6. A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. His HCV PCR is positive but HBsAg negative.
Outline the workup required to prepare him for renal transplantation.
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Mohammed Sobair
Patient is both HIV positive and HCV PCR positive .
This patient must counseled there’s increase risk of recurrence and rejection with coinfection ,in addition to more risk of rejection and opportunistic infection.
Patient should be started on both HART and DAA before transplantation.
If feasible and no urgency SVR for at least 6month before schedule.
For transplantation
HIV viral load not detectable and CD 4 more than 200cell per MO for at least 3months.
His liver function and ultrasound. Should be done and consult hepatologist is needed
This patient is a ESRD secondary to HIVAN, now HCV positive. This patient can taken for transplantation if certain measures are taken. 1, treat with HAART therapy, Until copies less then 50, CD$+T cell >200, no other opportunistic infections. 2, HCV is not a contraindication for transplantation. Plan to treat with DAAs pre-transplant, peri and post-transplantation. 3, Recipient can take HIV and HCV positive donor. 4, post-transplantation with good monitoring for recurrence, liver function test, and other baseline every 3 to 6 monthly. 5, if persistent viremia the suspect drug resistant and need to proceed for testing. References; 1. Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688.
There is a strong and likely causal association between chronic hepatitis C virus (HCV) infection and glomerular disease Several types of kidney disease have been recognized including mixed cryoglobulinemia, membranoproliferative glomerulonephritis (MPGN), membranous nephropathy ], and polyarteritis nodosa (PAN). Crescentic glomerulonephritis may be superimposed on any of these glomerular lesions.Less commonly, other glomerular lesions have been reported in HCV-infected patients, including focal segmental glomerulosclerosis (FSGS) [], proliferative glomerulonephritis and fibrillary and immunotactoid glomerulopathies ]. In some patients, glomerular disease may be clinically silent https://www.uptodate.com/contents/overview-of-kidney-disease-associated-with-hepatitis-c-virus-infection#!
Hepatitis C may share the same route of transmission as HIV; therefore, coinfection is common with nearly 30% of those with HIV also infected with hepatitis C. Hepatitis C progresses more rapidly in coinfected patients and the higher risk of rejection in HIV+ kidney transplant recipients might require more potent immunosuppression either as prophylaxis against or as treatment of rejection, which may in turn further exacerbate hepatitis C infection and posttransplant liver disease . Additionally, complex interactions between retroviral medications, induction or maintenance immunosuppression, and HCV-mediated effects on liver metabolism contribute to difficult management of drug levels. The published experience is scant regarding the potential deleterious impact of HCV coinfection on the outcome of KTX in HIV+ recipients . It is unknown whether the poorer outcomes seen in the coinfected recipients are due to an additive effect of the separate risks of HIV and HCV or whether there is a potentiating effect of both infections existing together. Coinfection may additionally exacerbate the effect of HCV on the graft. Increases in HCV replication due to immunosuppression or the presence of HIV has been hypothesized to increase the risk of allograft glomerular damage. Additionally, data from existing reports are limited by small sample size, short follow-up and lack of risk-adjusted analyses. Pretransplant treatment of HCV has been recommended since patients who achieve a sustained virologic response before transplant are unlikely to experience HCV reactivation after KTX, and have a lower risk of developing liver disease and HCV-related glomerulonephritis prevention or reversal of HIV-related immunosuppression with antiretroviral treatment has been strongly associated with decreased risk of severe liver-related outcomes or death, the adverse impact of HIV coinfection on HCV disease does not appear to be completely ameliorated by the treatment of HIV infection. So treatment of coinfection in the patient together with full survey about complications of each virus such as liver cirrhosis , malignancy, DM, and other opportunistic infection is mandatory before proceeding to tx with the full investigation and requirement as per guidlines
reference Y. Xia, P. Friedmann , H. Yaffe.Effect of HCV, HIV and Coinfection in Kidney Transplant Recipients: Mate Kidney Analyses. American Journal of TransplantationVolume 14, Issue 9, September 2014, Pages 2037-2047
Outline the workup required to prepare him for renal transplantation.
his recipient has HIV and HCV co-infection. Thus, his workup needs importance to both of these infections. Among HIV-positive kidney transplant recipients, somewhat higher early mortality has been observed for those co-infected with HCV (11.7% vs. 3.9% at 1 year, p=0.09) (2). We thus recommend that kidney transplant candidates are treated for HCV prior to transplantation. The General assessment of this patient would be same as those without these infections. HIV specific evaluation:
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
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)
HCV specific assessment:
Guidelines are against kidney transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
HCV PCR should be quantified
ultrasound SOS Fibroscan needs to be performed to rule out liver cirrhosis, which would obviate his transplant
LFT
Alpha-feto proteins
Mangement HIV management
The recipient needs treatment for his HIV as according to BTS guidelines he needs following before he is eligible for transplant
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
HCV management:
KDIGO guidelines say that “We recommend that all kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation (1A).”
but, since the recipient is also HIC con-infected it would be better to treat HCV pretransplant if possible
General management:
The recipient needs pretransplant vaccination against HBV, HAV, pneumococcus, VZV, influenza HPV, DPT and MMR whichever are applicable
He also requires post transplant prophylaxis esp against pneumocystis and CMV(depending upon status
Induction preferably by interleukin-2 receptor antagonist (IL-2RA)
Avoid ATG
Maintenance by triple immunosuppression
Monitor for drug interaction between HIV, HCV and immunosuppressive drugs
Post transplant follow up
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
We suggest that patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs
HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria
We suggest that patients who develop new-onset proteinuria (either urine protein-creatinine ratio > 1 g/g or 24-hour urine protein > 1 g on 2 or more occasions) have an allograft biopsy with immunofluorescence and electron microscopy included in the analysis
BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV
Co-infected kidney transplant candidates for both HIV and HCV also require an evaluation by hepato-logy and assessment of degree of liver fibrosis, often via transient elasto-graphy or biopsy as indicated. The lengthier and more complex evaluation process can create additional barriers to waiting list for transplant candidates with HIV. Thus, preemptive referral for patients with HIV who have CKD stage 4 is essential. Transplant centers should be sensitive to the complexities of navigating the evaluation process for individuals who are HIV1 and centralized care that involves coordination with subspecialists whenever possible helps overcome barriers for these patients.
1. General assessment for kidney transplantation candidate.
2. Evaluation of presence of cirrhosis and portal hypertension. If positive, combined liver and kidney TX is needed.
3. Start DAA therapy.
4. Other conditions for TX of HIV patients such as viral load below 50 and CD4+ cells above 200, no opportunistic infection, good compliance with drugs and stable condition during the last 6 months are needed.
5. Evaluation for syphilis, HAV, HBV, HSV, CMV, EBV, VZV, HTLV, toxoplasmosis and latent TB should be performed.
6. Screening for malignancies according to age and gender.
7. Complete vaccination according to immunological status.
8. Considering drug interactions, especially among DAA, HAART, CNIs and other immunosuppressant drugs.
9. Rule out HIVAN.
10. Monitoring for HIV and HCV after TX.
Reference:
Sawinski, D. (2020). Kidney Transplantation in Patients with HIV. Kidney360, 1(7). https://doi.org/10.34067/kid.0002112020
The given recipient has both HIV and HCV coinfection…The patient has HIVAN leading to ESRD and CKD..He is planned renal transplantation….
Among HIV positive kidney transplant patients, there are reports of higher early mortality for those with coinfected with HCV….There is a recommendation from the BTS and ATS to treat HCV prior to transplantation…There are excellent reports of successful transplant of HIV/HCV infection after the advent of DAA…
HIV specific work up include – rule out oppurtunistic infection which are active in him, absence of HIV resistance (non responsive to HAART), HIV Viral load not detected or less than 200 copies/ml maybe suitable for transplant (atleast 3 months in a year), CD4 count > 200 cells in 6 months. They should undergo serological testing for syphilis, HSV, EBV, CMV, Toxoplasma, HPV…He should be tested to rule out Latent TBI by IGRA ..
HCV specific assessment – we should make sure that the recipient does not have active HCV infection and those with significant fibrosis F3 and F4 by fibrocan…If there is significant fibrosis kidney transplant alone is contraindicated and there is a need for combined liver kidney transplantation…Baseline LFT, PT INR, AFP, OGD should be done to rule out active infection…the KDIGO recommendation is to treat all HCV recipients of kidney transplant with DAA…This can be done before or even after renal transplantation ..AS the recipient is co infected it is better to treat HCV before renal transplantation…
The general mangement of such a patient would be to get a compatible donor of same blood group with good HLA match and negative DSA to minimize immunosuppression…IL2 receptor antagonist should be used if possible….There is a need to monitor for drug interaction between CART, DAA and immunosuppressive….we should also ensure that the patient are vaccinated against HBV, HAV, pneumococcus, VZV, influenza and COVID…
Routine monitoring of HIV RNA and Cd4 count are done every 3 months after transplant…It is imperative to check the HCV RNA levels also post transplant depending on the time taken to achieve SVR prior to transplantation…. Those with proteinuria after transplant should undergo a renal biopsy to rule out HCV GN …
This patient will need to be evaluated for extra criteria due to HIV and liver status
1- HIV:
– HIV RNA levels<50 copies/mL or undetectable in the last 6 months
– CD4 T-cell counts >200 – stable in last 3months
– Compliance to HAART for last 3months
– No drug resistance
– No opportunistic infection
– No malignity
– Evaluate HAART treatment and use of a protease inhibitor that can be switched.
2 – More careful exclusion of HBV;
– Serology for HBcAg and depending on the result, new tests, with HBV DNA PCR being the most definitive.
3 – Assessment of liver status:
– Exclude decompensated cirrhosis or clinically significant portal hypertension. If existing, associated liver transplantation would have to be evaluated.
Patient is HIV+ (with HIVAN) and HCV+ 1. General assessment for any transplant candidate. 2. Evaluation for severity of liver disease – cirrhosis and portal hypertension – Compensated cirrhosis, and no portal hypertension à isolated kidney transplantation, – Decompensated cirrhosis or clinically significant portal hypertension à combined liver–kidney transplantation. He should be given DAA therapy, either before or shortly after transplantation. 3. HIV related inclusion criteria for work up – HIV RNA levels<50 copies/mL or undetectable in last 6 months – CD4 T-cell counts >200, stable in last 3months – Compliance to HAART for last 3months – No h/o drug resistance – No opportunistic infection / PML/ cryptosporidium / lymphoma 4. Infection screening: 4.A – Serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii. 4.B – Rule out TB: IGRA / Quantiferon-TB gold test (+/- Montoux) for latent TBI – If positive for LTBI, assessed for any evidence of active TB disease. – Treatment of LTBI / active TBI as per NICE Tuberculosis Guidelines. 5. Cancer Screening – 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. 6. Immunization / Vaccination HBV and Hep AV vaccines if non-immune Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients. Varicella zoster vaccine is given to non-immune patients with CD4 cell counts >200 cells/µL. Influenza vaccine is administered annually to patients awaiting solid organ transplantation Diphtheria, pertussis, tetanus (DPT) vaccine is administered to all patients Measles, mumps, and rubella (MMR) vaccine is given if he is nonimmune to measles. 7. A dose-finding trial of CNI prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant Pre-emptive switching from boosted protease-inhibitors (PI)-based antiretroviral regimens, if possible, to minimize drug interactions. 8. Access to medications and ability for regular follow up 9. Counselling for recurrence of HIVAN and graft loss 10. Immunosuppression plan: – induction with Basiliximab and maintenance with TAC, MMF and steroids 11. Regular follow up and monitoring – PCP prophylaxis life-long required – monitoring CD 4 counts, HIV RNA, HCV RNA, CNI drug level, RFT, proteinuria, LFT – 3monthly – AFP and liver USG every 6months References: 1. KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE 2. British Transplantation Society Guidelines 2017. Kidney & Pancreas Transplantation in Patients with HIV
3. Kumara N R, Stosor V. Organ transplantation in persons with HIV. AIDS 2020, 34:1107–1116
Outline the workup required to prepare him for renal transplantation.
The first step will be detailed counselling regarding the pros and cons. Criteria for transplantation include –
No history of opportunistic infections
No active cirrhosis and active HCV replication
CD 4 count more than 200 copies/Ul in last three months.
Adherence with medications
No active infection
No active malignancy
No history of cryptospordia or lymphoma
HIV RNA not detectable in last 6 months
Access to medications and ability for regular follow up
Standard pre transplant infection screen should be done and immunization protocols followed
As regards immune suppression , induction with Basiliximab and maintenance with TAC, MMF and steroids
Regular follow up and drug level monitoring
PCP prophylaxis will be required
CD 4 counts and HIV RNA should be monitored.
Criteria for transplantation: 1. a CD4+ count above 200 cells/µL of blood. 2. HIV-1 RNA viral load suppressed with treatment. 3. Stable cART regimen for over 6 months. 4. When there is HCV PCR positive is associated with higher all-cause mortality. 5. HCV viral genotyping. DAA therapies for the treatment of chronic HCV infection. 6. Exclude cirrhosis, LFTs, Ultrasound, Liver biopsy. 7. Evidence of current vaccine induced/natural immunity to diphtheria, tetanus and pertussis, measles, mumps and rubella, pneumococcus, hemophilus influenza, meningococcus B, influenza, VZV, hepatitis A and Hepatitis B. 8. Monitor for HIVAN recurrence post transplant.
· First, he needs a general assessment as a non-infected candidate.
· Next, he needs evaluation for the severity of liver disease and the presence of portal hypertension
· If he has compensated cirrhosis, and no portal hypertension he will go for isolated kidney transplantation, and if he has decompensated cirrhosis or clinically significant portal hypertension he will need a simultaneous liver–kidney transplantation.
· He should be given DAA therapy, either before or shortly after transplantation.
· If he has HIV RNA levels<200 copies/mL, he could be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications.
· He needs serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii.
· He should be tested for latent TB infection with an interferon-gamma test with or without a concurrent Mantoux test according to NICE Tuberculosis Guidelines.
· If he has a positive test for latent TB infection, he should be assessed and managed for any evidence of active TB disease.
· He should 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.
· Hepatitis B virus and Hepatitis A virus vaccines should be given to non-immune patients.
· Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients.
· Varicella zoster vaccine is given 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 given if he is nonimmune to measles.
· A dose-finding trial of CNI prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
· Pre-emptive switching from boosted protease-inhibitors (PI)-based antiretroviral regimens, if possible, to minimize drug interactions.
1) KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
2)Kidney & Pancreas Transplantation in Patients with HIV. British Transplantation Society Guidelines
This is a special scenario of coinfection with HIV and HCV
Involvement of hepatologist and ID specialist is early and continuous
In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused.
We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B)
in those with evidence of active HCV replication (1C)
recommendations that kidney and/or pancreas transplant candidates are treated for HCV prior to transplantation.
Pangenomic DAAT is required to treat HCV
HAART (if HAART naïve) – non-PI based regimens are preferred, aim to achieve CD4 >200, undetectable viral load prior to transplantation
As we prepare all recipients we need mdt including nephrologist,hepatologist and infectious
History and clinical examination
CBC KFT LFT PT PTT INR Coagulation profile
Albumin ,virology CMV ,EBV ,HCV,HBV PCR,HIV
Chest abdomen pelvic ct
Assessment for liver fibrosis and portal HTN
treatment with DAA
In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused.
We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
recommendations that kidney and/or pancreas transplant candidates are treated for HCV prior to transplantation.
HIV and HCV coinfection:
HIV positive infection: criteria prior transplantation which are: CD4+ count more than200 cells/µL of blood.
Treatment to suppress HIV-1 RNA viral load.
Stable cART regimen for over 6 months.
DAA for treatment of chronic HCV infection sustained virologic response 12 weeks after treatment.
PCR of HCV if highly infectious for treatment, and exclusion of liver cirrhosis by doing LFTs& Abdominal US.
Induction using Basiliximab .
Maintenance IS by TAC, Steroids, MMF.
References:
Saxena V, Khungar V, Verna EC, et al. Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: results from the HCV-TARGET study. Hepatology. 2017;66(4):1090-1101.
Reau N, Kwo PY, Rhee S, et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology. 2018;68(4):1298-1307
This sort of transplant need very close and special consideration ,like from HIV point of view:
the recepient is having both HIV and HCV.
Regarding HIV;
need to be on HAART therapy and achieved remission with HIV RNA undetectable for the last 6 month ,adding to that he has to be on non PI regiem base medication (not to interfer with IS). need to have CD4 count of more than 200 .
This patient with HIVAN need to be counselled regarding recurrence of the disease in the transpolanted kidney .
This patient condition with HIV need to be in good health with no OI in the last 6 month and no past hx of PML.
This patient should be counselled regarding his active HCV infection which is have a lot of implication on the treansplanted kidney .
This patient suppose to be on DAAT pre transplant, pangenomic regimen until we attain a virological response.
He need to be have normal liver with no sign of cirrhosis or sign of decompensated liver disease .
This patient need post RTX FOLLOW UP WITH THE FOLLOWING:
Lifelong PCP prophylaxis.Toxo,CMV and MAC prophylaxis to be considered.
Hep A, Pneumococcal, influenza, DPT,MMR and HPV vaccines to be given where applicable.
Induction with basiliximab,avoid ATG.
Maintenance with CNI/Steroids/Antimetabolites.
Regular HIV RNA and CD4 levels;1/12,2-3/12 in Year 1 then every 3-6/12.
6. A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. His HCV PCR is positive but HBsAg negative.
Issues/ concerns
– 41yo male, CKD on HD, HIVAN
– HCV PCR positive, HBsAg negative
Outline the workup required to prepare him for renal transplantation. (1, 2)
– it is prudent to carefully evaluate kidney transplant candidates in order to detect and treat coexisting illnesses which may negatively impact the transplant outcomes
– the evaluation determines whether the transplant is feasible and guides post-transplant immunosuppressive therapy
– the evaluation process should be as efficient and cost effective as possible
– preemptive transplantation is associated with improved patient and graft survival
etiology of kidney disease, any native kidney biopsy, helps assess the risk of recurrent disease after transplantation, also assess the current disease activity
medical comorbidities e.g., cardiovascular disease, cerebrovascular disease
– absolute contraindications: active malignancy (excluding NMSC), active infection, active substance use disorder, reversible kidney disease, documented active and ongoing treatment nonadherence, uncontrolled psychiatric illness, shortened life expectancy
– recipient age alone is not a contraindication to transplantation
– relative contraindications: malnutrition, primary oxalosis, systemic amyloidosis, active systemic diseases that may limit the longevity of the graft e.g., uncontrolled ANCA, SLE, MGUS, severe uncontrolled hyperparathyroidism
peptic ulcer disease, cholelithiasis, diseases of the colon or liver
hypercoagulable state (as suggested by history of arterial/ venous thrombosis, AV graft or fistula thrombosis, prior unexplained graft thrombosis, SLE)
MGUS
Bladder dysfunction, augmentation or substitution, recurrent UTI, pyelonephritis or reflux
– history of prior surgery especially abdominal surgeries
– drug history i.e., drugs metabolised by cytochrome P450 system can interact with the immunosuppressive agents
– immunization history
– physical activity (i.e., frequency, intensity, type of activity) to assess the patient’s functional status
– detailed physical examination including assessment of BMI and central adiposity, oral examination checking for dental decay, auscultation of carotid bruit, assessment of bilateral femoral and pedal pulses and lower extremity integrity, palpation for abdominal masses e.g., polycystic kidneys, assessment of prior abdominal procedures e.g., PD catheter insertion since this may affect placement of the graft kidney, dialysis access location
– psychosocial assessmentto identify behavioral, financial and social issues which may influence adherence and outcomes post-transplant
– the patient must understand the potential risks and benefits of transplantation, the need for lifelong immunosuppressive agents, need for adherence to medication and follow-up
– the patient should be able to give informed consent for transplantation
– patients with psychiatric disorders e.g., mood, anxiety, personality disorders need psychiatric assessment in order to improve access to and success following transplantation
– alcohol and substance use disorders must be addressed prior to transplantation
– assess patient’s prior and current adherence to medications, clinics, dialysis sessions
– patient should have a social support system in place throughout the transplant process
– the patient’s financial status should be assessed and any barriers addressed before transplantation
imaging – chest radiograph, abdominopelvic ultrasound, fibroscan to assess for liver fibrosis
cardiac assessment – ECG, ECHO
cancer screening – colonoscopy
urologic abnormalities e.g., bladder dysfunction, bladder augmentation or substitution
– holistic management:
– initiate on HAART (if HAART naïve) – non-PI based regimens are preferred, aim to achieve CD4 >200, undetectable viral load prior to transplantation
– initiate pangenotypic DAA therapy as definitive treatment for the HCV infection – aim for SVR
– treat any other detectable opportunistic infections and offer lifelong prophylaxis
– vaccines preferably given prior to the transplant
– induction therapy – basiliximab is preferred
– maintenance therapy – use a triple regimen (CNI, antimetabolite, corticosteroids)
– monitor CD4 and viral load closely in the immediate post-transplant period
References
1. Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020 Apr;104(4S1 Suppl 1):S11-S103. PubMed PMID: 32301874. Epub 2020/04/18. eng.
