is a new history of exposure (1C)
• According to current NICE TB guidelines on tuberculosis contact tracing, transplant patients who are re-exposed should be tested for Mycobacterium tuberculosis latent infection and/or illness (1C)
Allograft monitoring;
• HIV-positive kidney transplant patients should follow post-operative care recommendations (Not graded)
HIV virus surveillance:
• Quantitative HIV RNA and CD4+ T-cell counts are assessed at 1 month after transplant and every 2-3 months for the first year, then every 3-6 months after that (1B)
Drug-resistance testing determines therapy choices for individuals with chronic HIV viremia (1D)
Living or deceased donor?
• HIV-positive individuals should have equal access to live donor kidney transplantation (1B)
Consent, confidentiality:
• HIV-positive patients should follow dead donor and live donor transplantation ethical standards (Not graded)
HIV-positive transplant patients must agree like other transplant candidates (Not graded)
• Transplant teams must be certain that donor permission is sufficient and that processes are transparent and predetermined (Not graded)
HIV-infected donor-recipient pairing
• HIV-infected organs should only be transplanted from dead donors.
a) HIV viral load <50 copies/mL and CD4 count >200/μL for at least 6 months prior to brain injury
b) Donor virus information, including genotyping patterns and current viral load
c) No virological failure or drug resistance (1D)
• Listers and transplanters are counseled and obtain informed consent (1D)
HIV-positive people cannot donate kidneys (1D)
Yes I like your well structured detailed summary.
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and corresponding mode of treatment indicated.