2. Knoll G, Cockfield S, Blydt-Hansen T, Baran D, Kiberd B, Landsberg D, et al. Canadian Society of Transplantation consensus guidelines on eligibility for kidney transplantation. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne. 2005 Nov 8;173(10):1181-4. PubMed PMID: 16275969. Pubmed Central PMCID: PMC1277045. Epub 2005/11/09. eng.
3. Bunnapradist S, Danovitch GM. Evaluation of adult kidney transplant candidates. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2007 Nov;50(5):890-8. PubMed PMID: 17954303. Epub 2007/10/24. eng.
A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. His HCV PCR is positive but HBsAg negative. Hep C and HIV co infection management in kidney transplantation.
Both conditions can be virally suppressed by treatment and thus transplant should proceed with careful preparation.
HIV specific evaluation;
CD4
VL
HLAB5701.
HIV resistance profile.
Ca screen -Cervical and Anal Ca.
Co infection screen -HBsAG and HBV RNA.
OI investigations;
CMV IgG,IgM
Toxo IgG,IgM
Urine LAM/mantoux/Igra
serum crag
VDRL
HSV PCR
HTLV1 and 2 Elisa
HCV specific evaluation;
HCV PCR.
LFTS to assess for any hepatitis.
Fibro scan to assess for liver cirrhosis .
Assess for portal HTN and other complications of liver cirrhosis.
Management;
HIV;
Start HAART and establish compliance, use a non PI based regimen and aim for CD4 counts > 100 for atleast 3/12 or undetectable HIV RNA in past 6/12.
Any LTBI or active TB to be tx using NICE guidelines.
Ensure good hx with no OI in past 6/12 or past PML, Cryptosporidiosis or lymphoma.
HCV;
DAAT pre transplant, pangenomic regimen until we attain a virological response.
Other Mgt;
Lifelong PCP prophylaxis.Toxo,CMV and MAC prophylaxis to be considered.
Hep A, Pneumococcal, influenza, DPT,MMR and HPV vaccines to be given where applicable.
Induction with basiliximab,avoid ATG.
Maintenance with CNI/Steroids/Antimetabolites.
Monitor for DI.
Regular HIV RNA and CD4 levels;1/12,2-3/12 in Year 1 then every 3-6/12.
Other post op care as in non HIV popn.
REF;
BTS Guidelines -Kidney and Pancreas Transplantation in Pts with HIV.
Outline the workup required to prepare him for renal transplantation. The first step will be detailed counselling regarding the pros and cons. Criteria for transplantation include – No history of opportunistic infections No active cirrhosis and active HCV replication CD 4 count more than 200 copies/Ul in last three months. Adherence with medications No active infection No active malignancy No history of cryptospordia or lymphoma HIV RNA not detectable in last 6 months Access to medications and ability for regular follow up Standard pre transplant infection screen should be done and immunization protocols followed
As regards immune suppression , induction with Basiliximab and maintenance with TAC, MMF and steroids
Regular follow up and drug level monitoring PCP prophylaxis will be required CD 4 counts and HIV RNA should be monitored.
Outline the workup required to prepare him for renal transplantation.
41year old with CKD secondary to HIVAN, HCV PCR positive HBsAg negative.
Kidney transplantation is associated with better survival rates in HIV positive patients than remaining on dialysis. Hence this patient first needs to be counselled on the pros and cons of transplantation.
This patient has HCV co-infection hence it’s crucial to rule out liver cirrhosis and fibrosis prior to transplantation.
This can be done using U/S and AST to platelet index ratio (APRI). Scores >0.8 and suggestive U/S requires referral to liver specialist.
The absence of liver cirrhosis and fibrosis the patient can be initiated on DAA as awaits kidney transplantation. HCV genotyping should be done to determine the DAA.
If the patient has liver cirrhosis then patient should be referred for combined liver pancreas transplantation.
This patient is known HIV positive with HIVAN though not indicated the patient should be on cART. Some classes of cART are associated with metabolic syndrome and diabetes mellitus. Thus this patient should be screened for diabetes mellitus and if diabetic should be considered for simultaneous pancreas-kidney transplantation.
Other Workups should include:
CD4 counts and HIV RNA
Should have undetectable HIV RNA for 6 months with CD4 counts above 200cells/ul for 3 months.
Should also be adherent on cART.
Should have no prior history of virological failure.
Testing for HLA-B5701 should be done.
Recipient should have no opportunistic infections/active malignancy.
Screening for opportunistic infections should include a detailed history and workups.
TB- screening for latent TB should be done with IGRA and patients who are positive should be screened for active TB.
Patient with history of recent exposure to persons with TB should also be screened for active TB.
CMV- serological testing prior to transplantation.
KS-patient should have no prior history of treatment for kaposi sarcoma.
Should also have no prior history of PML, lymphoma and intestinal cryptosporidiasis.
In endemic ares recipient should also be screened for strongyloides stercolaris.
Serological screening for syphillis, EBV, HCV, toxoplasma gondii, HSV, HTLV1 should be done.
Recipient should receive immunisation.
Non-immunised recipients should receive HBV,HAV and VZV vaccine.
Annual influenza vaccine should be given while on the waiting list.
Recipient should be suggested to receive DTP vaccine and those who received more than 10 years ago should get a boaster.
Recipient should receive pneumococcal vaccine (PPV23) and repeated every 3-5years.
Recipients with high risk should receive HPV vaccine.
Non-immunised patients should be suggested to receive MMR vaccine.
Other considerations
Recipient should have their ART reviewed and switched to drugs with minimal drug interactions.
Nephrotoxic ART should be avoided.
The induction therapy should be with IL2RA and lymphocyte depleting agents avoided.
Maintenance should be triple immunotherapy with CNI/mycophenolate/steroids.
References
Kidney & Pancreas Transplantation in Patients with HIV Second Edition Compiled by a Working Party of The British Transplantation Society March 2015[Minor Revision January 2017]
British Transplantation Society Guidelines
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
-counseling regarding the pros & cons of transplantation
-detailed hx focusing on drug failure, hx of opportunistic infections , lymphoma or PML & TB.
– should meet the following criteria:
1.HIV RNA has been undetectable or <50 copies for the last 6 months.
2.no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
3.no hx of opportunistic infection
4. assessment for HCV co-infection; should be no liver cirrhosis or HCV active viral replication.
5. CD4+ cell count > 200 cells/µl during 3 months prior to transplantation
6. Documented adherence with stable antiretroviral treatment regimen
7.Absence of active opportunistic infection and malignancy
8.Access to immunosuppressive agent therapeutic drug monitoring
9. Ability to regularly follow up with HIV care providers
When it comes to a kidney transplant, the vaccination protocol must be followed to the letter and at the right time.
-pre-transplant immunization, annual influenza vaccine & HVP vaccine if risky for HPV acquisition
-induction with basiliximab & maintenance with steroid+tacrolimus+MMF
-good attention & monitoring of drug-drug interactions
-lifelong prophylaxis against Pneumocystis pneumonia
– HIV RNA and CD4+ T-cell counts are monitored regularly, 1 month after transplant and subsequent every 2-3 months for the first year then every 3-6 months .
A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. He is HCV positive but HBsAg negative.
Outline the workup required to prepare him for renal transplantation? Kidney transplantation is recommended as the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection (1A).
I will first evaluate this patient for severity of liver disease & presence of portal hypertension before accepting him for Kidney transplant.
If the workup revealed compensated liver cirrhosis (without portal hypertension), I will accept him for isolated Kidney transplant and consider for DAA therapy, either before or after transplant (1A). (KDIGO HCV Guideline Recommendation 4.1.3.1)
If there is decompensated cirrhosis, I will refer him for combined liver-kidney transplantation & defer HCV treatment until after transplantation.
HIV/HCV confection is associated with increased mortality, there is controversy about the risk of liver disease progression with immunosuppression and the development of HCV transplant glomerulopathy as higher rates of progression to cirrhosis are detected in patients with HCV/HIV
A transplant infectious disease specialist needs to review HIV and ART history, vaccinations, and tuberculosis risk factors, also with HCV confection, hepatologist assessment is needed along with evaluation of degree of liver fibrosis, often via transient elastography or biopsy as needed.
Wait periods for an HCV-infected organ need to be monitored, and transplant hospitals need to frequently evaluate the danger of postponing HCV antiviral treatment. Transplant candidates who are HIV/HCV coinfected require a comprehensive strategy with a focus on cardiovascular risk profileand a low threshold for cardiac catheterization. Other factors to consider in timing (before versus after) of HCV treatment in relation to KTX include: 1. Donor type (living vs. deceased)
2. Waitlist times by donor type
3. Center-specific policies governing the use of kidneys from HCV-infected deceased donors
5. HCV genotype needs to be known and the patient started on appropriate directly acting antiviral agent started to achieve SVR prior to transplant
6. Severity of liver fibrosis
7. If the patient in this scenario has a suitable living donor, I will consider for treatment before or after TX according to HCV genotype & anticipated timing of transplant.
8. Need to assess for cirrhosis – if patient has cirrhosis, then it is a relative contraindication to transplantation in an HIV positive patient. Regarding HIVAN in this scenario, I will consider the following:
His HIV per se is not a contraindication for Kidney transplant; however, he will be wait-listed only if:
He is concordant with treatment (combined ART therapy)
His CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) & have been stable during the previous 3 months.
HIV RNA has been undetectable during the previous 6 months.
No opportunistic infections during the previous 6 months
No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
The most appropriate ART therapy is determined before TX after discussion with an HIV specialist to anticipate potential drug interactions and appropriate dosing of medication. Absolute contraindications to kidney transplantation in patients with HIV:
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)
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 PM.
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer.
g) Pregnancy. 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) Other workup components include:
Those testing positive for latent MBTB are assessed for any evidence of active TB disease.
Those with evidence of active TB disease are treated according to current NICE guidance prior to transplant.
Latent MBTB is treated according to current NICE TB guidelines, prior to transplantation.
Transplant candidates from endemic regions are screened for Strongyloidiasis stercoralis infection prior to transplant.
ARTs with nephrotoxic potential (tenofovir & atazanavir) are avoided if suitable alternatives are available.
ART with significant drug-drug interactions with CNIs (ritonavir & cobicistat) are avoided if suitable alternatives are available. Reference:
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017]
Successful Kidney Transplantation in a Recipient Coinfected with Hepatitis C Genotype 2 and HIV from a Donor Infected with Hepatitis C Genotype 1 in the Direct-Acting Antiviral Era Received 23 September 2019; Accepted 3 January 2020; Published 30 January 2020
Mazumder S A. Treatment Recommendations for HIV-Infected Patients with Co-infections. Medscape 2022
Sawinski D. Kidney Transplantation in Patients with HIV. Kidney360. 2020;1(7):705-711. Published 2020 May 6.
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Transplant Candidate Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104: S1–S103.
Evidence of current vaccine induced/natural immunity to diphtheria, tetanus and pertussis, measles, mumps and rubella, pneumococcus, hemophilus influenza, meningococcus B, influenza, VZV, hepatitis A and Hepatitis B, HPV vaccine is offered to patients at risk of HPV acquisition.
Those from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation.
CD4 cell count, HIV RNA level, current and prior antiretroviral therapies and HIV resistance profile.
Serologic testing for syphilis, HSV, EBV, CMV, VZV, human T cell leukemia virus and toxoplasma gondii.
Liver function tests, ultrasound, check for liver cirrhosis and consult with liver specialist.
Crucial to watch for HIVAN recurrence post transplant.
References
Ahmed Halawa. HV and kidney transplantation. University of Liverpool, UK. 2023.
Outline the workup required to prepare him for renal transplantation
HIV positive infection is not contraindication for transplantation but there criteria befor transplantation which are: a CD4+ count above 200 cells/µL of blood.
HIV-1 RNA viral load suppressed with treatment.
Demonstrable concordance to a stable cART regimen for over 6 months.
When there is HCV PCR positive HCV seropositivity is associated with higher all-cause mortality.
DAA therapies for the treatment of chronic HCV infection has been introduced, with cure rates defined as sustained virologic response 12 weeks after treatment of greater than 98%.
We need to PCR of HCV if highly infectious for treatment first ,and we need to exclude liver cirrhosis by doing LFT ,Abd US .
The induction by Basiliximab .
The maintenance by TAC,Steroids, MMF . References
1.. Saxena V, Khungar V, Verna EC, et al. Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: results from the HCV-TARGET study. Hepatology. 2017;66(4):1090-1101.
2. Reau N, Kwo PY, Rhee S, et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology. 2018;68(4):1298-1307
Patient with HIV and HCV positive should counselling regarding reactivation post transplant
In HIV should be met Criteria of CD4T cell count more than 200 micro/ ml and Viral load less than 50 copies/ ml and no evidence of opportunities infection and malignancy for all 3 months at least and should be adherence to highly antiretroviral therapy
For HCV infection should be do HCV PCR, if high should be treated with direct antiviral therapy prior to transplant and do LFT and ultrasound to role out liver cirrhosis
During transplant should start immunosuppressive therapy consist of basiliximab as induction therapy and maintenance therapy is tacrolimus/ steroid/ MMF.
HIV/HCV co-infection in potential kidney transplant recipients can be very challanging case to manage.
Following work up may be considered on priority apart from routine transplant work up
FOR HIV INFECTION
CD4+ T cell count more that 200 cells/microlit persistantly for last 3 months
Undetectable / suppressed (50 copies/ml) HIV viremia persistantly for last 6 months
No history of any opportunistic infection in last 6 months
PML, lymphoma and malignancies (cervical/anal neoplaia, castelaman disease)
FOR HCV INFECTION
Assessment of active viral replication (absolute contransdication)
evaluation for liver chirrhosis (if present then absolute contransdication)
Viral genotyping
REF:
BTS guidelines
Y. Xia 1 2, P. Friedmann 2, H. Yaffe 1 2, J. Phair 2, A. Gupta 3, L.K. Kayler. Effect of HCV, HIV and Coinfection in Kidney Transplant Recipients: Mate Kidney Analyses.American Journal of TransplantationVolume 14, Issue 9, September 2014, Pages 2037-2047
Outline the workup required to prepare him for renal transplantation.
HIV/HCV co-infected patients have worse outcomes than their mono-infected counterparts in post kidney transplantation which should be discussed with the patient .
Patients with HCV/ HIV co-infection should meet the prerequisites for each of them before kidney transplantation.
For HIV infection :
CD4+ cell count > 200 cells/µl during 3 months prior to transplantation with undetectable plasma HIV viremia , adherence with stable antiretroviral treatment ,absence of active opportunistic infection and malignancy, access to immunosuppressive agent therapeutic drug monitoring .
HCV infection :
With positive HCV PCR , proceed to genotyping and assessment of liver function and degree of fibrosis with start of DAA accordingly .
Patients with extensive fibrosis may require simultaneous liver and kidney transplant .
Following viral load and drug monitoring after transplantation is mandatory .
*Check TB status and manage accordingly ,latent or active TB should be treated before transplantation .
* Vaccination : HBV, HAV, pneumococcus, VZV, influenza HPV, DPT and MMR vaccines where applicable.
* Prophylaxis against opportunistic infections like CMV &PCP.
* Immunosuppressive treatment : induction preferred with IL2 receptors antagonist with avoidance of lymphocyte depleting agents .
* Monitoring drug level and follow for drug interactions.
Reference:
Living kidney donation in individuals with hepatitis C and HIV infection: rationale and emerging evidenceCurrent Transplantation Reports, 30 Apr 2019, 6(2):167-176 DOI:10.1007/s40472-019-00242-5 .
Hepatitis C Virus Treatment and Solid Organ Transplantation .Gastroenterology & Hepatology Volume 18, Issue 2 February 2022.
Plan of management is to 1.To look for any absolute and relative contraindication for transplant.
2.Treat Hepatitis C infection before transplant i.e to have sustained viral response.
3.Treat HIV with cART before transplantation for prerequisite criteria i.e havingundetectable HIV RNA for last 6 months, CD4 count >100/microL (ideally >200/microL) for more than 3 months, absence of opportunistic infection in last 6 months, and no history of lymphoma, cryptosporidiosis, and progressive multifocal leukoencephalopathy (PML).
Through history and examination: standard work up for recipient
HIV viral load, CD4 count.
Screening for infection
MDT with liver specialist and infectious disease
HCV antibodies, HCV RNA PCR, Liver function tests, ultrasound abdomen, and portal hypertension (upper gastrointestinal endoscopy).
Standard Pre-transplant immunization.
Flow crossmatch -negative
ART medication review should be done, to avoid nephrotoxic drugs, and drugs with potential interactions with immunosuppressives post-transplant.
A dose-finding trial of calcineurin inhibitors (Tacrolimus) can be done if the patient is wait-listed.
Induction:It should be offered with Basiliximab
Maintenance immunosuppression:Tacrolimus, MMF and steroids.
Post-transplant prophylaxis would include pneumocystis (lifelong), cytomegalovirus (minimum 3 months), toxoplasma (lifelong in seropositive recipients with CD4 <200), mycobacterium avium, treatment of latent tuberculosis if positive
Post-transplant monitoring of HCV RNA, HIV RNA, LFT, and CD4 count (at 1 month and then every 2-3 months for 1 year and then 3-6 monthly) in addition to the standard followed in all transplant recipients.
Watch for drug resistance.
Watch for HIVAN recurrence
References
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV
Thank you, Prof for the question.
Yes, we can predict resistance in such a patient as acquired HIVDR occurs when mutations develop to drugs in individuals who have received ARV if there is a) poor adherence b) treatment interruptions c) inadequate drug concentrations, d) use of sub-optimal drug or combination of any.
WHO recommends 3 survey methods to monitor the prevalence of acquired HIV drug resistance:
nationally representative clinic-based method; and
sentinel laboratory-based method.
Both nationally representative methods generate estimates of acquired HIV drug resistance among people with viral non-suppression (≥1000 copies/ml) taking dolutegravir-containing and non-dolutegravir-containing ART. The sentinel method focuses on HIV resistance to dolutegravir among individuals receiving dolutegravir-containing ART with confirmed viral non-suppression.
References Nachega JB, Marconi VC, van Zyl GU, Gardner EM, Preiser W, Hong SY, Mills EJ, Gross R. HIV treatment adherence, drug resistance, virologic failure: evolving concepts. Infect Disord Drug Targets. 2011 Apr;11(2):167-74. doi: 10.2174/187152611795589663. PMID: 21406048; PMCID: PMC5072419.
A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) . His HCV PCR is positive but HBsAg negative. Outline the workup required to prepare him for renal transplantation.
It is accepted for our case to proceed for kidney transplantation but we should explain worse outcome of graft survival with coinfection with HIV and HCV, no special consideration should be taken. Recipient with HIV should fulfill these criteria:
a) patients who 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 . Pre-transplant immunization
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titers <10 mIU/mL).
• Hepatitis A virus (HAV) vaccine, 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), (MMR) vaccine is administered to all patients (2D) Immunosuppression:
Induction therapy is with an interleukin-2 receptor antagonist (IL-2RA), preferred than ATG, with triple tacrolimus based therapy and bear in mind the drug-drug interaction . Post-transplant prophylaxis
• Life-long 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.
• 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 . HCV work up:
Long-term outcome of HCVR+ transplanted with kidneys from HCVD+ seems good in terms of patient survival, graft survival and liver disease and HCVD+ was not a significant risk factor for mortality, graft failure and liver disease among HCVR+. Recipient should have compensated cirrhosis, or early fibrosis with absence of portal hypertension, will go ahead to transplant and then treat with DAA after the surgery for 12 weeks according to the genotype with strict follow up. However, if there is decompensated cirrhosis and portal HTN > 10mmHg with hepatologist assessment, will look for simultaneous liver and kidney transplantation and then treat the recipient with DAA after the surgery.
Close follow-up of patients with careful monitoring for early detection of post-transplant liver complications might have been decisive. References:
1.British Transplantation Society. Kidney and Pancreas Transplantation in patients with HIV.
2.Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688. 3-(KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS 4- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS).
Outline the workup required to prepare him for renal transplantation.
The index patient is an ESRD patient on hemodialysis with basic disease of HIVAN (HIV associated nephropathy) with co-infection in form of HCV positivity, while HBsAg is negative.
The patient can be taken up for a kidney transplant if certain conditions are met (1). These include being concordant with cART treatment, having undetectable HIV RNA for last 6 months, CD4 count >100/microL (ideally >200/microL) for more than 3 months, absence of opportunistic infection in last 6 months, and no history of lymphoma, cryptosporidiosis, and progressive multifocal leukoencephalopathy (PML).
Presence of pregnancy, active malignancy, serious ongoing infection, multi-drug resistant HIV infection, a positive CDC crossmatch, substance abuse, major psychiatric illness, and CD4 <100 with persistently detectable HIV RNA in previous 3 months are absolutecontraindications for kidney transplant. Relative contraindications include a positive flowcytometry cross match, ABO incompatibility, treated malignancy, uncontrolled medical problems, chronic liver disease, HTLV infection, and BMI >35 (1).
Pre-transplant assessment: It would, in addition to the standard work-up for a transplant recipient, include detailed history (including treatment history), physical examination, HIV viral load, CD4 count, as well as 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 (1).
Pre-transplant immunization with HBV vaccine, Hepatitis A vaccine, pneumococcal vaccine, varicella zoster vaccine, and influenza vaccine is recommended. In addition vaccination with DTP, MMR and HPV vaccine is also suggested (1).
cART medication review should be done, to avoid nephrotoxic drugs, and drugs with potential interactions with immunosuppressives post-transplant.
Recipient evaluation with respect to HCV status: The recipient should be evaluated with respect to positive HCV status – anti-HCV antibodies, HCV RNA PCR, Hepatitis B virus infection assessment (HBsAg is negative in the index patient), hepatology consultation, Liver function tests, ultrasound abdomen, and assessment of liver fibrosis (elastography, liver biopsy) and portal hypertension (upper gastrointestinal endoscopy). In presence of advanced liver fibrosis, a combined liver and kidney transplant would be required (2,3).
Active HCV replication is a contraindication for transplantation according to the BTS guidelines due to increased mortality seen with HCV/HIV co-infection (1). Patient can be considered for renal transplantation only if there is plan to treat HCV infection using DAAs either pre-transplant, or in early post-transplant period (2).
Use of HCV positive organ followed by post-transplant DAA therapy can increase the pool of organs available (4). So, if there is a possibility of receiving a kidney in next 24 weeks, treatment with DAAs can be withheld till transplant, and should be started in early post-transplant period (3).
The recipient can be eligible for both HIV positive donor (with HIV viral load <50 copies/ml and CD4>200 for at least 6 months and no history of virological failure or drug resistance) as well as HCV positive donors, thereby increasing the donor pool for him.
A dose-finding trial of calcineurin inhibitors (Tacrolimus) can be done if the patient is wait-listed for cadaveric donor (1,5).
Induction: It should be offered, with Basiliximab in majority.
Maintenance immunosuppression: Tacrolimus, MMF and steroids.
Post-transplant prophylaxis would include pneumocystis (lifelong), cytomegalovirus (minimum 3 months), toxoplasma (lifelong in seropositive recipients with CD4 <200). Post-transplant monitoring of HCV RNA, LFT, HIV RNA and CD4 count (at 1 month and then every 2-3 months for 1 year and then 3-6 monthly) in addition to the standard followed in all transplant recipients. Drug resistance testing may be required in case of persistent viremia.
Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688.
Martin P, Awan AA, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, Jia J, Kamar N, Mohamed R, Pessôa MG, Pol S, Sise ME, Balk EM, Gordon CE, Adam G, Cheung M, Earley A, Jadoul M. Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6):1228-1237. doi: 10.1016/j.kint.2022.07.012. PMID: 36411019.
Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. doi: 10.1097/QAD.0000000000002518. PMID: 32167973.
Pulzer A, Seybold U, Schönermarck U, Stangl M, Habicht A, Bogner JR, Franke J, Fischereder M. Calcineurin inhibitor dose-finding before kidney transplantation in HIV patients. Transpl Int. 2013 Mar;26(3):254-8. doi: 10.1111/tri.12020. Epub 2012 Dec 10. PMID: 23227980.
You state that the prophylaxis duration for pneumocystis (lifelong) and for toxoplasma (lifelong in seropositive recipients with CD4 <200). Do you have separate drugs for these 2?
Co-trimoxazole can be used as prophylaxis for both pneumocystis as well as toxoplasmosis. The difference lies in the dosage recommended. For pneumocystis, the dose recommended is 480 mg daily, while for toxoplasmosis, the dose is 960 mg daily.
Recipient preparation would start by proper counselling with details concerning both advantages and disadvantages (increased susceptibility to opportunistic infections, rejection episodes, recurrence of HIVAN, increased viral replication of HCV and HIV).
Detailed history taking is a must regarding; dialytic complications, blood transfusions, opportunistic infections, history suggestive of PML, history of symptoms suggestive of TB , other comorbid diseases as DM ,HTN ,obesity and smoking.History suggesting malignancies and lymphomas must be excluded.
Vaccination protocol must be fully applied within proper timing in relation to renal transplantation.
Being HCV positive is known to a common co-infection in PWLHIV. Hepatology consultation is crucial to assess HCV load, liver enzymes, and hepatic tissue status after performing fibroscan as well to be able to tailor the best treatment protocol for this patient and exclude the need of simultaneous liver kidney transplantation.
Regarding HIV ,it is mandatory to check proper patient adherence to c ART therapy ,undetectable levels of HIV RNA is a must along with ideal CD4 count ( from 100 to 200 cells /ul is advised not to be less ).
Ensure the availability of insurance to allocate both antiviral medications for HIV and HCV.
Full examination for the patient in multisystem approach as cardiac and chest as well as other body systems to assess fitness for renal transplantation operation.
Routine tests would be besides other expected viral infections as EBV, TB quantiferon tests, HSV, Toxoplasma and other suspected or endemic diseases.
The better the matching, the better results that can be achieved with less doses of immunosuppression.
Immunosuppression is advised to be triple regimen tacrolimus based with the best prophylaxis to be extended for long term especially for CMV and PCP.
I like you emphasis on adherence to medications in a transplant patient with HIV. Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Immune deficiency is a risk for liver fibrosis and organ insufficiency in patients co-infected with HCV in case of active viral replication. For that reason, the recommendation is against kidney and or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C).
In our scenario, we need to ensure a negative viral load for both HIV &HCV. The patient should also be on cART, clinically stable, without opportunistic infection history for at least the last six months. For his patient, it is wise to give direct antiviral treatment against HCV before transplantation. We need to make sure about the absence of cirrhosis. From this aspect, in addition to routine work-up done for transplant candidates (CBC, biochemistry, viral serology, Abdominal ultrasound etc.), we need consultation and evaluation by gastroenterologists and infectious diseases experienced. We need to check for portal hypertension by doppler and gastroscopy.
We can see diverse lesions in HIV patients. Some of the pathologic findings may be related to the virus itself, while others can be related to the viral gene expression, drug effects or associated infections.
HIV-related kidney disease can be: Gleomuralar dominant or tubulointerstitial dominant A- Golemurular dominant:
1-podocytopathy (classic HIVAN, FSGS, MCD in the setting of HIV) or can present with mesangial hypercellularity
2- Immune complex-mediated glomerular disease:
Like HIV-negative patients, we can see IgA, Lupus-like, Lupsp nephritis, MPGD or membranous nephropathy.
B- Tubulointerstitial dominant
It can be an acute or chronic tubular injury.
C: dominant vascular injury: TMA in the setting of HIV o arteriosclerosis can be seen
**** Of note, the classic HIVAN was prevalent in the era that preceded ART therapy.
HIVAN pathology was described as collapsing glomerulopathy with interstitial disease, tubular microcysts, and interstitial lymphoplasmacytic inflammation. Diffuse podocyte foot process effacement is also a classic feature.
Clinically, proteinuria in a nephrotic range can be typically seen. Although a biopsy is the gold standard, screening is For that reason, the evaluation of the risk/screening should be done by evaluation for proteinuria, which is classically in nephrotic range.
** In the south African program, 12 patients out of 51 (10 years follow-up; 150 biopsies for clinical indications) were found to have HIVAN
** Workup should include CD4+ cell count, USG, urinalysis and p/cr ratio.
—————————–
1- Waheed, S., Sakr, A., Chheda, N. D., Lucas, G. M., Estrella, M., Fine, D. M., & Atta, M. G. (2015). Outcomes of renal transplantation in HIV-1 associated nephropathy. PLoS One, 10(6), e0129702.
2- Muller, E., Botha, F. C., Barday, Z. A., Manning, K., Chin-Hong, P., & Stock, P. (2021). Kidney transplantation in HIV positive patients: current practice and management strategies. Transplantation, 105(7), 1492.
Thank you, Prof. Ajay Sharma; I found different numbers, and the studies are mostly retrospective. So I could not find an approximate risk ratio to write exactly (Till moment; I will search again)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and co-infection with HCV, and corresponding mode of treatment indicated.
Workup of KT for HIV positive patient co-infected with HCV(1,2,3)
1. History and clinical examination to rule out opportunistic infection, complications like PML, liver cirrhosis and malignancy. History related to compliance with cART and response to treatment.
2. CD4+ cell count ,HIV RNA and HCV RNA to rule out active viral replication.
3. The transplant recipient should meet the following criteria:
a) HIV RNA has been undetectable during the previous 6 months.
b) No opportunistic infections have occurred during the previous 6 months.
c) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
d) Regarding HCV co-infection; there should be no liver cirrhosis nor HCV active viral replication.
4. Screening for viral hepatitis HBV, HDV and HEV.
5. Screening for other infections; CMV, EBV, HSV, VZV, HTLV, TB, Toxoplasma, Strongyloides stercoralis.
6. To rule out liver cirrhosis and HCC. If present, dual liver and kidney transplant to be considered.
7. DAA for HCV before transplantation.
8. cART for HIV to keep the viral load undetectable.
9. Pre-transplant immunization: for HBV, HAV, VZV, DTP, HPV, MMR, influenza and pneumococcal vaccines.
10.Post-transplant prophylaxis:
a) lifelong prophylaxis against Pneumocystis pneumonia following transplantation.
b) lifelong 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.
c) CMV prophylaxis for a minimum of 3 months for seronegative recipients of organs from CMV seropositive donors.
d) TB prophylaxis when TB exposure is suspected.
e) Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/μL, and to be stopped when the CD4 count is >100 cells/μL for 6 months.
11.A full and current medication review looking for drug-drug interaction.
12.Induction therapy with IL-2RA(Basiliximab).
13.Maintenance IS; the triple of CNIs, MMF and prednisolone. mTORi have an anti-HIV effect.
14.Acute rejection is treated in HIV-positive kidney transplant in the same way as HIV-negative kidney transplant recipients.
References
1. Kidney & Pancreas Transplantation in Patients with HIV Second Edition Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017]
2. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org 3. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
HIV specialists and transplant teams should optimize ART therapy to minimize pre-Tx toxicity and post-Tx drug interaction.
Careful immuno-virological and AR status review (CD4 cell count, HIV RNA, Current or prior ART, HLA-B5701 status, and HIV resistance profile.
HIV RNA < 200 copies/mL is suitable for SOT if otherwise well and adherent to treatment.
Serological test for syphilis, HSV, EBV, CMV, VZV, T-cell leukemia, and toxoplasma gondii.
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.
A positive test for M.TB should be assessed for evidence of active TB.
Evident active or latent TB patients should be treated according to the NICE guidelines prior to Tx.
Those with positive HB or HC infection should have HB DNA or HC RNA and the presence of cirrhosis.
HBsAg +ve should receive HB treatment to ensure the DNA level is fully suppressed.
Donor virology screening and PCR.
Liver function and ultrasound to detect the presence or absence of liver cirrhosis.
ART prior to transplantation, until the viral load is not detected.
For HCV a) Undetectable viral load. b) Known compliance with ART. c) No active opportunistic infections. d) No associated malignancy. e) Feasibility to follow up. f) CD4 cell counts >/200 cells/microL, unless in the liver transplant which is >/100 cells/microL.
HCV is not considered as an exclusion of Tx with the availability of DAA.
Low BMI is recommended for combined liver-kidney Tx and HCV+ donor organs.
References
BTS guidelines
Belga S, Doucette KE. Hepatitis C in non-hepatic solid organ transplant candidates and recipients: a new horizon. World J Gastroenterol. 2016;22(4):1650-1663. 2. Kwong AJ, Kim WR, Lake JR, et al. OPTN/SRTR 2019 annual data report: liver. Am J Transplant. 2021;21(suppl 2):208-315. 3. Health Resources & Services Administration. Organ donation statistics. https:// http://www.organdonor.gov/learn/organ-donation-statistics/detailed-description#fig
Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 2014; 384:241–248. 2. Feinstein MJ, Bahiru E, Achenbach C, Longenecker CT, Hsue P, So-Armah K, et al. Patterns of cardiovascular mortality for HIV-infected adults in the United States: 1999 to 2013. Am J Cardiol 2016; 117:214–220. 3. Morse CG, McLaughlin M, Matthews L, Proschan M, T
⭐ HIV per se is not contraindication for Transplantation.
⭐ HCV infection is not CI to transplant ion in presence of DAAV.
👌 👌 However, coexistence of HCV and HIV can worsen the graft and patient outcome. _accepting transplantation can be done only if HIV prerequisites as (negative PCR, cd4 > 200 cells /ml, no active opportunistic infection , adherent to ART).
👉 plus HCV prerequisites as:
_HCV cure by DAAV prior to transplantation and achieving SVR.
_in addition, exclusion of fibrosis /cirrhosis by US, fibroscan and or biopsy is essential before consideration for Tx.
Workup for this transplantation: Need to evaluate general assessment then HIV and HCV co-infection status. As HCV is potentially treatable condition, need to treat prior to transplant.
Evaluation for HIV:
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.
Test for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii, latent Mycobacterium tuberculosis.
Screened for viral hepatitis.
Evaluation for HCV:
Need to exclude cirrhosis
Need to exclude active HCV replication
General management:
Immunization against HBV, HAV, pneumococcus, VZV, influenza HPV, DPT and MMR where are applicable.
Post transplant prophylaxis against pneumocystis and CMV.
Induction preferably by interleukin-2 receptor antagonist (IL-2RA)
Maintenance by triple immunosuppression.
Monitor for drug interaction between antivirals and immunosuppressives.
HIV management:
cART therapy.
CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and stable during the previous 3 months
HIV RNA undetectable during the previous 6 months
No opportunistic infections have occurred during the previous 6 months
HCV management:
DAA therapy prior transplantation.
References: – BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV – BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis,
6. A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. His HCV PCR is positive but HBsAg negative.
=================================================================== Outline the workup required to prepare him for renal transplantation.
Wait periods for an HCV-infected organ need to be monitored, and transplant hospitals need to frequently evaluate the danger of postponing HCV antiviral treatment.
Transplant candidates who are HIV/HCV coinfected require a comprehensive strategy with a focus on cardiovascular risk profile and a low threshold for cardiac catheterization.
Vaccinations, TB risk factors, HIV and ART history, and general and detailed assessments for HIV and HCV infections must all be reviewed by a transplant infectious disease specialist.
Gamma interferon test for latent TB, HCV RNA quantitative level and genotype testing, as well as serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus, and Toxoplasma gondii, are required.
Chronic hepatitis B or C or persistently abnormal liver function tests requirehepatologist evaluation, and transplantation is not advised in cases of ongoing HCV replication.
Workup for BMI, lipid profile, urine analysis, urinary Protein/CreatinineRatio, tumor screening, CD4 cell count, HIV RNA level, current and previous antiretroviral medications, HLA-B5701 status, and HIV resistance profile.
Making a safe and accurate diagnosis of hypersensitivity in patients carrying the HLA B 5701 allele is another step that is required to ascertain a drug’s effectiveness.
During the initial stages of anti-HCV PI introduction and termination, transplant hospitals should keep track of OPO-specific waiting times as well as tacrolimus levels.
The norm of care for transplant candidates who are HIV/HCV coinfected is pangenotypic DAA post-transplant.
Absolute contraindications to kidney transplantation in patients with HIV:
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)
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 PM.
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer .
g) Pregnancy.
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)
Management of DDI in patients infected with HIV and HCV is essential for improved outcomes with InSTI compared to PI after organ transplantation.
Coadministration of GLE/PIB with systemic tacrolimus (1 mg single dose) has been shown to increase Cmax and area under the curve (AUC) by 1.5-fold and 1.45-fold, respectively.
Improved liver function with anti-HCV treatment may further contribute to increased clearance.
In the setting of donor and recipient genotype strain mismatch, both viral strains may exist in the perioperative period.
The most important details are that long-term detection of both genotypes is possible, recommended regimens for the treatment of HCV in kidney transplant recipients, optimal timing of DAA treatment, risk of treatment delay and progression of liver disease, and benefit of shorter wait time for HCV-infected organs.
Treatment post-transplant was consistently cost-saving and associated with higher life-months and quality-adjusted life months with wait time.
J. E. Locke, R. D. Reed, S. G. Mehta et al., “Center-level experience and kidney transplant outcomes in HIV-infectedrecipients,” American Journal of Transplantation, vol. 15, no. 8, pp. 2096–2104, 2015
Successful Kidney Transplantation in a Recipient Coinfected with Hepatitis C Genotype 2 and HIV from a Donor Infected with Hepatitis C Genotype 1 in the Direct-Acting Antiviral EraReceived 23 September 2019; Accepted 3 January 2020; Published 30 January 2020
Sawinski D, Forde KA, Eddinger K, et al. Superior outcomes in HIV-positive kidney transplant patients compared with HCV-infected or HIV/HCV-coinfected recipients. Kidney Int. 2015;88(2):341-349. doi:10.1038/ki.2015.74
Platt L, Easterbrook P, Gower E, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016;16(7):797–808.
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of
The British Transplantation Society March 2015 [Minor Revision January 2017]
What is your reason for getting HLA B5701 allele, not that I am objecting to it.
Typing whole sentence in bold or typing in capitals amounts to shouting. Use of bullet points is not well done, at places you have used this along with (a) , (b) and (c) .
-HIV/HCV coinfection is associated with increased mortality, there is controversy about the risk of liver disease progression with immunosuppression and the development of HCV transplant glomerulopathy as higher rates of progression to cirrhosis are detected in patients with HCV/HIV
-A transplant infectious disease specialist need to review HIV and ART history, vaccinations, and tuberculosis risk factors, also with HCV coinfection , hepatologist assessment is needed along with evaluation of degree of liver fibrosis, often via transient elastography or biopsy as needed.
-General assessment have to be carried out as well as specific assessment for HIV and HCV infections
-The recipient has to be evaluated regarding the HIV RNA viral load and CD4-infected cell count , adherence and tolerance of ART ,history of ART resistance .
Also serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii are needed.
-Gamma interferon test for latent TB
-Assessment of HCV RNA quantitative level and genotype testing along with cirrhosis evaluation.
-screen for HB s Ag if positive HBV DNA level need to be done
-Cases with chronic hepatitis B or C or persistently abnormal liver function testing need to be evaluated by a hepatologist . if there is active hepatitis or cirrhosis then HBV or HCV will be considered as contraindication for renal transplant, otherwise cases with quiescent disease and a benign liver biopsy can proceed to kidney transplantation, meanwhile treatment can be required
-Assessment for the presence of cervical and/or anal neoplasia
-It is recommended to avoid transplantation in cases with active HCV replication ,extracutaneous Kaposi sarcoma, Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)-related lymphoma
-Treatment of HIV/HCV infection
Drug-induced liver injury (DILI) after ART is more common in HIV/HCV coinfection; eradication of HCV infection lower the risk of anti retrovirus-associated DILI.
LFT monitoring at 1 month then every 3 months after the initiation of ART.
ART is initiated as recommended in -naive patients. ART should be started at least 4-6 weeks before hepatitis C treatment is initiated.
Liver cirrhosis is evaluated according to the Child-Turcotte-Pugh classification system; hepatically metabolized antiretroviral drugs can be modified or avoided in patients with Child-Pugh class B and C
disease.
Treatment of both HCV and HIV can be complicated by drug interactions, drug toxicities, Many of the directly acting anti-HCV drugs have significant interactions with antiretroviral agents; however, ledipasvir with sofosbuvir and daclatasvir plus sofosbuvir have been efficient.
Reference
– Mazumder S A. Treatment Recommendations for HIV-Infected Patients With Co-infections .Medscape 2022
-Sawinski D. Kidney Transplantation in Patients with HIV. Kidney360. 2020;1(7):705-711. Published 2020 May 6.
-Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society. March 2015[Minor Revision January 2017]
The work up for this patient with HIVAN and HCV viremia:
He should have similar work up as a non-HIV patients
Specific to HIV, the patient:
Should demonstrate compliance to his cART
The CD4 count should be more than 100 cells/microliter (preferably more than 200 cells/microliter) and should have been stable for at least 3 months
The HIV viral load should have been suppressed for the past six months
Should have no history of opportunistic infection in the past six months
Should have no active infection
Should have no history of PML, chronic intestinal cryptosporiodosis
Should have no active malignancy
Be CDC crossmatch negative
Should be tested for Strongyloidis stercoralis if the patient comes from area endemic for strongyloidosis
Should have ART resistance testing done to ensure that he does not have ART drug resistance
Should be tested for latent TB. If positive, then active TB should be looked for and if diagnosed treated appropriately. If there is latent TB only, it should be treated with one of the acceptable regimens before the transplant
Should be tested for VZV, CMV, EBV, syphillis, Toxoplasma gondii and HTLV 1
Should have been vaccinated against influenza, pneumococcus, MMR, DTP, HiB, meningococcus B, HAV, Hepatitis B and HPV (if at high risk of acquisition)
Needs to be tested for HLA B5701 allele
Needs counseling for drug compliance
The HIV specialist needs to be involved to advise on HAART especially if the patient is on Protease inhibitors or NNRTIs
For the HCV:
The genotype needs to be known and the patient started on appropriate directly acting antiviral agent started to achieve SVR prior to transplant
Need to assess for cirrhosis – if patient has cirrhosis, then it is a relative contraindication to transplantation in an HIV positive patient
Kidney and Pancreas Transplantation In HIV Patients. BTS Guidelines. Second Edition. 2017
The reason for the HLA B5701 testing is to check for abacavir hypersensitivity. There are times we use abacavir and if the patient has HLA B5701 allele, it may predispose him to Steven Johnson Syndrome
Outline the workup required to prepare him for renal transplantation. The workup is as non HIV patients regarding: cardiorespiratory workup, including detailed history of smoking, chest pain, exertional SOB,…etc, family history, unsafe sexual relations, drug abuse or addiction, infectious disease screening: CMV,EBV, HPV, TB-(IGRA+/- PPD), HVC,HBV, HEV, HAV, HSV, Toxoplasma, syphilis , and human T-cell leukemia virus. Workup for diabetes mellitus, body mass index, lipid profile, urinary protein/creatinine ratio, and urinalysis. Serum calcium, phosphorus, potassium, sodium, parathyroid hormone, thyroid hormone, coagulation profile, liver function test (ALT, AST, Alkaline phosphatase, albumin, bilirubin (D+T)) Tumor screening: cervico-anal, hepatic, and full skin exam, …..etc Recommendations state: 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). 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). 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).
Contraindications to 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) Thus before transplant he should be treated for hepatitis C ensuring cure, then can proceed to transplantation with excluding any liver fibrosis, or decompensated cirrhosis. However, HCV coinfection was a significant independent risk factor for graft survival and patient survival. On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection.
All available data have shown that HIV/HCV-coinfection has no impact on HCV-treatment outcome. Management, indication of therapy and follow-up of HCV-infection as per recommendations to non-HIV infected patients. Careful evaluation of potential drug-drug-interactions between HCV drugs and HIV antiretroviral therapy, medication for substance abuse and other co-medications. HIV infection did not adversely affect recipient or allograft survival and was associated with superior outcomes compared with both HCV infection and HIV/HCV coinfection in this population. Thus, pretransplant viral eradication and/or immediate posttransplant eradication should be studied as potential strategies to improve posttransplant outcomes in HCV-infected kidney recipients. Decompensated cirrhosis, chronic kidney disease and patients in HCV can be controlled by new DAA. Psychological/ social evaluation is a must ensuring no more drug abuse by him. Multidisciplinary team work is needed in such cases (infectious, hepatologist, transplant physician, clinical pharmacologist) After transplantation frequent renal monitoring (creatinine, urinalysi , urine protein/creatinine ratio), blood sugar, viral load for HIV and HCV. Better to have a well matched organs with No cross match (FCXM), In order to avoid the use of lymphocyte depleting induction therapy (ATG, Campath). Maintenance therapy would be CNI, MMF, and steroid with frequent blood level monitoring as well as drug-drug interactions documentation and management. References: (1) Xia Y, Friedmann P, Yaffe H, Phair J, Gupta A, Kayler LK. Effect of HCV, HIV and coinfection in kidney transplant recipients: mate kidney analyses. Am J Transplant. 2014 Sep;14(9):2037-47. doi: 10.1111/ajt.12847. Epub 2014 Aug 6. PMID: 25098499. (2) Sawinski D, Locke JE. Kidney Transplantation in a HIV-Positive Recipient. Clin J Am Soc Nephrol. 2019 Apr 5;14(4):614-616. doi: 10.2215/CJN.14051118. Epub 2019 Mar 18. PMID: 30885910; PMCID: PMC6450335. (3) Schlabe S, Rockstroh JK. Advances in the treatment of HIV/HCV coinfection in adults. Expert Opin Pharmacother. 2018 Jan;19(1):49-64. doi: 10.1080/14656566.2017.1419185. PMID: 29252031. (4) Sawinski D, Forde KA, Eddinger K, Troxel AB, Blumberg E, Tebas P, Abt PL, Bloom RD. Superior outcomes in HIV-positive kidney transplant patients compared with HCV-infected or HIV/HCV-coinfected recipients. Kidney Int. 2015 Aug;88(2):341-9. doi: 10.1038/ki.2015.74. Epub 2015 Mar 25. PMID: 25807035; PMCID: PMC5113138. (5) kidney disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl (2011). 2018 Oct;8(3):91-165.
Outline the workup required to prepare him for renal transplantation.
In the indexed case we have HIV positive candidate with ESRD due to HIVAN with HCV coinfection with positive HCV PCR .he is asking for transplantation.
general speaking fitness for kidney transplantation is the same for non-HIV recipients which means the patient should be medically fit and have no evidence of active infection including additional specific eligibility criteria in regards to HIV-positive patients like the patient has expected life survival > 5 years he sustained negative viral load < 50 copies for the last 6 months of the FU and sustained C4D count > 200 cells / microml , no active opportunistic infection including HCV, HBC, HZV, SYPHILIS For last 6 months, No evidence of PML or active malignancy including infection with oncogenic viruses like HPV and risk of anogenital cancers in HIV IVDA with multiple partners anal sex.
active HCV co-infection with positive HCV RNA PCR he should be referred to the hepatology team and assessed for any evidence of chronic liver disease including liver cirrhosis portal hypertension and decompensated liver disease this is an additional contraindication for transplantation and need to assess the degree of liver damage if mild to moderate with compensation liver cirrhosis and mild PHT still we can offer him the DAA therapy that not interact with his current c ART, so need MDT approach including transplant physician, hepatologist and HIV specialist along with virologist to fu and monitor his viremic status for both HCV and HIV in addition HIV/HCV coinfected transplant candidates require a holistic approach with emphasis on the cardiovascular risk profile and low threshold for cardiac catheterization as part of their pretransplant evaluation.
Based on the available evidence and the current guideline recommendation to avoid kidney transplantation with active current infection and such a combination of HIV and HCV co-infection carry high morbidity and poor graft survival poor outcome due to higher rates of post-transplant glomerulonephritis, malignancy, and progression of liver disease., HCV co-infection can result in immunomodulation with increased activation of C4D, CD8, and cytokine expression, so the optimal timing for treating active HCV infection prior to transplantation or immediately after transplantation which should be decided by the transplant team with the recipient after discussing the type of the donors which can be still offered DD with HCV infection which gives him short access to donation and not delays his treatment with curable DAA therapy
also part of the workup is the risk of recurrence of HIV or HCV-related glomerulopathy and h quantitative urine p/c ratio, complement level, mixed cryoglobulin level, and kidney biopsy, and also workup for any other metabolic effects of both viruses like DM, dyslipidemia, and full cardiac risk assessment.
Discuss with the patient the type of donors including the involvement in the HOPE act with HIV positive, HCV positive DD, and get consent to be registered on the waiting list is will shorten his waiting time and will be considered for pre-TX DAA in order to achieve SVR before the transplantation also discuss the availability of ART non-PI ( to avoid drug toxicity and interactions with IS like tacrolimus ) HCV treatment is curative
with the currently available treatment regimens of 8 to 24 weeks. The appropriate duration of therapy is determined by viral genotype, load, the severity of liver disease, and whether the patient has failed prior attempts at therapy and also discuss the risk of rejection which is higher compared to non-HIV candidates, and also the risk of HIV AN recurrence after transplantation although it’s less with the use of c ART but still possible, especially in African American ethnicity with aplo1 gene mutation.
Also need longer chemoprophylaxis therapy for CMV, PJP, fungal infection
References
1. kidney disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl (2011). 2018 Oct;8(3):91-165.
2. Handbook of kidney transplant on 6thedition
3. Farmakiotis D, Weiss Z, Brotherton AL, Morrissey P, Gohh R, Vieira K, Taylor LE, Garland JM. Successful Kidney Transplantation in a Recipient Coinfected with Hepatitis C Genotype 2 and HIV from a Donor Infected with Hepatitis C Genotype 1 in the Direct-Acting Antiviral Era. Case Reports Hepatol. 2020 Jan 29;2020:7679147
I appreciate that you mention genotypes that would shed light on drug resistance. You mention chemoprophylaxis, but not the duration of each of those for CMV, PJP, fungal infection?
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Outline the workup required to prepare him for renal transplantation.
KTX is recommended as the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection (1A). (KDIGO)
I will first evaluate this patient for severity of liver disease & presence of portal hypertension before accepting him for KTX.
If the workup revealed compensated liver cirrhosis (without portal hypertension), I will accept him for isolated KTX & consider for DAA therapy, either before or after TX (1A).(KDIGO HCV GuidelineRecommendation 4.1.3.1)
If there is decompensated cirrhosis, I will refer him for combined liver-kidney transplantation & defer HCV treatment until after transplantation.
Other factors to consider in timing (before versus after) of HCV treatment in relation to KTX include:
Donor type (living vs. deceased)
Waitlist times by donor type
Center-specific policies governing the use of kidneys from
HCV-infected deceased donors
HCV genotype
Severity of liver fibrosis
If the patient in this scenario has a suitable living donor, I will consider for treatment before or after TX according to HCV genotype & anticipated timing of TX.
Regarding HIVAN in this scenario, I will consider the following:
His HIV per se is not a contraindication for KTX; however, he will be wait-listed only if:
He is concordant with treatment (combined ART therapy)
His CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) & have been stable during the previous 3 months.
HIV RNA has been undetectable during the previous 6 months.
No opportunistic infections during the previous 6 months
No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
The most appropriate ART therapy is determined before TX after discussion with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication.
Absolute contraindications to KTX in patients with HIV:
Uncontrolled HIV infection
Habitual and irremediable non-concordance, due for example to major psychiatric disease or persistent substance abuse
MDR HIV infection that cannot be controlled with ART.
Positive CDC crossmatch
Serious ongoing or recurring infection
Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer.
Relative contraindications:
Positive FCXM
Blood-type incompatibility
Treated malignancy, including extracutaneous KS
Severe &/or uncontrolled medical problems that will shorten the patient’s life expectancy.
Those testing positive for latent MBTB are assessed for any evidence of active TB disease.
Those with evidence of active TB disease are treated according to current NICE guidance prior to TX.
Latent MBTB is treated according to current NICE TB guidelines, prior to transplantation.
Transplant candidates from endemic regions are screened for Strongyloides stercoralis infection prior to TX.
ARTs with nephrotoxic potential (tenofovir & atazanavir) are avoided if suitable alternatives are available.
ART with significant drug-drug interactions with CNIs (ritonavir & cobicistat) are avoided if suitable alternatives are available.
References
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Transplant Candidate Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104: S1–S103.
British Transplantation Society Guidelines. Kidney & Pancreas Transplantation in Patients with HIV March 2015 [Minor Revision January 2017]
HIV–HCV coinfection should have an ART regimen selected that will minimise drug–drug interactions with HCV medications and minimise potential liver toxicity (potential drug-drug interaction should be assessed prior to initiation and during treatment period). HIV should be controlled before HCV treatment, particularly in those with advanced HIV immunosuppression (CD4+ count, < 200 cells/mm3). CPG DG suggests that antiretroviral therapy (ART) should be initiated first to allow viral suppression and DAAs should be delayed in patients with HIV/ HCV co-infection. HIV-related opportunistic infections should be treated before initiation of HCV treatment. Treatment of people with a CD4+ cell count greater than 500 cells/mm3 may be deferred until HCV treatment is completed, to avoid drug–drug interactions. DAAs have been established in HIV+/HCV+ recipients as safe and effective, and are expected to improve long-term outcomes. Generally, NRTIs, INSTIs, rilpivirine, and maraviroc do not exhibit relevant interactions with first-line DAAs though tenofovir disoproxil fumarate may be increased with velpatasvir and ledipasvir; tenofovir alafenamide may be preferred. Pharmacoenhancers (ritonavir and cobicistat) and certain NNRTIs (efavirenz, etravirine, and nevirapine) should be avoided due to drug-interactions
Treatment of HCV in HIV/HCV co-infections is as HCV mono-infection with consideration of the complex drug interactions that can occur between DAAs and antiretroviral medications. Currently recommended HCV regimens are equally effective for HCV mono-infection and coinfection with HIV. However, an alternative HCV regimen or an alternative antiretroviral medication regimen may be necessary due to potential drug interactions between the HCV DAAs and certain antiretrovirals
In the general transplant population, treatment of HCV infection has been associated with improved patient and allograft survival. One small study from Miami suggests that the same is true among transplant recipients coinfected with HIV/HCV. In a cohort of 13 patients with HIV/HCV who were transplanted from 2007 to 2017, patient (100% versus 83%) and allograft (100% versus 67%) survival were significantly better in those treated with DAAs and cured of their HCV infection. Post-transplant treatment—although rendered complex by consideration of drug-drug interactions between immunosuppression, ART, and DAAs—is essential
References
1. Kidney & Pancreas Transplantation in Patients with HIV, BTS guidelines, March 2015.
2. Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. doi: 10.1097/QAD.0000000000002518. PMID: 32167973.
3. Sawinski, Deirdre. Kidney Transplantation in Patients with HIV. Kidney360 1(7):p 705-711, July 2020. | DOI: 10.34067/KID.0002112020
4. Werbel WA, Durand CM. Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers. Curr HIV/AIDS Rep. 2019 Jun;16(3):191-203. doi: 10.1007/s11904-019-00440-x. PMID: 31093920; PMCID: PMC6579039.
Outline the workup required to prepare him for renal transplantation.
Patients with cirrhosis of the liver and evidence of active HCV replication are advised against receiving a kidney donation.
HIV-infected people are ineligible for a kidney transplant if they have a serious infection that is chronic or recurrent.
Chronic liver disease is generally incompatible with kidney transplantation.
Patients with HCV and decompensated cirrhosis should be referred for combined liver and kidney transplantation.
In the current scenario patient is hepatitis C positive in addition to HIV infection. Hepatitis C is curable disease. As there is no current donor, and as a rule, the patient will receive a deceased kidney donation, patient should be started on anti-hepatitis C protocol until complete clearance of virus. Patient should be started promptly on 12 weeks protocol.
Patient is currently ineligible for transplantation until he tested negative for Hep C.
Before proceeding with kidney transplantation, patient should be evaluated for liver failure and/or cirrhosis. In case of advanced liver disease, consider combined kidney-liver transplantation.
Thank you Dr Habli
I agree with most of your comments especially contraindication if the patient already developed liver cirrhosis in which case his suitability for liver transplantation should be discussed with liver team.
My comment when there is donor available, can you go ahead with transplant or you wait until HCV viral clearance or not?
Would you like also to list this patient before retroviral medication without dose adjustment trial with tacrolimus?
As per BTS guidlines,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 .
Thank you Dr Gafar.
Can you please expand on what did you mean by treatment may be required in some? What type of treatment you mean and who will require treatment?
Introduction;
-Regarding HCV co-infection, there is controversy about the risk of liver disease progression with immunosuppression and the development of HCV transplant glomerulopathy, with one study demonstrating severe evolution of HCV liver disease in kidney recipients .
-In contrast, a 10-year study that followed 51 HCV-positive kidney transplant recipients with serial liver biopsies showed that HCV infection was not harmful on liver histology in at least 50% of patients, and another study showed stable disease or regression of liver fibrosis in 77% of patients after kidney transplantation.
-Among HIV-positive kidney transplant recipients, somewhat higher early mortality has been observed for those co-infected with HCV (11.7% vs. 3.9% at 1 year).
-So they recommend that kidney transplant candidates are treated for HCV prior to transplantation. In current case (HIVAN with HCV +) not optional for Kidney transplantation, As according BTS guidelines;
-They recommend against kidney transplantation in patients with liver cirrhosis. (1B) and in those with evidence of active HCV replication. (1C)
-Serious ongoing or recurring infection are absolute contraindications to kidney transplantation in patients with HIV. (1D)
-Chronic liver disease is relative contraindications to kidney transplantation. (2D) As according KDIGO guidelines;
-Referring patients with HCV and decompensated cirrhosis for combined liver-kidney transplantation (1B). References;
-Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363: 2004-14.
-Zylberberg H, Nalpas B, Carnot F, et al. Severe evolution of chronic hepatitis C in renal transplantation: a case control study. Nephrol Dial Transplant 2002; 17: 129-33.
-Kamar N, Rostaing L, Selves J, et al. Natural history of hepatitis C virus-related liver fibrosis after renal transplantation. Am J Transplant 2005; 5: 1704-12.
-Roth D, Gaynor JJ, Reddy KR, et al. Effect of kidney transplantation on outcomes among patients with hepatitis C. J Am Soc Nephrol 2011; 22: 1152-60.
Thank you Dr Abou Elenein
I looked at the reference dates with the most recent was 2011. Most of the grave outcome of the combined HCV/HIV infection was prior to DAA . They became available for routine use from 2015. There are many case reports suggesting excellent outcomes for the HCV/HIV co-infection in kidney transplantation (Moreno-Ramirez et al 2020) and (Sawinski et al 2015).
The patient is HIV positive:
To ascertain the suitability of the patient for transplantation:
1] Clinically must have no illnesses consistent with AIDS.
2] No active opportunistic infection under treatment.
3]TB ruled out with Tuberculine skin test.
4] No fungal infection such as PGP, Aspergillosis or strongloydosis.
5] Laboratory: CD4 count of more than 200. HIV RNA copies less than 50 /ml.
6] Kidney biopsy to evaluate histopathologic lesion, in particular collapsing FSGS. Transplantation:
Donor is HIV positive.
induction with ATG and then CNi based maintenance therapy. Intensification of ART alongside with immune-suppressant medications. Modefication of CNi dose when used simultaneously with ART, When the patient is infected with HCV alongside of HIV, risk of adverse outcome is more commonly encountered.
When PCR is positive for HCV in a potential kidney transplant recipient, commencement of anti HCV is recommended prior to transplantation. As a rule of thumb, treatment timing depends on severity of liver disease. Therefore, liver function test and liver scen with /fibro scan is recommended.
Reference:
1] Elmi Muller et al. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501
Kidney transplantation is now accepted as “standard of care” for HIV-positive patients with ESKD.
Kidney transplant candidates with HIV must meet center-specific, general transplant candidate selection criteria in addition to HIV-specific criteria .
There are no established HIV-specific selection criteria for recipients, but most centers follow the patient selection criteria set forth in a National Institutes of Health (NIH) multicenter trial , which specified that patients must have an undetectable viral load and a CD4 count of >200 cells/microL on a stable antiretroviral therapy (ART) regimen for at least six months. These criteria do not exclude patients who have an isolated, low-level, detectable HIV RNA below 200 copies/mL (referred to as a viral blip).
Opportunistic infections are no longer a cause for exclusion, but patients with a history of Kaposi sarcoma, central nervous system (CNS) lymphoma, or progressive multifocal leukoencephalopathy should be considered on a case-by-case basis and may not be considered candidates at many centers.
Patients who are coinfected with hepatitis C virus (HCV) ( as the case here )or hepatitis B virus (HBV) require hepatology evaluation and an assessment of liver fibrosis.
In general, the pretransplant evaluation of individuals with HIV is similar to that of individuals without HIV. This includes screening for latent tuberculosis by tuberculin skin test or interferon-gamma release assay and urine for TB.
In addition, the pretransplant evaluation includes obtaining an HIV viral load, CD4 count, and detailed HIV medication history. Candidates with HIV should be evaluated for potential drug interactions between the patient’s antiretroviral therapy (ART) and planned immunosuppressive agents . Ifpossible, the ART regimen should be switched to a regimen that does not include a protease inhibitor or cobicistat because of their profound effects of the CYP3A4 system. In general, integrase inhibitor-based regimens that include dolutegravir or bictegravir are preferred.
References :
1-BTS 2018
2-uptodate HIV and renal transplantation
This recipient has HIV and HCV co-infection. Thus, his workup needs importance to both of these infections.
Among HIV-positive kidney transplant recipients, somewhat higher early mortality has been observed for those co-infected with HCV (11.7% vs. 3.9% at 1 year, p=0.09) (2). We thus recommend that kidney transplant candidates are treated for HCV prior to transplantation.
The General assessment of this patient would be same as those without these infections.
HIV specific evaluation:
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
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)
HCV specific assessment:
Guidelines are against kidney transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
HCV PCR should be quantified
ultrasound SOS Fibroscan needs to be performed to rule out liver cirrhosis, which would obviate his transplant
LFT
Alpha-feto proteins
Mangement HIV management
The recipient needs treatment for his HIV as according to BTS guidelines he needs following before he is eligible for transplant
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
HCV management:
KDIGO guidelines say that “We recommend that all kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation (1A).”
but, since the recipient is also HIC con-infected it would be better to treat HCV pretransplant if possible
General management:
The recipient needs pretransplant vaccination against HBV, HAV, pneumococcus, VZV, influenza HPV, DPT and MMR whichever are applicable
He also requires post transplant prophylaxis esp against pneumocystis and CMV(depending upon status
Induction preferably by interleukin-2 receptor antagonist (IL-2RA)
Avoid ATG
Maintenance by triple immunosuppression
Monitor for drug interaction between HIV, HCV and immunosuppressive drugs
Post transplant follow up
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
We suggest that patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs
HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria
We suggest that patients who develop new-onset proteinuria (either urine protein-creatinine ratio > 1 g/g or 24-hour urine protein > 1 g on 2 or more occasions) have an allograft biopsy with immunofluorescence and electron microscopy included in the analysis
BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV
Yes agree, actually the reason for evaluating co-infection is to follow the guidelines and exclude those with co-infections because otherwise we wouldn’t those contraindications.
Yes, Prof. The idea is not for immediate transplantation and since we treat HCV, we have to wait as you said for SVR12. How is the situation with HBV/HIV co-infection prof ?
Outline the workup required to prepare him for renal transplantation.
Counseling the recipient:
Most end-stage renal disease (ESRD) patients with viral infections choose kidney transplantation (KTX) over dialysis since KTX has been found to improve long-term survival. However, the studies suggest that the negative impact of HCV in KTX is more evident in HIV+ patients with poor graft outcomes.
The expected recipient should meet transplant center-specific eligibility for organ transplantation:
• CD4+ cell count > 200 cells/μl during the 3 months prior to transplantation for the kidney.
• undetectable plasma HIV viremia .
• Documented adherence with stable antiretroviral treatment regimen
• Absence of ac!ve opportunistic infection and malignancy
• Absence of chronic wasting or severe malnutrition
• Hepatitis C infection if no advanced fibrosis/cirrhosis (for organ types other than liver)
• Access to immunosuppressive agent therapeutic drug monitoring
• Ability to regularly follow up with HIV care providers
HCV-infected HIV-positive kidney transplant patients had increased early mortality. We urge HCV treatment before kidney transplantation.
A sustained virologic response is the goal of hepatitis C virus (HCV) antiviral therapy, which reduces liver-related morbidity and death. HIV/HCV coinfected patients had similar sustained virologic response rates to all oral, direct-acting antiviral (DAA) combo medication. ʼ
With very efficient interferon-free, direct-acting antiviral combination regimens for HCV, most patients, including HIV-positive ones, may get curative all-oral therapy. HIV coinfection accelerates liver disease progression, making HCV antiviral treatment a priority.
In HIV/HCV coinfected patients who are ART-naïve, we start ART four to six weeks before HCV antiviral medication.
HCV antiviral regimen selection for HIV/HCV coinfection is similar to that for monoinfected individuals. Pangenotypic DAA combinations may be delivered without genotype evaluation, facilitating treatment.
Once the patient meets the previous criteria:
Induction with an interleukin-2 receptor antagonist (IL-2RA)
• HIV-positive patients are given triple therapy for maintenance immunosuppression, which is started at the time of kidney transplantation and includes steroids, a calcineurin inhibitor (CNI), and an anti-proliferative agent.
Close monitoring of HCV PCR, HIV RNA, Tac level, renal, and liver function tests post-transplantation
References: Kumar, R. N., & Stosor, V. (2020). Organ transplantation in persons with HIV. AIDS, 34(8), 1107–1116).
Miro, J. M., Grossi, P. A., & Durand, C. M. (2019). Challenges in solid organ transplantation in people living with HIV. Intensive Care Medicine, 45, 398–400
Sawinski D, Forde KA, Locke JE, et al. Race but not Hepatitis C co-infection affects the survival of HIV+ individuals on dialysis in contemporary practice. Kidney Int 2018; 93:706.
The studies suggest that the negative impact of HCV in KTX is more evident in HIV+ patients with poor graft outcomes. but still better than hemodialysis. The patient will start treatment for HIV six weeks before HVC. Then start treatment of HCV. and proceed for transplantation after achieving SVR and fulfill the previous criteria.
Outline the workup required to prepare him for renal transplantation
Introduction
Good counseling will be given to the patient on the nature of the etiology of his CKD and the coinfection with HCV infection.
He will be made to know that according to a study done by UNOS, the prognosis of HIV/HCV coinfection used to be very poor until the advent of DAA which has improved significantly the outcome of the coinfection among those going for kidney transplantation
Generally, the work is the same as other populations and center-specific protocol must be followed.
MDT meetings including hepatitis specialists and clinical psychologists will be done after the initial pre-operative work-up to evaluate all the results and to also counsel the patient and manage expectations.
Pre-operation
Liver function tests with clothing profiles
HCV viral load – must be undetected before surgery it is a living donor
HCV genotype to determine the type of DAA to be used
FBC + differentia
Liver biopsy with ultrasound to evaluate for fibrosis or cirrhosis
DAA will be commenced at least 4-6 weeks after starting HAART and it will be for 12 weeks or until SVR is achieved. Pangenotypic regimen like Sofosbuvir -Velpatasvir has been advised by the expert
HIV viral load must be undetected for 6 months before surgery
CD4 count preferably > 200cells/um
Absence of CNS lymphoma or PML
The patient is regular on HAART medication
Examine for latent TB using IGRA
Investigate for other infectious agents depending on the epidemiology and the location of the recipient
Cardiovascular work-up with ECG, ECHO, and others as the result determine
Intraoperative
Use of IL-2 inhibitor will be encouraged as an induction agent, although ATG can be used depending on the result of the HLA and DSA
Postoperative
Avoidance of PI as part of HAART medication to avoid drug-drug interaction, integrase inhibitor has been encouraged instead
Maintenance immunosuppression will be CNI (tacrolimus preferably), MMF, and prednisolone
HIV viral load after one month, then 3- monthly for the first year
There are two schedules needed to define the best time for the patient’s transplant.
Regarding nephritis secondary to HIV
– HAART schedule
– Control of viral load (< 50 copies) for at least six months
– Avoid nephrotoxic drugs (Tenofovir fumarate and protease inhibitors)
– Adjustment for Creatinine Clearance
– Advise on the importance of keeping the viral load undetectable
– Maintain BMI < 35
– Investigate co-infection with HTLV and other serologies (they must have been done and they only showed us what was altered)
– No history of Lymphoma, LEMP or Cryptosporidium
– Serum CD4 levels greater than 200 cells
– ART resistance profile (Genotyping) if you have a history of positive viral load after starting the HAART regimen
– No opportunistic infections for six months
– Avoid induction with rATG and try to prioritize IL2 inhibitor (Basiliximab)
Regarding the positivity of the hepatitis C virus
– Need to perform treatment for viral suppression
– Drug of choice in our service – Sofosbuvir + Ledispavir for 12 weeks
– There is a need for viral load suppression first before proceeding with transplantation
– Assess liver structure and function
– Upper digestive endoscopy, USG of the abdomen with Doppler and elastase for evaluation of fibrosis
– Avoid induction with rATG and try to prioritize IL2 inhibitor (Basiliximab)
– I would only proceed with the transplant after six months of sustained negative viral load
Patient is both HIV positive and HCV PCR positive .
This patient must counseled there’s increase risk of recurrence and rejection with coinfection ,in addition to more risk of rejection and opportunistic infection.
Patient should be started on both HART and DAA before transplantation.
If feasible and no urgency SVR for at least 6month before schedule.
For transplantation
HIV viral load not detectable and CD 4 more than 200cell per MO for at least 3months.
His liver function and ultrasound. Should be done and consult hepatologist is needed
References:
1-Elmi Muller, kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies. Transplantation.https://journals.lww.com/transplantjournal/toc/2021/07000.
This patient is a ESRD secondary to HIVAN, now HCV positive.
This patient can taken for transplantation if certain measures are taken.
1, treat with HAART therapy,
Until copies less then 50, CD$+T cell >200, no other opportunistic infections.
2, HCV is not a contraindication for transplantation. Plan to treat with DAAs pre-transplant, peri and post-transplantation.
3, Recipient can take HIV and HCV positive donor.
4, post-transplantation with good monitoring for recurrence, liver function test, and other baseline every 3 to 6 monthly.
5, if persistent viremia the suspect drug resistant and need to proceed for testing.
References;
1. Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688.
There is a strong and likely causal association between chronic hepatitis C virus (HCV) infection and glomerular disease
Several types of kidney disease have been recognized including mixed cryoglobulinemia, membranoproliferative glomerulonephritis (MPGN), membranous nephropathy ], and polyarteritis nodosa (PAN). Crescentic glomerulonephritis may be superimposed on any of these glomerular lesions.Less commonly, other glomerular lesions have been reported in HCV-infected patients, including focal segmental glomerulosclerosis (FSGS) [], proliferative glomerulonephritis and fibrillary and immunotactoid glomerulopathies ]. In some patients, glomerular disease may be clinically silent
https://www.uptodate.com/contents/overview-of-kidney-disease-associated-with-hepatitis-c-virus-infection#!
Hepatitis C may share the same route of transmission as HIV; therefore, coinfection is common with nearly 30% of those with HIV also infected with hepatitis C.
Hepatitis C progresses more rapidly in coinfected patients and the higher risk of rejection in HIV+ kidney transplant recipients might require more potent immunosuppression either as prophylaxis against or as treatment of rejection, which may in turn further exacerbate hepatitis C infection and posttransplant liver disease .
Additionally, complex interactions between retroviral medications, induction or maintenance immunosuppression, and HCV-mediated effects on liver metabolism contribute to difficult management of drug levels.
The published experience is scant regarding the potential deleterious impact of HCV coinfection on the outcome of KTX in HIV+ recipients .
It is unknown whether the poorer outcomes seen in the coinfected recipients are due to an additive effect of the separate risks of HIV and HCV or whether there is a potentiating effect of both infections existing together.
Coinfection may additionally exacerbate the effect of HCV on the graft.
Increases in HCV replication due to immunosuppression or the presence of HIV has been hypothesized to increase the risk of allograft glomerular damage.
Additionally, data from existing reports are limited by small sample size, short follow-up and lack of risk-adjusted analyses.
Pretransplant treatment of HCV has been recommended since patients who achieve a sustained virologic response before transplant are unlikely to experience HCV reactivation after KTX, and have a lower risk of developing liver disease and HCV-related glomerulonephritis
prevention or reversal of HIV-related immunosuppression with antiretroviral treatment has been strongly associated with decreased risk of severe liver-related outcomes or death, the adverse impact of HIV coinfection on HCV disease does not appear to be completely ameliorated by the treatment of HIV infection.
So treatment of coinfection in the patient together with full survey about complications of each virus such as liver cirrhosis , malignancy, DM, and other opportunistic infection is mandatory before proceeding to tx with the full investigation and requirement as per guidlines
reference
Y. Xia, P. Friedmann , H. Yaffe.Effect of HCV, HIV and Coinfection in Kidney Transplant Recipients: Mate Kidney Analyses. American Journal of TransplantationVolume 14, Issue 9, September 2014, Pages 2037-2047
his recipient has HIV and HCV co-infection. Thus, his workup needs importance to both of these infections.
Among HIV-positive kidney transplant recipients, somewhat higher early mortality has been observed for those co-infected with HCV (11.7% vs. 3.9% at 1 year, p=0.09) (2). We thus recommend that kidney transplant candidates are treated for HCV prior to transplantation.
The General assessment of this patient would be same as those without these infections.
HIV specific evaluation:
HCV specific assessment:
Mangement
HIV management
HCV management:
General management:
Post transplant follow up
BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV
HIV +ve with co-infection with Hepatitis C
1) General transplant workup
2) Evaluation of the liver and management of the hepatitis C
3) HIV
4) Vaccination pre-transplant
5) Interaction of HAART and immunosuppression – discussion with infectious disease specialist prior to transplant
Co-infected kidney transplant candidates for both HIV and HCV also require an evaluation by hepato-logy and assessment of degree of liver fibrosis, often via transient elasto-graphy or biopsy as indicated. The lengthier and more complex evaluation process can create additional barriers to waiting list for transplant candidates with HIV. Thus, preemptive referral for patients with HIV who have CKD stage 4 is essential. Transplant centers should be sensitive to the complexities of navigating the evaluation process for individuals who are HIV1 and centralized care that involves coordination with subspecialists whenever possible helps overcome barriers for these patients.
1. General assessment for kidney transplantation candidate.
2. Evaluation of presence of cirrhosis and portal hypertension. If positive, combined liver and kidney TX is needed.
3. Start DAA therapy.
4. Other conditions for TX of HIV patients such as viral load below 50 and CD4+ cells above 200, no opportunistic infection, good compliance with drugs and stable condition during the last 6 months are needed.
5. Evaluation for syphilis, HAV, HBV, HSV, CMV, EBV, VZV, HTLV, toxoplasmosis and latent TB should be performed.
6. Screening for malignancies according to age and gender.
7. Complete vaccination according to immunological status.
8. Considering drug interactions, especially among DAA, HAART, CNIs and other immunosuppressant drugs.
9. Rule out HIVAN.
10. Monitoring for HIV and HCV after TX.
Reference:
Sawinski, D. (2020). Kidney Transplantation in Patients with HIV. Kidney360, 1(7). https://doi.org/10.34067/kid.0002112020
The given recipient has both HIV and HCV coinfection…The patient has HIVAN leading to ESRD and CKD..He is planned renal transplantation….
Among HIV positive kidney transplant patients, there are reports of higher early mortality for those with coinfected with HCV….There is a recommendation from the BTS and ATS to treat HCV prior to transplantation…There are excellent reports of successful transplant of HIV/HCV infection after the advent of DAA…
HIV specific work up include – rule out oppurtunistic infection which are active in him, absence of HIV resistance (non responsive to HAART), HIV Viral load not detected or less than 200 copies/ml maybe suitable for transplant (atleast 3 months in a year), CD4 count > 200 cells in 6 months. They should undergo serological testing for syphilis, HSV, EBV, CMV, Toxoplasma, HPV…He should be tested to rule out Latent TBI by IGRA ..
HCV specific assessment – we should make sure that the recipient does not have active HCV infection and those with significant fibrosis F3 and F4 by fibrocan…If there is significant fibrosis kidney transplant alone is contraindicated and there is a need for combined liver kidney transplantation…Baseline LFT, PT INR, AFP, OGD should be done to rule out active infection…the KDIGO recommendation is to treat all HCV recipients of kidney transplant with DAA…This can be done before or even after renal transplantation ..AS the recipient is co infected it is better to treat HCV before renal transplantation…
The general mangement of such a patient would be to get a compatible donor of same blood group with good HLA match and negative DSA to minimize immunosuppression…IL2 receptor antagonist should be used if possible….There is a need to monitor for drug interaction between CART, DAA and immunosuppressive….we should also ensure that the patient are vaccinated against HBV, HAV, pneumococcus, VZV, influenza and COVID…
Routine monitoring of HIV RNA and Cd4 count are done every 3 months after transplant…It is imperative to check the HCV RNA levels also post transplant depending on the time taken to achieve SVR prior to transplantation…. Those with proteinuria after transplant should undergo a renal biopsy to rule out HCV GN …
This patient will need to be evaluated for extra criteria due to HIV and liver status
1- HIV:
– HIV RNA levels<50 copies/mL or undetectable in the last 6 months
– CD4 T-cell counts >200 – stable in last 3months
– Compliance to HAART for last 3months
– No drug resistance
– No opportunistic infection
– No malignity
– Evaluate HAART treatment and use of a protease inhibitor that can be switched.
2 – More careful exclusion of HBV;
– Serology for HBcAg and depending on the result, new tests, with HBV DNA PCR being the most definitive.
3 – Assessment of liver status:
– Exclude decompensated cirrhosis or clinically significant portal hypertension. If existing, associated liver transplantation would have to be evaluated.
Patient is HIV+ (with HIVAN) and HCV+
1. General assessment for any transplant candidate.
2. Evaluation for severity of liver disease – cirrhosis and portal hypertension
– Compensated cirrhosis, and no portal hypertension à isolated kidney transplantation,
– Decompensated cirrhosis or clinically significant portal hypertension à combined liver–kidney transplantation.
He should be given DAA therapy, either before or shortly after transplantation.
3. HIV related inclusion criteria for work up
– HIV RNA levels<50 copies/mL or undetectable in last 6 months
– CD4 T-cell counts >200, stable in last 3months
– Compliance to HAART for last 3months
– No h/o drug resistance
– No opportunistic infection / PML/ cryptosporidium / lymphoma
4. Infection screening:
4.A – Serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii.
4.B – Rule out TB: IGRA / Quantiferon-TB gold test (+/- Montoux) for latent TBI
– If positive for LTBI, assessed for any evidence of active TB disease.
– Treatment of LTBI / active TBI as per NICE Tuberculosis Guidelines.
5. Cancer Screening – 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.
6. Immunization / Vaccination
HBV and Hep AV vaccines if non-immune
Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients.
Varicella zoster vaccine is given to non-immune patients with CD4 cell counts >200 cells/µL.
Influenza vaccine is administered annually to patients awaiting solid organ transplantation
Diphtheria, pertussis, tetanus (DPT) vaccine is administered to all patients
Measles, mumps, and rubella (MMR) vaccine is given if he is nonimmune to measles.
7. A dose-finding trial of CNI prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
Pre-emptive switching from boosted protease-inhibitors (PI)-based antiretroviral regimens, if possible, to minimize drug interactions.
8. Access to medications and ability for regular follow up
9. Counselling for recurrence of HIVAN and graft loss
10. Immunosuppression plan:
– induction with Basiliximab and maintenance with TAC, MMF and steroids
11. Regular follow up and monitoring
– PCP prophylaxis life-long required
– monitoring CD 4 counts, HIV RNA, HCV RNA, CNI drug level, RFT, proteinuria, LFT – 3monthly
– AFP and liver USG every 6months
References:
1. KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
2. British Transplantation Society Guidelines 2017. Kidney & Pancreas Transplantation in Patients with HIV
3. Kumara N R, Stosor V. Organ transplantation in persons with HIV. AIDS 2020, 34:1107–1116
Outline the workup required to prepare him for renal transplantation.
The first step will be detailed counselling regarding the pros and cons. Criteria for transplantation include –
No history of opportunistic infections
No active cirrhosis and active HCV replication
CD 4 count more than 200 copies/Ul in last three months.
Adherence with medications
No active infection
No active malignancy
No history of cryptospordia or lymphoma
HIV RNA not detectable in last 6 months
Access to medications and ability for regular follow up
Standard pre transplant infection screen should be done and immunization protocols followed
As regards immune suppression , induction with Basiliximab and maintenance with TAC, MMF and steroids
Regular follow up and drug level monitoring
PCP prophylaxis will be required
CD 4 counts and HIV RNA should be monitored.
Criteria for transplantation:
1. a CD4+ count above 200 cells/µL of blood.
2. HIV-1 RNA viral load suppressed with treatment.
3. Stable cART regimen for over 6 months.
4. When there is HCV PCR positive is associated with higher all-cause mortality.
5. HCV viral genotyping. DAA therapies for the treatment of chronic HCV infection.
6. Exclude cirrhosis, LFTs, Ultrasound, Liver biopsy.
7. Evidence of current vaccine induced/natural immunity to diphtheria, tetanus and pertussis, measles, mumps and rubella, pneumococcus, hemophilus influenza, meningococcus B, influenza, VZV, hepatitis A and Hepatitis B.
8. Monitor for HIVAN recurrence post transplant.
· First, he needs a general assessment as a non-infected candidate.
· Next, he needs evaluation for the severity of liver disease and the presence of portal hypertension
· If he has compensated cirrhosis, and no portal hypertension he will go for isolated kidney transplantation, and if he has decompensated cirrhosis or clinically significant portal hypertension he will need a simultaneous liver–kidney transplantation.
· He should be given DAA therapy, either before or shortly after transplantation.
· If he has HIV RNA levels<200 copies/mL, he could be considered suitable for solid organ transplantation if otherwise well and fully adherent with their medications.
· He needs serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii.
· He should be tested for latent TB infection with an interferon-gamma test with or without a concurrent Mantoux test according to NICE Tuberculosis Guidelines.
· If he has a positive test for latent TB infection, he should be assessed and managed for any evidence of active TB disease.
· He should 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.
· Hepatitis B virus and Hepatitis A virus vaccines should be given to non-immune patients.
· Pneumococcal polysaccharide vaccine (PPV-23) is administered to all patients.
· Varicella zoster vaccine is given 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 given if he is nonimmune to measles.
· A dose-finding trial of CNI prior to solid organ transplantation in order to determine optimum doses to initiate post-transplant
· Pre-emptive switching from boosted protease-inhibitors (PI)-based antiretroviral regimens, if possible, to minimize drug interactions.
1) KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
2)Kidney & Pancreas Transplantation in Patients with HIV. British Transplantation Society Guidelines
This is a special scenario of coinfection with HIV and HCV
Involvement of hepatologist and ID specialist is early and continuous
In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused.
We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B)
in those with evidence of active HCV replication (1C)
recommendations that kidney and/or pancreas transplant candidates are treated for HCV prior to transplantation.
Pangenomic DAAT is required to treat HCV
HAART (if HAART naïve) – non-PI based regimens are preferred, aim to achieve CD4 >200, undetectable viral load prior to transplantation
As we prepare all recipients we need mdt including nephrologist,hepatologist and infectious
History and clinical examination
CBC KFT LFT PT PTT INR Coagulation profile
Albumin ,virology CMV ,EBV ,HCV,HBV PCR,HIV
Chest abdomen pelvic ct
Assessment for liver fibrosis and portal HTN
treatment with DAA
In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused.
We recommend against kidney and/or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C)
recommendations that kidney and/or pancreas transplant candidates are treated for HCV prior to transplantation.
HIV and HCV coinfection:
HIV positive infection: criteria prior transplantation which are: CD4+ count more than200 cells/µL of blood.
Treatment to suppress HIV-1 RNA viral load.
Stable cART regimen for over 6 months.
DAA for treatment of chronic HCV infection sustained virologic response 12 weeks after treatment.
PCR of HCV if highly infectious for treatment, and exclusion of liver cirrhosis by doing LFTs& Abdominal US.
Induction using Basiliximab .
Maintenance IS by TAC, Steroids, MMF.
References:
Saxena V, Khungar V, Verna EC, et al. Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: results from the HCV-TARGET study. Hepatology. 2017;66(4):1090-1101.
Reau N, Kwo PY, Rhee S, et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology. 2018;68(4):1298-1307
This sort of transplant need very close and special consideration ,like from HIV point of view:
the recepient is having both HIV and HCV.
Regarding HIV;
need to be on HAART therapy and achieved remission with HIV RNA undetectable for the last 6 month ,adding to that he has to be on non PI regiem base medication (not to interfer with IS). need to have CD4 count of more than 200 .
This patient with HIVAN need to be counselled regarding recurrence of the disease in the transpolanted kidney .
This patient condition with HIV need to be in good health with no OI in the last 6 month and no past hx of PML.
This patient should be counselled regarding his active HCV infection which is have a lot of implication on the treansplanted kidney .
He need to be have normal liver with no sign of cirrhosis or sign of decompensated liver disease .
This patient need post RTX FOLLOW UP WITH THE FOLLOWING:
references;
BTS. giuedline
6. A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. His HCV PCR is positive but HBsAg negative.
Issues/ concerns
– 41yo male, CKD on HD, HIVAN
– HCV PCR positive, HBsAg negative
Outline the workup required to prepare him for renal transplantation. (1, 2)
– it is prudent to carefully evaluate kidney transplant candidates in order to detect and treat coexisting illnesses which may negatively impact the transplant outcomes
– the evaluation determines whether the transplant is feasible and guides post-transplant immunosuppressive therapy
– the evaluation process should be as efficient and cost effective as possible
– preemptive transplantation is associated with improved patient and graft survival
– thorough history and physical examination: (3)
– absolute contraindications: active malignancy (excluding NMSC), active infection, active substance use disorder, reversible kidney disease, documented active and ongoing treatment nonadherence, uncontrolled psychiatric illness, shortened life expectancy
– recipient age alone is not a contraindication to transplantation
– relative contraindications: malnutrition, primary oxalosis, systemic amyloidosis, active systemic diseases that may limit the longevity of the graft e.g., uncontrolled ANCA, SLE, MGUS, severe uncontrolled hyperparathyroidism
– evaluate for medical comorbidities e.g.,
– history of prior surgery especially abdominal surgeries
– drug history i.e., drugs metabolised by cytochrome P450 system can interact with the immunosuppressive agents
– immunization history
– physical activity (i.e., frequency, intensity, type of activity) to assess the patient’s functional status
– detailed physical examination including assessment of BMI and central adiposity, oral examination checking for dental decay, auscultation of carotid bruit, assessment of bilateral femoral and pedal pulses and lower extremity integrity, palpation for abdominal masses e.g., polycystic kidneys, assessment of prior abdominal procedures e.g., PD catheter insertion since this may affect placement of the graft kidney, dialysis access location
– psychosocial assessment to identify behavioral, financial and social issues which may influence adherence and outcomes post-transplant
– the patient must understand the potential risks and benefits of transplantation, the need for lifelong immunosuppressive agents, need for adherence to medication and follow-up
– the patient should be able to give informed consent for transplantation
– patients with psychiatric disorders e.g., mood, anxiety, personality disorders need psychiatric assessment in order to improve access to and success following transplantation
– alcohol and substance use disorders must be addressed prior to transplantation
– assess patient’s prior and current adherence to medications, clinics, dialysis sessions
– patient should have a social support system in place throughout the transplant process
– the patient’s financial status should be assessed and any barriers addressed before transplantation
– laboratory and imaging tests:
– holistic management:
– initiate on HAART (if HAART naïve) – non-PI based regimens are preferred, aim to achieve CD4 >200, undetectable viral load prior to transplantation
– initiate pangenotypic DAA therapy as definitive treatment for the HCV infection – aim for SVR
– treat any other detectable opportunistic infections and offer lifelong prophylaxis
– vaccines preferably given prior to the transplant
– induction therapy – basiliximab is preferred
– maintenance therapy – use a triple regimen (CNI, antimetabolite, corticosteroids)
– monitor CD4 and viral load closely in the immediate post-transplant period
References
1. Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske BL, Kher V, et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020 Apr;104(4S1 Suppl 1):S11-S103. PubMed PMID: 32301874. Epub 2020/04/18. eng.
2. Knoll G, Cockfield S, Blydt-Hansen T, Baran D, Kiberd B, Landsberg D, et al. Canadian Society of Transplantation consensus guidelines on eligibility for kidney transplantation. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne. 2005 Nov 8;173(10):1181-4. PubMed PMID: 16275969. Pubmed Central PMCID: PMC1277045. Epub 2005/11/09. eng.
3. Bunnapradist S, Danovitch GM. Evaluation of adult kidney transplant candidates. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2007 Nov;50(5):890-8. PubMed PMID: 17954303. Epub 2007/10/24. eng.
A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. His HCV PCR is positive but HBsAg negative.
Hep C and HIV co infection management in kidney transplantation.
HIV specific evaluation;
HCV specific evaluation;
Management;
HIV;
HCV;
Other Mgt;
REF;
Outline the workup required to prepare him for renal transplantation.
The first step will be detailed counselling regarding the pros and cons. Criteria for transplantation include –
No history of opportunistic infections
No active cirrhosis and active HCV replication
CD 4 count more than 200 copies/Ul in last three months.
Adherence with medications
No active infection
No active malignancy
No history of cryptospordia or lymphoma
HIV RNA not detectable in last 6 months
Access to medications and ability for regular follow up
Standard pre transplant infection screen should be done and immunization protocols followed
As regards immune suppression , induction with Basiliximab and maintenance with TAC, MMF and steroids
Regular follow up and drug level monitoring
PCP prophylaxis will be required
CD 4 counts and HIV RNA should be monitored.
Outline the workup required to prepare him for renal transplantation.
41year old with CKD secondary to HIVAN, HCV PCR positive HBsAg negative.
Kidney transplantation is associated with better survival rates in HIV positive patients than remaining on dialysis. Hence this patient first needs to be counselled on the pros and cons of transplantation.
This patient has HCV co-infection hence it’s crucial to rule out liver cirrhosis and fibrosis prior to transplantation.
This can be done using U/S and AST to platelet index ratio (APRI). Scores >0.8 and suggestive U/S requires referral to liver specialist.
The absence of liver cirrhosis and fibrosis the patient can be initiated on DAA as awaits kidney transplantation. HCV genotyping should be done to determine the DAA.
If the patient has liver cirrhosis then patient should be referred for combined liver pancreas transplantation.
This patient is known HIV positive with HIVAN though not indicated the patient should be on cART. Some classes of cART are associated with metabolic syndrome and diabetes mellitus. Thus this patient should be screened for diabetes mellitus and if diabetic should be considered for simultaneous pancreas-kidney transplantation.
Other Workups should include:
Should have undetectable HIV RNA for 6 months with CD4 counts above 200cells/ul for 3 months.
Should also be adherent on cART.
Should have no prior history of virological failure.
Testing for HLA-B5701 should be done.
Screening for opportunistic infections should include a detailed history and workups.
TB- screening for latent TB should be done with IGRA and patients who are positive should be screened for active TB.
Patient with history of recent exposure to persons with TB should also be screened for active TB.
CMV- serological testing prior to transplantation.
KS-patient should have no prior history of treatment for kaposi sarcoma.
Should also have no prior history of PML, lymphoma and intestinal cryptosporidiasis.
In endemic ares recipient should also be screened for strongyloides stercolaris.
Serological screening for syphillis, EBV, HCV, toxoplasma gondii, HSV, HTLV1 should be done.
Non-immunised recipients should receive HBV,HAV and VZV vaccine.
Annual influenza vaccine should be given while on the waiting list.
Recipient should be suggested to receive DTP vaccine and those who received more than 10 years ago should get a boaster.
Recipient should receive pneumococcal vaccine (PPV23) and repeated every 3-5years.
Recipients with high risk should receive HPV vaccine.
Non-immunised patients should be suggested to receive MMR vaccine.
Recipient should have their ART reviewed and switched to drugs with minimal drug interactions.
Nephrotoxic ART should be avoided.
The induction therapy should be with IL2RA and lymphocyte depleting agents avoided.
Maintenance should be triple immunotherapy with CNI/mycophenolate/steroids.
References
Kidney & Pancreas Transplantation in Patients with HIV Second Edition Compiled by a Working Party of The British Transplantation Society March 2015[Minor Revision January 2017]
British Transplantation Society Guidelines
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
-counseling regarding the pros & cons of transplantation
-detailed hx focusing on drug failure, hx of opportunistic infections , lymphoma or PML & TB.
– should meet the following criteria:
1.HIV RNA has been undetectable or <50 copies for the last 6 months.
2.no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
3.no hx of opportunistic infection
4. assessment for HCV co-infection; should be no liver cirrhosis or HCV active viral replication.
5. CD4+ cell count > 200 cells/µl during 3 months prior to transplantation
6. Documented adherence with stable antiretroviral treatment regimen
7.Absence of active opportunistic infection and malignancy
8.Access to immunosuppressive agent therapeutic drug monitoring
9. Ability to regularly follow up with HIV care providers
When it comes to a kidney transplant, the vaccination protocol must be followed to the letter and at the right time.
-pre-transplant immunization, annual influenza vaccine & HVP vaccine if risky for HPV acquisition
-induction with basiliximab & maintenance with steroid+tacrolimus+MMF
-good attention & monitoring of drug-drug interactions
-lifelong prophylaxis against Pneumocystis pneumonia
– HIV RNA and CD4+ T-cell counts are monitored regularly, 1 month after transplant and subsequent every 2-3 months for the first year then every 3-6 months .
A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. He is HCV positive but HBsAg negative.
Outline the workup required to prepare him for renal transplantation?
Kidney transplantation is recommended as the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection (1A).
I will first evaluate this patient for severity of liver disease & presence of portal hypertension before accepting him for Kidney transplant.
If the workup revealed compensated liver cirrhosis (without portal hypertension), I will accept him for isolated Kidney transplant and consider for DAA therapy, either before or after transplant (1A). (KDIGO HCV Guideline Recommendation 4.1.3.1)
If there is decompensated cirrhosis, I will refer him for combined liver-kidney transplantation & defer HCV treatment until after transplantation.
HIV/HCV confection is associated with increased mortality, there is controversy about the risk of liver disease progression with immunosuppression and the development of HCV transplant glomerulopathy as higher rates of progression to cirrhosis are detected in patients with HCV/HIV
A transplant infectious disease specialist needs to review HIV and ART history, vaccinations, and tuberculosis risk factors, also with HCV confection, hepatologist assessment is needed along with evaluation of degree of liver fibrosis, often via transient elastography or biopsy as needed.
Wait periods for an HCV-infected organ need to be monitored, and transplant hospitals need to frequently evaluate the danger of postponing HCV antiviral treatment.
Transplant candidates who are HIV/HCV coinfected require a comprehensive strategy with a focus on cardiovascular risk profile and a low threshold for cardiac catheterization.
Other factors to consider in timing (before versus after) of HCV treatment in relation to KTX include:
1. Donor type (living vs. deceased)
2. Waitlist times by donor type
3. Center-specific policies governing the use of kidneys from HCV-infected deceased donors
5. HCV genotype needs to be known and the patient started on appropriate directly acting antiviral agent started to achieve SVR prior to transplant
6. Severity of liver fibrosis
7. If the patient in this scenario has a suitable living donor, I will consider for treatment before or after TX according to HCV genotype & anticipated timing of transplant.
8. Need to assess for cirrhosis – if patient has cirrhosis, then it is a relative contraindication to transplantation in an HIV positive patient.
Regarding HIVAN in this scenario, I will consider the following:
His HIV per se is not a contraindication for Kidney transplant; however, he will be wait-listed only if:
He is concordant with treatment (combined ART therapy)
His CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) & have been stable during the previous 3 months.
HIV RNA has been undetectable during the previous 6 months.
No opportunistic infections during the previous 6 months
No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
The most appropriate ART therapy is determined before TX after discussion with an HIV specialist to anticipate potential drug interactions and appropriate dosing of medication.
Absolute contraindications to kidney transplantation in patients with HIV:
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)
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 (1D)
e) Serious ongoing or recurring infection, including documented history of PM.
f) Active malignancy under treatment, metastatic cancer, disseminated or untreated cancer.
g) Pregnancy.
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)
Other workup components include:
Serologic testing for syphilis, HSV, EBV, CMV, HTLV & Toxoplasma gondii
Tests for latent MBTB (IGRA or Mantoux test)
Those testing positive for latent MBTB are assessed for any evidence of active TB disease.
Those with evidence of active TB disease are treated according to current NICE guidance prior to transplant.
Latent MBTB is treated according to current NICE TB guidelines, prior to transplantation.
Transplant candidates from endemic regions are screened for Strongyloidiasis stercoralis infection prior to transplant.
ARTs with nephrotoxic potential (tenofovir & atazanavir) are avoided if suitable alternatives are available.
ART with significant drug-drug interactions with CNIs (ritonavir & cobicistat) are avoided if suitable alternatives are available.
Reference:
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017]
Successful Kidney Transplantation in a Recipient Coinfected with Hepatitis C Genotype 2 and HIV from a Donor Infected with Hepatitis C Genotype 1 in the Direct-Acting Antiviral Era Received 23 September 2019; Accepted 3 January 2020; Published 30 January 2020
Mazumder S A. Treatment Recommendations for HIV-Infected Patients with Co-infections. Medscape 2022
Sawinski D. Kidney Transplantation in Patients with HIV. Kidney360. 2020;1(7):705-711. Published 2020 May 6.
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Transplant Candidate Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104: S1–S103.
Workup for this patient
Evidence of current vaccine induced/natural immunity to diphtheria, tetanus and pertussis, measles, mumps and rubella, pneumococcus, hemophilus influenza, meningococcus B, influenza, VZV, hepatitis A and Hepatitis B, HPV vaccine is offered to patients at risk of HPV acquisition.
Those from endemic regions are screened for Strongyloides stercoralis infection prior to transplantation.
CD4 cell count, HIV RNA level, current and prior antiretroviral therapies and HIV resistance profile.
Serologic testing for syphilis, HSV, EBV, CMV, VZV, human T cell leukemia virus and toxoplasma gondii.
Liver function tests, ultrasound, check for liver cirrhosis and consult with liver specialist.
Crucial to watch for HIVAN recurrence post transplant.
References
Outline the workup required to prepare him for renal transplantation
HIV positive infection is not contraindication for transplantation but there criteria befor transplantation which are: a CD4+ count above 200 cells/µL of blood.
HIV-1 RNA viral load suppressed with treatment.
Demonstrable concordance to a stable cART regimen for over 6 months.
When there is HCV PCR positive HCV seropositivity is associated with higher all-cause mortality.
DAA therapies for the treatment of chronic HCV infection has been introduced, with cure rates defined as sustained virologic response 12 weeks after treatment of greater than 98%.
We need to PCR of HCV if highly infectious for treatment first ,and we need to exclude liver cirrhosis by doing LFT ,Abd US .
The induction by Basiliximab .
The maintenance by TAC,Steroids, MMF .
References
1.. Saxena V, Khungar V, Verna EC, et al. Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: results from the HCV-TARGET study. Hepatology. 2017;66(4):1090-1101.
2. Reau N, Kwo PY, Rhee S, et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology. 2018;68(4):1298-1307
Patient with HIV and HCV positive should counselling regarding reactivation post transplant
In HIV should be met Criteria of CD4T cell count more than 200 micro/ ml and Viral load less than 50 copies/ ml and no evidence of opportunities infection and malignancy for all 3 months at least and should be adherence to highly antiretroviral therapy
For HCV infection should be do HCV PCR, if high should be treated with direct antiviral therapy prior to transplant and do LFT and ultrasound to role out liver cirrhosis
During transplant should start immunosuppressive therapy consist of basiliximab as induction therapy and maintenance therapy is tacrolimus/ steroid/ MMF.
HIV/HCV co-infection in potential kidney transplant recipients can be very challanging case to manage.
Following work up may be considered on priority apart from routine transplant work up
FOR HIV INFECTION
FOR HCV INFECTION
REF:
Outline the workup required to prepare him for renal transplantation.
For HIV infection :
HCV infection :
*Check TB status and manage accordingly ,latent or active TB should be treated before transplantation .
* Vaccination : HBV, HAV, pneumococcus, VZV, influenza HPV, DPT and MMR vaccines where applicable.
* Prophylaxis against opportunistic infections like CMV &PCP.
* Immunosuppressive treatment : induction preferred with IL2 receptors antagonist with avoidance of lymphocyte depleting agents .
* Monitoring drug level and follow for drug interactions.
Reference:
Plan of management is to
1.To look for any absolute and relative contraindication for transplant.
2.Treat Hepatitis C infection before transplant i.e to have sustained viral response.
3.Treat HIV with cART before transplantation for prerequisite criteria i.e having undetectable HIV RNA for last 6 months, CD4 count >100/microL (ideally >200/microL) for more than 3 months, absence of opportunistic infection in last 6 months, and no history of lymphoma, cryptosporidiosis, and progressive multifocal leukoencephalopathy (PML).
Through history and examination: standard work up for recipient
HIV viral load, CD4 count.
Screening for infection
MDT with liver specialist and infectious disease
HCV antibodies, HCV RNA PCR, Liver function tests, ultrasound abdomen, and portal hypertension (upper gastrointestinal endoscopy).
Standard Pre-transplant immunization.
Flow crossmatch -negative
ART medication review should be done, to avoid nephrotoxic drugs, and drugs with potential interactions with immunosuppressives post-transplant.
A dose-finding trial of calcineurin inhibitors (Tacrolimus) can be done if the patient is wait-listed.
Induction: It should be offered with Basiliximab
Maintenance immunosuppression: Tacrolimus, MMF and steroids.
Post-transplant prophylaxis would include pneumocystis (lifelong), cytomegalovirus (minimum 3 months), toxoplasma (lifelong in seropositive recipients with CD4 <200), mycobacterium avium, treatment of latent tuberculosis if positive
Post-transplant monitoring of HCV RNA, HIV RNA, LFT, and CD4 count (at 1 month and then every 2-3 months for 1 year and then 3-6 monthly) in addition to the standard followed in all transplant recipients.
Watch for drug resistance.
Watch for HIVAN recurrence
References
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV
How can you predict drug resistance in such a patient?
Thank you, Prof for the question.
Yes, we can predict resistance in such a patient as acquired HIVDR occurs when mutations develop to drugs in individuals who have received ARV if there is
a) poor adherence
b) treatment interruptions
c) inadequate drug concentrations,
d) use of sub-optimal drug or combination of any.
WHO recommends 3 survey methods to monitor the prevalence of acquired HIV drug resistance:
Both nationally representative methods generate estimates of acquired HIV drug resistance among people with viral non-suppression (≥1000 copies/ml) taking dolutegravir-containing and non-dolutegravir-containing ART. The sentinel method focuses on HIV resistance to dolutegravir among individuals receiving dolutegravir-containing ART with confirmed viral non-suppression.
References
Nachega JB, Marconi VC, van Zyl GU, Gardner EM, Preiser W, Hong SY, Mills EJ, Gross R. HIV treatment adherence, drug resistance, virologic failure: evolving concepts. Infect Disord Drug Targets. 2011 Apr;11(2):167-74. doi: 10.2174/187152611795589663. PMID: 21406048; PMCID: PMC5072419.
WHO: Global HIV Programme
A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) . His HCV PCR is positive but HBsAg negative.
Outline the workup required to prepare him for renal transplantation.
It is accepted for our case to proceed for kidney transplantation but we should explain worse outcome of graft survival with coinfection with HIV and HCV, no special consideration should be taken.
Recipient with HIV should fulfill these criteria:
a) patients who 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 .
Pre-transplant immunization
• Hepatitis B virus (HBV) vaccine is administered to all non-immune patients (HBV surface antibody titers <10 mIU/mL).
• Hepatitis A virus (HAV) vaccine, 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), (MMR) vaccine is administered to all patients (2D)
Immunosuppression:
Induction therapy is with an interleukin-2 receptor antagonist (IL-2RA), preferred than ATG, with triple tacrolimus based therapy and bear in mind the drug-drug interaction .
Post-transplant prophylaxis
• Life-long 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.
• 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 .
HCV work up:
Long-term outcome of HCVR+ transplanted with kidneys from HCVD+ seems good in terms of patient survival, graft survival and liver disease and HCVD+ was not a significant risk factor for mortality, graft failure and liver disease among HCVR+.
Recipient should have compensated cirrhosis, or early fibrosis with absence of portal hypertension, will go ahead to transplant and then treat with DAA after the surgery for 12 weeks according to the genotype with strict follow up.
However, if there is decompensated cirrhosis and portal HTN > 10mmHg with hepatologist assessment, will look for simultaneous liver and kidney transplantation and then treat the recipient with DAA after the surgery.
Close follow-up of patients with careful monitoring for early detection of post-transplant liver complications might have been decisive.
References:
1.British Transplantation Society. Kidney and Pancreas Transplantation in patients with HIV.
2.Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688.
3-(KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS
4- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS).
I make note of close liaison with hepatologist in deciding about kidney or kidney and liver transplant in this situation
The index patient is an ESRD patient on hemodialysis with basic disease of HIVAN (HIV associated nephropathy) with co-infection in form of HCV positivity, while HBsAg is negative.
The patient can be taken up for a kidney transplant if certain conditions are met (1). These include being concordant with cART treatment, having undetectable HIV RNA for last 6 months, CD4 count >100/microL (ideally >200/microL) for more than 3 months, absence of opportunistic infection in last 6 months, and no history of lymphoma, cryptosporidiosis, and progressive multifocal leukoencephalopathy (PML).
Presence of pregnancy, active malignancy, serious ongoing infection, multi-drug resistant HIV infection, a positive CDC crossmatch, substance abuse, major psychiatric illness, and CD4 <100 with persistently detectable HIV RNA in previous 3 months are absolute contraindications for kidney transplant. Relative contraindications include a positive flowcytometry cross match, ABO incompatibility, treated malignancy, uncontrolled medical problems, chronic liver disease, HTLV infection, and BMI >35 (1).
Pre-transplant assessment: It would, in addition to the standard work-up for a transplant recipient, include detailed history (including treatment history), physical examination, HIV viral load, CD4 count, as well as 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 (1).
Pre-transplant immunization with HBV vaccine, Hepatitis A vaccine, pneumococcal vaccine, varicella zoster vaccine, and influenza vaccine is recommended. In addition vaccination with DTP, MMR and HPV vaccine is also suggested (1).
cART medication review should be done, to avoid nephrotoxic drugs, and drugs with potential interactions with immunosuppressives post-transplant.
Recipient evaluation with respect to HCV status: The recipient should be evaluated with respect to positive HCV status – anti-HCV antibodies, HCV RNA PCR, Hepatitis B virus infection assessment (HBsAg is negative in the index patient), hepatology consultation, Liver function tests, ultrasound abdomen, and assessment of liver fibrosis (elastography, liver biopsy) and portal hypertension (upper gastrointestinal endoscopy). In presence of advanced liver fibrosis, a combined liver and kidney transplant would be required (2,3).
Active HCV replication is a contraindication for transplantation according to the BTS guidelines due to increased mortality seen with HCV/HIV co-infection (1). Patient can be considered for renal transplantation only if there is plan to treat HCV infection using DAAs either pre-transplant, or in early post-transplant period (2).
Use of HCV positive organ followed by post-transplant DAA therapy can increase the pool of organs available (4). So, if there is a possibility of receiving a kidney in next 24 weeks, treatment with DAAs can be withheld till transplant, and should be started in early post-transplant period (3).
The recipient can be eligible for both HIV positive donor (with HIV viral load <50 copies/ml and CD4>200 for at least 6 months and no history of virological failure or drug resistance) as well as HCV positive donors, thereby increasing the donor pool for him.
A dose-finding trial of calcineurin inhibitors (Tacrolimus) can be done if the patient is wait-listed for cadaveric donor (1,5).
Induction: It should be offered, with Basiliximab in majority.
Maintenance immunosuppression: Tacrolimus, MMF and steroids.
Post-transplant prophylaxis would include pneumocystis (lifelong), cytomegalovirus (minimum 3 months), toxoplasma (lifelong in seropositive recipients with CD4 <200). Post-transplant monitoring of HCV RNA, LFT, HIV RNA and CD4 count (at 1 month and then every 2-3 months for 1 year and then 3-6 monthly) in addition to the standard followed in all transplant recipients. Drug resistance testing may be required in case of persistent viremia.
References:
You state that the prophylaxis duration for pneumocystis (lifelong) and for toxoplasma (lifelong in seropositive recipients with CD4 <200).
Do you have separate drugs for these 2?
Thank you professor.
Co-trimoxazole can be used as prophylaxis for both pneumocystis as well as toxoplasmosis. The difference lies in the dosage recommended. For pneumocystis, the dose recommended is 480 mg daily, while for toxoplasmosis, the dose is 960 mg daily.
Reference:
Recipient preparation would start by proper counselling with details concerning both advantages and disadvantages (increased susceptibility to opportunistic infections, rejection episodes, recurrence of HIVAN, increased viral replication of HCV and HIV).
Detailed history taking is a must regarding; dialytic complications, blood transfusions, opportunistic infections, history suggestive of PML, history of symptoms suggestive of TB , other comorbid diseases as DM ,HTN ,obesity and smoking.History suggesting malignancies and lymphomas must be excluded.
Vaccination protocol must be fully applied within proper timing in relation to renal transplantation.
Being HCV positive is known to a common co-infection in PWLHIV. Hepatology consultation is crucial to assess HCV load, liver enzymes, and hepatic tissue status after performing fibroscan as well to be able to tailor the best treatment protocol for this patient and exclude the need of simultaneous liver kidney transplantation.
Regarding HIV ,it is mandatory to check proper patient adherence to c ART therapy ,undetectable levels of HIV RNA is a must along with ideal CD4 count ( from 100 to 200 cells /ul is advised not to be less ).
Ensure the availability of insurance to allocate both antiviral medications for HIV and HCV.
Full examination for the patient in multisystem approach as cardiac and chest as well as other body systems to assess fitness for renal transplantation operation.
Routine tests would be besides other expected viral infections as EBV, TB quantiferon tests, HSV, Toxoplasma and other suspected or endemic diseases.
The better the matching, the better results that can be achieved with less doses of immunosuppression.
Immunosuppression is advised to be triple regimen tacrolimus based with the best prophylaxis to be extended for long term especially for CMV and PCP.
Reference
British transplantation society guidelines
https://bts.org.uk/wp-content/uploads/2016/09/05_BTS_Kidney_HIV-1.
https://www.ncbi.nlm.nih.gov/books/NBK559134/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925992/
I like you emphasis on adherence to medications in a transplant patient with HIV. Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Immune deficiency is a risk for liver fibrosis and organ insufficiency in patients co-infected with HCV in case of active viral replication. For that reason, the recommendation is against kidney and or pancreas transplantation in patients with liver cirrhosis (1B) and in those with evidence of active HCV replication (1C).
In our scenario, we need to ensure a negative viral load for both HIV &HCV. The patient should also be on cART, clinically stable, without opportunistic infection history for at least the last six months. For his patient, it is wise to give direct antiviral treatment against HCV before transplantation. We need to make sure about the absence of cirrhosis. From this aspect, in addition to routine work-up done for transplant candidates (CBC, biochemistry, viral serology, Abdominal ultrasound etc.), we need consultation and evaluation by gastroenterologists and infectious diseases experienced. We need to check for portal hypertension by doppler and gastroscopy.
We can see diverse lesions in HIV patients. Some of the pathologic findings may be related to the virus itself, while others can be related to the viral gene expression, drug effects or associated infections.
HIV-related kidney disease can be: Gleomuralar dominant or tubulointerstitial dominant
A- Golemurular dominant:
1-podocytopathy (classic HIVAN, FSGS, MCD in the setting of HIV) or can present with mesangial hypercellularity
2- Immune complex-mediated glomerular disease:
Like HIV-negative patients, we can see IgA, Lupus-like, Lupsp nephritis, MPGD or membranous nephropathy.
B- Tubulointerstitial dominant
It can be an acute or chronic tubular injury.
C: dominant vascular injury: TMA in the setting of HIV o arteriosclerosis can be seen
**** Of note, the classic HIVAN was prevalent in the era that preceded ART therapy.
HIVAN pathology was described as collapsing glomerulopathy with interstitial disease, tubular microcysts, and interstitial lymphoplasmacytic inflammation. Diffuse podocyte foot process effacement is also a classic feature.
Clinically, proteinuria in a nephrotic range can be typically seen. Although a biopsy is the gold standard, screening is For that reason, the evaluation of the risk/screening should be done by evaluation for proteinuria, which is classically in nephrotic range.
** In the south African program, 12 patients out of 51 (10 years follow-up; 150 biopsies for clinical indications) were found to have HIVAN
** Workup should include CD4+ cell count, USG, urinalysis and p/cr ratio.
—————————–
1- Waheed, S., Sakr, A., Chheda, N. D., Lucas, G. M., Estrella, M., Fine, D. M., & Atta, M. G. (2015). Outcomes of renal transplantation in HIV-1 associated nephropathy. PLoS One, 10(6), e0129702.
2- Muller, E., Botha, F. C., Barday, Z. A., Manning, K., Chin-Hong, P., & Stock, P. (2021). Kidney transplantation in HIV positive patients: current practice and management strategies. Transplantation, 105(7), 1492.
What is the risk of recurrence of HIVAN.
Thank you, Prof. Ajay Sharma; I found different numbers, and the studies are mostly retrospective. So I could not find an approximate risk ratio to write exactly (Till moment; I will search again)
I appreciate level of recommendation in relation to each advice in relation to the natural history of HIV infection and co-infection with HCV, and corresponding mode of treatment indicated.
Workup of KT for HIV positive patient co-infected with HCV(1,2,3)
1. History and clinical examination to rule out opportunistic infection, complications like PML, liver cirrhosis and malignancy. History related to compliance with cART and response to treatment.
2. CD4+ cell count ,HIV RNA and HCV RNA to rule out active viral replication.
3. The transplant recipient should meet the following criteria:
a) HIV RNA has been undetectable during the previous 6 months.
b) No opportunistic infections have occurred during the previous 6 months.
c) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
d) Regarding HCV co-infection; there should be no liver cirrhosis nor HCV active viral replication.
4. Screening for viral hepatitis HBV, HDV and HEV.
5. Screening for other infections; CMV, EBV, HSV, VZV, HTLV, TB, Toxoplasma, Strongyloides stercoralis.
6. To rule out liver cirrhosis and HCC. If present, dual liver and kidney transplant to be considered.
7. DAA for HCV before transplantation.
8. cART for HIV to keep the viral load undetectable.
9. Pre-transplant immunization: for HBV, HAV, VZV, DTP, HPV, MMR, influenza and pneumococcal vaccines.
10.Post-transplant prophylaxis:
a) lifelong prophylaxis against Pneumocystis pneumonia following transplantation.
b) lifelong 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.
c) CMV prophylaxis for a minimum of 3 months for seronegative recipients of organs from CMV seropositive donors.
d) TB prophylaxis when TB exposure is suspected.
e) Prophylaxis against Mycobacterium avium complex (MAC) is indicated when the CD4+ count is ≤ 50 cells/μL, and to be stopped when the CD4 count is >100 cells/μL for 6 months.
11.A full and current medication review looking for drug-drug interaction.
12.Induction therapy with IL-2RA(Basiliximab).
13.Maintenance IS; the triple of CNIs, MMF and prednisolone. mTORi have an anti-HIV effect.
14.Acute rejection is treated in HIV-positive kidney transplant in the same way as HIV-negative kidney transplant recipients.
References
1. Kidney & Pancreas Transplantation in Patients with HIV Second Edition Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017]
2. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
3. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
I appreciate that HIV positive recipients are assessed and treated for Mycobacterium tuberculosis latent infection.
Workup for recipient with HIV and HCV coinfection
For HCV
a) Undetectable viral load.
b) Known compliance with ART.
c) No active opportunistic infections.
d) No associated malignancy.
e) Feasibility to follow up.
f) CD4 cell counts >/200 cells/microL, unless in the liver transplant which is >/100 cells/microL.
References
BTS guidelines
Belga S, Doucette KE. Hepatitis C in non-hepatic solid organ transplant candidates and recipients: a new horizon. World J Gastroenterol. 2016;22(4):1650-1663. 2. Kwong AJ, Kim WR, Lake JR, et al. OPTN/SRTR 2019 annual data report: liver. Am J Transplant. 2021;21(suppl 2):208-315. 3. Health Resources & Services Administration. Organ donation statistics. https:// http://www.organdonor.gov/learn/organ-donation-statistics/detailed-description#fig
Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 2014; 384:241–248. 2. Feinstein MJ, Bahiru E, Achenbach C, Longenecker CT, Hsue P, So-Armah K, et al. Patterns of cardiovascular mortality for HIV-infected adults in the United States: 1999 to 2013. Am J Cardiol 2016; 117:214–220. 3. Morse CG, McLaughlin M, Matthews L, Proschan M, T
I appreciate that HIV positive recipients are assessed and treated for Mycobacterium tuberculosis latent infection.
⭐ HIV per se is not contraindication for Transplantation.
⭐ HCV infection is not CI to transplant ion in presence of DAAV.
👌 👌 However, coexistence of HCV and HIV can worsen the graft and patient outcome.
_accepting transplantation can be done only if HIV prerequisites as (negative PCR, cd4 > 200 cells /ml, no active opportunistic infection , adherent to ART).
👉 plus HCV prerequisites as:
_HCV cure by DAAV prior to transplantation and achieving SVR.
_in addition, exclusion of fibrosis /cirrhosis by US, fibroscan and or biopsy is essential before consideration for Tx.
Brevity for the sake of clarity
Workup for this transplantation:
Need to evaluate general assessment then HIV and HCV co-infection status. As HCV is potentially treatable condition, need to treat prior to transplant.
Evaluation for HIV:
Evaluation for HCV:
General management:
HIV management:
HCV management:
References:
– BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV
– BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis,
I make note of your concern when working up a patient with co-infection of HIV and HCV.
6. A 41-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. His HCV PCR is positive but HBsAg negative.
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Outline the workup required to prepare him for renal transplantation.
Absolute contraindications to kidney transplantation in patients with HIV:
Relative contraindications to kidney transplantation:
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Reference
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of
The British Transplantation Society March 2015 [Minor Revision January 2017]
What is your reason for getting HLA B5701 allele, not that I am objecting to it.
Typing whole sentence in bold or typing in capitals amounts to shouting. Use of bullet points is not well done, at places you have used this along with (a) , (b) and (c) .
-HIV/HCV coinfection is associated with increased mortality, there is controversy about the risk of liver disease progression with immunosuppression and the development of HCV transplant glomerulopathy as higher rates of progression to cirrhosis are detected in patients with HCV/HIV
-A transplant infectious disease specialist need to review HIV and ART history, vaccinations, and tuberculosis risk factors, also with HCV coinfection , hepatologist assessment is needed along with evaluation of degree of liver fibrosis, often via transient elastography or biopsy as needed.
-General assessment have to be carried out as well as specific assessment for HIV and HCV infections
-The recipient has to be evaluated regarding the HIV RNA viral load and CD4-infected cell count , adherence and tolerance of ART ,history of ART resistance .
Also serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus and Toxoplasma gondii are needed.
-Gamma interferon test for latent TB
-Assessment of HCV RNA quantitative level and genotype testing along with cirrhosis evaluation.
-screen for HB s Ag if positive HBV DNA level need to be done
-Cases with chronic hepatitis B or C or persistently abnormal liver function testing need to be evaluated by a hepatologist . if there is active hepatitis or cirrhosis then HBV or HCV will be considered as contraindication for renal transplant, otherwise cases with quiescent disease and a benign liver biopsy can proceed to kidney transplantation, meanwhile treatment can be required
-Assessment for the presence of cervical and/or anal neoplasia
-It is recommended to avoid transplantation in cases with active HCV replication ,extracutaneous Kaposi sarcoma, Castleman’s disease, human herpes virus 8 (HHV8)-related primary effusion lymphoma or Epstein-Barr virus (EBV)-related lymphoma
-Treatment of HIV/HCV infection
Drug-induced liver injury (DILI) after ART is more common in HIV/HCV coinfection; eradication of HCV infection lower the risk of anti retrovirus-associated DILI.
LFT monitoring at 1 month then every 3 months after the initiation of ART.
ART is initiated as recommended in -naive patients. ART should be started at least 4-6 weeks before hepatitis C treatment is initiated.
Liver cirrhosis is evaluated according to the Child-Turcotte-Pugh classification system; hepatically metabolized antiretroviral drugs can be modified or avoided in patients with Child-Pugh class B and C
disease.
Treatment of both HCV and HIV can be complicated by drug interactions, drug toxicities, Many of the directly acting anti-HCV drugs have significant interactions with antiretroviral agents; however, ledipasvir with sofosbuvir and daclatasvir plus sofosbuvir have been efficient.
Reference
– Mazumder S A. Treatment Recommendations for HIV-Infected Patients With Co-infections .Medscape 2022
-Sawinski D. Kidney Transplantation in Patients with HIV. Kidney360. 2020;1(7):705-711. Published 2020 May 6.
-Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society. March 2015[Minor Revision January 2017]
I appreciate the need for a close liaison between transplant team and ID team is essential in light of drug interactions.
The work up for this patient with HIVAN and HCV viremia:
He should have similar work up as a non-HIV patients
Specific to HIV, the patient:
For the HCV:
Kidney and Pancreas Transplantation In HIV Patients. BTS Guidelines. Second Edition. 2017
What is your reason for getting HLA B5701 allele, not that I am objecting to it.
The reason for the HLA B5701 testing is to check for abacavir hypersensitivity. There are times we use abacavir and if the patient has HLA B5701 allele, it may predispose him to Steven Johnson Syndrome
Outline the workup required to prepare him for renal transplantation.
The workup is as non HIV patients regarding: cardiorespiratory workup, including detailed history of smoking, chest pain, exertional SOB,…etc, family history, unsafe sexual relations, drug abuse or addiction, infectious disease screening: CMV,EBV, HPV, TB-(IGRA+/- PPD), HVC,HBV, HEV, HAV, HSV, Toxoplasma, syphilis , and human T-cell leukemia virus.
Workup for diabetes mellitus, body mass index, lipid profile, urinary protein/creatinine ratio, and urinalysis.
Serum calcium, phosphorus, potassium, sodium, parathyroid hormone, thyroid hormone, coagulation profile, liver function test (ALT, AST, Alkaline phosphatase, albumin, bilirubin (D+T))
Tumor screening: cervico-anal, hepatic, and full skin exam, …..etc
Recommendations state:
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).
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).
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).
Contraindications to 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)
Thus before transplant he should be treated for hepatitis C ensuring cure, then can proceed to transplantation with excluding any liver fibrosis, or decompensated cirrhosis.
However, HCV coinfection was a significant independent risk factor for graft survival and patient survival. On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection.
All available data have shown that HIV/HCV-coinfection has no impact on HCV-treatment outcome.
Management, indication of therapy and follow-up of HCV-infection as per recommendations to non-HIV infected patients.
Careful evaluation of potential drug-drug-interactions between HCV drugs and HIV antiretroviral therapy, medication for substance abuse and other co-medications.
HIV infection did not adversely affect recipient or allograft survival and was associated with superior outcomes compared with both HCV infection and HIV/HCV coinfection in this population. Thus, pretransplant viral eradication and/or immediate posttransplant eradication should be studied as potential strategies to improve posttransplant outcomes in HCV-infected kidney recipients.
Decompensated cirrhosis, chronic kidney disease and patients in HCV can be controlled by new DAA.
Psychological/ social evaluation is a must ensuring no more drug abuse by him.
Multidisciplinary team work is needed in such cases (infectious, hepatologist, transplant physician, clinical pharmacologist)
After transplantation frequent renal monitoring (creatinine, urinalysi , urine protein/creatinine ratio), blood sugar, viral load for HIV and HCV.
Better to have a well matched organs with No cross match (FCXM), In order to avoid the use of lymphocyte depleting induction therapy (ATG, Campath).
Maintenance therapy would be CNI, MMF, and steroid with frequent blood level monitoring as well as drug-drug interactions documentation and management.
References:
(1) Xia Y, Friedmann P, Yaffe H, Phair J, Gupta A, Kayler LK. Effect of HCV, HIV and coinfection in kidney transplant recipients: mate kidney analyses. Am J Transplant. 2014 Sep;14(9):2037-47. doi: 10.1111/ajt.12847. Epub 2014 Aug 6. PMID: 25098499.
(2) Sawinski D, Locke JE. Kidney Transplantation in a HIV-Positive Recipient. Clin J Am Soc Nephrol. 2019 Apr 5;14(4):614-616. doi: 10.2215/CJN.14051118. Epub 2019 Mar 18. PMID: 30885910; PMCID: PMC6450335.
(3) Schlabe S, Rockstroh JK. Advances in the treatment of HIV/HCV coinfection in adults. Expert Opin Pharmacother. 2018 Jan;19(1):49-64. doi: 10.1080/14656566.2017.1419185. PMID: 29252031.
(4) Sawinski D, Forde KA, Eddinger K, Troxel AB, Blumberg E, Tebas P, Abt PL, Bloom RD. Superior outcomes in HIV-positive kidney transplant patients compared with HCV-infected or HIV/HCV-coinfected recipients. Kidney Int. 2015 Aug;88(2):341-9. doi: 10.1038/ki.2015.74. Epub 2015 Mar 25. PMID: 25807035; PMCID: PMC5113138.
(5) kidney disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl (2011). 2018 Oct;8(3):91-165.
I appreciate your emphasis on multidisciplinary team work (infectious, hepatologist, transplant physician, clinical pharmacologist).
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Outline the workup required to prepare him for renal transplantation.
In the indexed case we have HIV positive candidate with ESRD due to HIVAN with HCV coinfection with positive HCV PCR .he is asking for transplantation.
general speaking fitness for kidney transplantation is the same for non-HIV recipients which means the patient should be medically fit and have no evidence of active infection including additional specific eligibility criteria in regards to HIV-positive patients like the patient has expected life survival > 5 years he sustained negative viral load < 50 copies for the last 6 months of the FU and sustained C4D count > 200 cells / microml , no active opportunistic infection including HCV, HBC, HZV, SYPHILIS For last 6 months, No evidence of PML or active malignancy including infection with oncogenic viruses like HPV and risk of anogenital cancers in HIV IVDA with multiple partners anal sex.
active HCV co-infection with positive HCV RNA PCR he should be referred to the hepatology team and assessed for any evidence of chronic liver disease including liver cirrhosis portal hypertension and decompensated liver disease this is an additional contraindication for transplantation and need to assess the degree of liver damage if mild to moderate with compensation liver cirrhosis and mild PHT still we can offer him the DAA therapy that not interact with his current c ART, so need MDT approach including transplant physician, hepatologist and HIV specialist along with virologist to fu and monitor his viremic status for both HCV and HIV in addition HIV/HCV coinfected transplant candidates require a holistic approach with emphasis on the cardiovascular risk profile and low threshold for cardiac catheterization as part of their pretransplant evaluation.
Based on the available evidence and the current guideline recommendation to avoid kidney transplantation with active current infection and such a combination of HIV and HCV co-infection carry high morbidity and poor graft survival poor outcome due to higher rates of post-transplant glomerulonephritis, malignancy, and progression of liver disease., HCV co-infection can result in immunomodulation with increased activation of C4D, CD8, and cytokine expression, so the optimal timing for treating active HCV infection prior to transplantation or immediately after transplantation which should be decided by the transplant team with the recipient after discussing the type of the donors which can be still offered DD with HCV infection which gives him short access to donation and not delays his treatment with curable DAA therapy
also part of the workup is the risk of recurrence of HIV or HCV-related glomerulopathy and h quantitative urine p/c ratio, complement level, mixed cryoglobulin level, and kidney biopsy, and also workup for any other metabolic effects of both viruses like DM, dyslipidemia, and full cardiac risk assessment.
Discuss with the patient the type of donors including the involvement in the HOPE act with HIV positive, HCV positive DD, and get consent to be registered on the waiting list is will shorten his waiting time and will be considered for pre-TX DAA in order to achieve SVR before the transplantation also discuss the availability of ART non-PI ( to avoid drug toxicity and interactions with IS like tacrolimus ) HCV treatment is curative
with the currently available treatment regimens of 8 to 24 weeks. The appropriate duration of therapy is determined by viral genotype, load, the severity of liver disease, and whether the patient has failed prior attempts at therapy and also discuss the risk of rejection which is higher compared to non-HIV candidates, and also the risk of HIV AN recurrence after transplantation although it’s less with the use of c ART but still possible, especially in African American ethnicity with aplo1 gene mutation.
Also need longer chemoprophylaxis therapy for CMV, PJP, fungal infection
References
1. kidney disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl (2011). 2018 Oct;8(3):91-165.
2. Handbook of kidney transplant on 6thedition
3. Farmakiotis D, Weiss Z, Brotherton AL, Morrissey P, Gohh R, Vieira K, Taylor LE, Garland JM. Successful Kidney Transplantation in a Recipient Coinfected with Hepatitis C Genotype 2 and HIV from a Donor Infected with Hepatitis C Genotype 1 in the Direct-Acting Antiviral Era. Case Reports Hepatol. 2020 Jan 29;2020:7679147
I appreciate that you mention genotypes that would shed light on drug resistance.
You mention chemoprophylaxis, but not the duration of each of those for CMV, PJP, fungal infection?
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Outline the workup required to prepare him for renal transplantation.
Other factors to consider in timing (before versus after) of HCV treatment in relation to KTX include:
Regarding HIVAN in this scenario, I will consider the following:
Absolute contraindications to KTX in patients with HIV:
Relative contraindications:
Other workup components include:
References
I appreciate your decision-making depending upon the degree of insult to liver and stage of liver disease.
HIV–HCV coinfection should have an ART regimen selected that will minimise drug–drug interactions with HCV medications and minimise potential liver toxicity (potential drug-drug interaction should be assessed prior to initiation and during treatment period). HIV should be controlled before HCV treatment, particularly in those with advanced HIV immunosuppression (CD4+ count, < 200 cells/mm3). CPG DG suggests that antiretroviral therapy (ART) should be initiated first to allow viral suppression and DAAs should be delayed in patients with HIV/ HCV co-infection. HIV-related opportunistic infections should be treated before initiation of HCV treatment. Treatment of people with a CD4+ cell count greater than 500 cells/mm3 may be deferred until HCV treatment is completed, to avoid drug–drug interactions. DAAs have been established in HIV+/HCV+ recipients as safe and effective, and are expected to improve long-term outcomes. Generally, NRTIs, INSTIs, rilpivirine, and maraviroc do not exhibit relevant interactions with first-line DAAs though tenofovir disoproxil fumarate may be increased with velpatasvir and ledipasvir; tenofovir alafenamide may be preferred. Pharmacoenhancers (ritonavir and cobicistat) and certain NNRTIs (efavirenz, etravirine, and nevirapine) should be avoided due to drug-interactions
Treatment of HCV in HIV/HCV co-infections is as HCV mono-infection with consideration of the complex drug interactions that can occur between DAAs and antiretroviral medications. Currently recommended HCV regimens are equally effective for HCV mono-infection and coinfection with HIV. However, an alternative HCV regimen or an alternative antiretroviral medication regimen may be necessary due to potential drug interactions between the HCV DAAs and certain antiretrovirals
In the general transplant population, treatment of HCV infection has been associated with improved patient and allograft survival. One small study from Miami suggests that the same is true among transplant recipients coinfected with HIV/HCV. In a cohort of 13 patients with HIV/HCV who were transplanted from 2007 to 2017, patient (100% versus 83%) and allograft (100% versus 67%) survival were significantly better in those treated with DAAs and cured of their HCV infection. Post-transplant treatment—although rendered complex by consideration of drug-drug interactions between immunosuppression, ART, and DAAs—is essential
References
1. Kidney & Pancreas Transplantation in Patients with HIV, BTS guidelines, March 2015.
2. Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. doi: 10.1097/QAD.0000000000002518. PMID: 32167973.
3. Sawinski, Deirdre. Kidney Transplantation in Patients with HIV. Kidney360 1(7):p 705-711, July 2020. | DOI: 10.34067/KID.0002112020
4. Werbel WA, Durand CM. Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers. Curr HIV/AIDS Rep. 2019 Jun;16(3):191-203. doi: 10.1007/s11904-019-00440-x. PMID: 31093920; PMCID: PMC6579039.
Close liaison between transplant team and ID team is essential in light of drug interactions.
Outline the workup required to prepare him for renal transplantation.
Patients with cirrhosis of the liver and evidence of active HCV replication are advised against receiving a kidney donation.
HIV-infected people are ineligible for a kidney transplant if they have a serious infection that is chronic or recurrent.
Chronic liver disease is generally incompatible with kidney transplantation.
Patients with HCV and decompensated cirrhosis should be referred for combined liver and kidney transplantation.
In the current scenario patient is hepatitis C positive in addition to HIV infection. Hepatitis C is curable disease. As there is no current donor, and as a rule, the patient will receive a deceased kidney donation, patient should be started on anti-hepatitis C protocol until complete clearance of virus. Patient should be started promptly on 12 weeks protocol.
Patient is currently ineligible for transplantation until he tested negative for Hep C.
Before proceeding with kidney transplantation, patient should be evaluated for liver failure and/or cirrhosis. In case of advanced liver disease, consider combined kidney-liver transplantation.
Thank you Dr Habli
I agree with most of your comments especially contraindication if the patient already developed liver cirrhosis in which case his suitability for liver transplantation should be discussed with liver team.
My comment when there is donor available, can you go ahead with transplant or you wait until HCV viral clearance or not?
Would you like also to list this patient before retroviral medication without dose adjustment trial with tacrolimus?
As per BTS guidlines,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 .
Thank you Dr Gafar.
Can you please expand on what did you mean by treatment may be required in some? What type of treatment you mean and who will require treatment?
Introduction;
-Regarding HCV co-infection, there is controversy about the risk of liver disease progression with immunosuppression and the development of HCV transplant glomerulopathy, with one study demonstrating severe evolution of HCV liver disease in kidney recipients .
-In contrast, a 10-year study that followed 51 HCV-positive kidney transplant recipients with serial liver biopsies showed that HCV infection was not harmful on liver histology in at least 50% of patients, and another study showed stable disease or regression of liver fibrosis in 77% of patients after kidney transplantation.
-Among HIV-positive kidney transplant recipients, somewhat higher early mortality has been observed for those co-infected with HCV (11.7% vs. 3.9% at 1 year).
-So they recommend that kidney transplant candidates are treated for HCV prior to transplantation.
In current case (HIVAN with HCV +) not optional for Kidney transplantation,
As according BTS guidelines;
-They recommend against kidney transplantation in patients with liver cirrhosis. (1B) and in those with evidence of active HCV replication. (1C)
-Serious ongoing or recurring infection are absolute contraindications to kidney transplantation in patients with HIV. (1D)
-Chronic liver disease is relative contraindications to kidney transplantation. (2D)
As according KDIGO guidelines;
-Referring patients with HCV and decompensated cirrhosis for combined liver-kidney transplantation (1B).
References;
-Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363: 2004-14.
-Zylberberg H, Nalpas B, Carnot F, et al. Severe evolution of chronic hepatitis C in renal transplantation: a case control study. Nephrol Dial Transplant 2002; 17: 129-33.
-Kamar N, Rostaing L, Selves J, et al. Natural history of hepatitis C virus-related liver fibrosis after renal transplantation. Am J Transplant 2005; 5: 1704-12.
-Roth D, Gaynor JJ, Reddy KR, et al. Effect of kidney transplantation on outcomes among patients with hepatitis C. J Am Soc Nephrol 2011; 22: 1152-60.
Thank you Dr Abou Elenein
I looked at the reference dates with the most recent was 2011. Most of the grave outcome of the combined HCV/HIV infection was prior to DAA . They became available for routine use from 2015. There are many case reports suggesting excellent outcomes for the HCV/HIV co-infection in kidney transplantation (Moreno-Ramirez et al 2020) and (Sawinski et al 2015).
Thanks so much, our Prof. Dr. Mohsen
noted,
Thanks for your valuable, precise and updated informations
I will review (ISA)
The patient is HIV positive:
To ascertain the suitability of the patient for transplantation:
1] Clinically must have no illnesses consistent with AIDS.
2] No active opportunistic infection under treatment.
3]TB ruled out with Tuberculine skin test.
4] No fungal infection such as PGP, Aspergillosis or strongloydosis.
5] Laboratory: CD4 count of more than 200. HIV RNA copies less than 50 /ml.
6] Kidney biopsy to evaluate histopathologic lesion, in particular collapsing FSGS.
Transplantation:
Donor is HIV positive.
induction with ATG and then CNi based maintenance therapy. Intensification of ART alongside with immune-suppressant medications. Modefication of CNi dose when used simultaneously with ART,
When the patient is infected with HCV alongside of HIV, risk of adverse outcome is more commonly encountered.
When PCR is positive for HCV in a potential kidney transplant recipient, commencement of anti HCV is recommended prior to transplantation. As a rule of thumb, treatment timing depends on severity of liver disease. Therefore, liver function test and liver scen with /fibro scan is recommended.
Reference:
1] Elmi Muller et al. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501
Thanks, Wael
But the guideline said coinfection with HCV is a contraindication for transplantation. Please comment.
Kidney transplantation is now accepted as “standard of care” for HIV-positive patients with ESKD.
Kidney transplant candidates with HIV must meet center-specific, general transplant candidate selection criteria in addition to HIV-specific criteria .
There are no established HIV-specific selection criteria for recipients, but most centers follow the patient selection criteria set forth in a National Institutes of Health (NIH) multicenter trial , which specified that patients must have an undetectable viral load and a CD4 count of >200 cells/microL on a stable antiretroviral therapy (ART) regimen for at least six months. These criteria do not exclude patients who have an isolated, low-level, detectable HIV RNA below 200 copies/mL (referred to as a viral blip).
Opportunistic infections are no longer a cause for exclusion, but patients with a history of Kaposi sarcoma, central nervous system (CNS) lymphoma, or progressive multifocal leukoencephalopathy should be considered on a case-by-case basis and may not be considered candidates at many centers.
Patients who are coinfected with hepatitis C virus (HCV) ( as the case here )or hepatitis B virus (HBV) require hepatology evaluation and an assessment of liver fibrosis.
In general, the pretransplant evaluation of individuals with HIV is similar to that of individuals without HIV. This includes screening for latent tuberculosis by tuberculin skin test or interferon-gamma release assay and urine for TB.
In addition, the pretransplant evaluation includes obtaining an HIV viral load, CD4 count, and detailed HIV medication history. Candidates with HIV should be evaluated for potential drug interactions between the patient’s antiretroviral therapy (ART) and planned immunosuppressive agents .
If possible, the ART regimen should be switched to a regimen that does not include a protease inhibitor or cobicistat because of their profound effects of the CYP3A4 system. In general, integrase inhibitor-based regimens that include dolutegravir or bictegravir are preferred.
References :
1-BTS 2018
2-uptodate HIV and renal transplantation
Thanks, Mohamed
But the guideline said coinfection with HCV is a contraindication for transplantation. Please comment.
Workup for his transplantation:
This recipient has HIV and HCV co-infection. Thus, his workup needs importance to both of these infections.
Among HIV-positive kidney transplant recipients, somewhat higher early mortality has been observed for those co-infected with HCV (11.7% vs. 3.9% at 1 year, p=0.09) (2). We thus recommend that kidney transplant candidates are treated for HCV prior to transplantation.
The General assessment of this patient would be same as those without these infections.
HIV specific evaluation:
HCV specific assessment:
Mangement
HIV management
HCV management:
General management:
Post transplant follow up
BTS Guidelines – UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
BTS Guidelines – Kidney & Pancreas Transplantation in Patients with HIV
Thanks, Abhijit
HIV evaluation
· HIV viral load
· CD4 count
Co-infection evaluation (HCV)
· HCV antibodies
· HCT NAT
· HCV genotyping
Co-infection evaluation (HBV)
· HBsAb
· HBVcAb
Liver evaluation
· Ultrasound
· Fibroscan
· Alpha-feto protein
· LFTs
· Coagulation profile
TB screening
· Interferon gamma release assay (IGRA)
· Tuberculin skin test (TST)
· ESR
· CXR
· Sampling of any specimen for active TBe.g., sputum for gene Xpert, culture
Serologic testing for
· Syphilis
· HSV
· EBV
· EBV
· CMV
· VZT
· Human T cell leukemia virus
· Toxoplasma gondii
General and cardiac evaluation
· Blood sugar
· FBC
· UECs
· Urinalysis
· Ultrasound KUB
· Doppler ultrasound femoral/iliac vessels
· ECG
· Echocardiography
Urology
· Bladder capacity
· MCU
Transplant specific tests
· Blood grouping
· Tissue typing
· Cross-match tests (CDCXM, FCXM)
· DSA screening
Source:
-BTS guidelines 2018
-Organ transplantation in persons with HIV by Rebecca N. Kumar and Valentina Stosor
Thanks, Ben
But the guideline said coinfection with HCV is a contraindication for transplantation. Please comment.
Welcome prof,
Thank you, Ben
HCV is a treatable disease. I would transplant HIV patients after successful eradication of HCV
Yes, Prof. The idea is not for immediate transplantation and since we treat HCV, we have to wait as you said for SVR12. How is the situation with HBV/HIV co-infection prof ?
Counseling the recipient:
Most end-stage renal disease (ESRD) patients with viral infections choose kidney transplantation (KTX) over dialysis since KTX has been found to improve long-term survival. However, the studies suggest that the negative impact of HCV in KTX is more evident in HIV+ patients with poor graft outcomes.
The expected recipient should meet transplant center-specific eligibility for organ transplantation:
• CD4+ cell count > 200 cells/μl during the 3 months prior to transplantation for the kidney.
• undetectable plasma HIV viremia .
• Documented adherence with stable antiretroviral treatment regimen
• Absence of ac!ve opportunistic infection and malignancy
• Absence of chronic wasting or severe malnutrition
• Hepatitis C infection if no advanced fibrosis/cirrhosis (for organ types other than liver)
• Access to immunosuppressive agent therapeutic drug monitoring
• Ability to regularly follow up with HIV care providers
HCV-infected HIV-positive kidney transplant patients had increased early mortality. We urge HCV treatment before kidney transplantation.
A sustained virologic response is the goal of hepatitis C virus (HCV) antiviral therapy, which reduces liver-related morbidity and death. HIV/HCV coinfected patients had similar sustained virologic response rates to all oral, direct-acting antiviral (DAA) combo medication. ʼ
With very efficient interferon-free, direct-acting antiviral combination regimens for HCV, most patients, including HIV-positive ones, may get curative all-oral therapy. HIV coinfection accelerates liver disease progression, making HCV antiviral treatment a priority.
In HIV/HCV coinfected patients who are ART-naïve, we start ART four to six weeks before HCV antiviral medication.
HCV antiviral regimen selection for HIV/HCV coinfection is similar to that for monoinfected individuals. Pangenotypic DAA combinations may be delivered without genotype evaluation, facilitating treatment.
Once the patient meets the previous criteria:
Induction with an interleukin-2 receptor antagonist (IL-2RA)
• HIV-positive patients are given triple therapy for maintenance immunosuppression, which is started at the time of kidney transplantation and includes steroids, a calcineurin inhibitor (CNI), and an anti-proliferative agent.
Close monitoring of HCV PCR, HIV RNA, Tac level, renal, and liver function tests post-transplantation
References:
Kumar, R. N., & Stosor, V. (2020). Organ transplantation in persons with HIV. AIDS, 34(8), 1107–1116).
Miro, J. M., Grossi, P. A., & Durand, C. M. (2019). Challenges in solid organ transplantation in people living with HIV. Intensive Care Medicine, 45, 398–400
Sawinski D, Forde KA, Locke JE, et al. Race but not Hepatitis C co-infection affects the survival of HIV+ individuals on dialysis in contemporary practice. Kidney Int 2018; 93:706.
Thanks, Weam
But the guideline said coinfection with HCV is a contraindication for transplantation. Please comment.
The studies suggest that the negative impact of HCV in KTX is more evident in HIV+ patients with poor graft outcomes. but still better than hemodialysis.
The patient will start treatment for HIV six weeks before HVC.
Then start treatment of HCV. and proceed for transplantation after achieving SVR and fulfill the previous criteria.
Outline the workup required to prepare him for renal transplantation
Introduction
Good counseling will be given to the patient on the nature of the etiology of his CKD and the coinfection with HCV infection.
He will be made to know that according to a study done by UNOS, the prognosis of HIV/HCV coinfection used to be very poor until the advent of DAA which has improved significantly the outcome of the coinfection among those going for kidney transplantation
Generally, the work is the same as other populations and center-specific protocol must be followed.
MDT meetings including hepatitis specialists and clinical psychologists will be done after the initial pre-operative work-up to evaluate all the results and to also counsel the patient and manage expectations.
Pre-operation
Intraoperative
Postoperative
References
Thanks, Isaac
But the guideline said coinfection with HCV is a contraindication for transplantation. Please comment.
There are two schedules needed to define the best time for the patient’s transplant.
Regarding nephritis secondary to HIV
– HAART schedule
– Control of viral load (< 50 copies) for at least six months
– Avoid nephrotoxic drugs (Tenofovir fumarate and protease inhibitors)
– Adjustment for Creatinine Clearance
– Advise on the importance of keeping the viral load undetectable
– Maintain BMI < 35
– Investigate co-infection with HTLV and other serologies (they must have been done and they only showed us what was altered)
– No history of Lymphoma, LEMP or Cryptosporidium
– Serum CD4 levels greater than 200 cells
– ART resistance profile (Genotyping) if you have a history of positive viral load after starting the HAART regimen
– No opportunistic infections for six months
– Avoid induction with rATG and try to prioritize IL2 inhibitor (Basiliximab)
Regarding the positivity of the hepatitis C virus
– Need to perform treatment for viral suppression
– Drug of choice in our service – Sofosbuvir + Ledispavir for 12 weeks
– There is a need for viral load suppression first before proceeding with transplantation
– Assess liver structure and function
– Upper digestive endoscopy, USG of the abdomen with Doppler and elastase for evaluation of fibrosis
– Avoid induction with rATG and try to prioritize IL2 inhibitor (Basiliximab)
– I would only proceed with the transplant after six months of sustained negative viral load
I would PREFEREABLE proceed with the transplant after six months of sustained negative viral load
Thanks Filipe
Explain more. Which viral load you are talking about HIV or HCV or both?
HIV viral load for six months
Hepatitis C sustained viral load for three months would be preferable.