HIV Solid Organ Transplant Candidate/Recipient
Treatment of end-stage organ disease by transplantation of solid organs. This module will focus on kidney and liver transplantation.
Increasing need for kidney and liver transplantation among HIV+ individuals
- Chronic kidney disease (CKD) is common due to HIV-specific causes (HIV-associated nephropathy, antiretroviral toxicity), hepatitis B and hepatitis C-related glomerulopathies, as well as traditional causes of hypertension, diabetes, and cardiovascular disease.
- End-stage renal disease (ESRD) is increasing in prevalence with about 1.5% of the U.S. dialysis population being HIV+.
- End-stage liver disease (ESLD) is also common due to hepatitis B and hepatitis C co-infection, alcohol-related liver disease, and non-alcoholic fatty liver disease.
- HIV+ individuals with ESRD and ESLD have greater waitlist mortality than their HIV- counterparts and decreased access to transplant.
Outcomes of kidney transplantation
- Excellent overall patient and graft survival based on NIH HIV Multisite HIV Transplant Recipient Study as well as U.S. Scientific Registry of Transplant national registry data.
- Increased incidence of allograft rejection, 2- to 4-fold higher than in HIV- individuals.
- AIDS-related infections are rare.
- Inferior outcomes for HIV/HCV co-infected recipients, although this may change with advent of direct-acting antivirals (DAAs) for hepatitis C.
Outcomes of liver transplantation
The following guidelines are generally recommended for HIV+ solid organ transplant candidates:
- Kidney transplant candidates should have a CD4 count of at least 200 cells/uL.
- Liver transplant candidates should have a CD4 count of at least 100 cells/ul (lower threshold is tolerated since there may be lower overall counts from hypersplenism).
- HIV viral replication should be suppressed on antiretroviral therapy < 50 copies/mL. If antiretroviral therapy cannot be tolerated due to liver dysfunction, candidates can still be considered as long as an effective antiretroviral regimen is anticipated post-transplant.
- A history of progressive multifocal leukoencephalopathy or visceral Kaposi’s sarcoma has historically been considered a contraindication to transplant.
- Optimize antiretroviral therapy to avoid drug-drug interactions with immunosuppression. Avoid potent CYP3A4 inhibitors and inducers - see selected drug comments.
- Screen for HPV-related malignancies which have increased incidence and accelerated progression with post-transplant immunosuppression.
- Induction immunosuppression is recommended as it is associated with lower rates of rejection and increased graft survival.
- Antithymocyte globulin (ATG) induction should be considered for individuals with a high risk of rejection. Although it is associated with significant CD4 depletion immediately post-transplant, counts gradually recover over 1-3 years. Early uncontrolled studies reported an association between ATG and bacterial infections requiring hospitalization but larger, more recent studies have not found an increased incidence of infection in those who received ATG.
- HIV-infected donor organs can now be considered for HIV+ recipients under research protocols as a result of the HIV Organ Policy Equity Act of 2013.
- Check CD4 count one-month post-transplant and every 3 months thereafter to guide opportunistic infection prophylaxis. Expect significant decrease in CD4 count for recipients of lymphodepleting immune induction.
- Check HIV viral load 1-month post-transplant and every 3 months thereafter.
- Standard/institutional CMV prophylaxis according to CMV serostatus.
- Pneumocystis prophylaxis is recommended for at least 1 year and until CD4 > 200 cells/uL. Some experts would use longer durations.
- For patients from an endemic area, Histoplasma and coccidioidomycosis prophylaxis is recommended until CD4 > 150 cells/uL.
- Lifelong secondary prophylaxis for Histoplasma and coccidioidomycosis is recommended based on expert opinion.
- Secondary prophylaxis for prior opportunistic infections is recommended for at least one month after transplant and for one month after treatment of allograft rejection with intensified immunosuppression.
- Continue to screen for HPV-related malignanices which have increased incidence and accelerated progression with post-transplant immunosuppression.
Selected Drug Comments
- Most transplant recipients will be on a maintenance immunosuppression regimen consisting of prednisone, mycophenolate mofetil, and a calcineurin inhibitor (CNI).
- The CNI tacrolimus is preferred over cyclosporine due to lower rates of rejection with tacrolimus.
Avoid protease inhibitor- and cobicistat-containing antiretroviral therapy regimens
- Cytochrome P450 inhibitors will markedly decrease metabolism of tacrolimus requiring infrequent and very low doses of calcineurin inhibitors
- This leads to an overall underexposure of immunosuppressants and may partially explain high rates of graft rejection seen in HIV+ transplant recipients.
Caution with some non-nucleoside reverse transcriptase inhibitors regimens
- Potent cytochrome P450 inducers such as efavirenz and etravirine will increase metabolism of calcineurin inhibitors. Co-administration can be managed but doses of calcineurin inhibitors will need to be adjusted if changing on or off an NNRTI based regimen.
- Rilpivirine and doravirine do not have significant interactions with calcineurin inhibitors.
Preferred: INSTI regimens
- No significant drug interactions
- Dolutegravir and bictegravir will inhibit tubular creatinine excretion but do not have any functional impact on glomerular filtration rate.
CCR5 antagonists, maraviroc (MVC)
- No significant drug interactions
- Theoretically, CCR5 blockade may decrease lymphocyte chemotaxis, inflammation, and organ rejection. This hypothesis is supported by epidemiological studies of HIV- kidney transplant recipients that demonstrated excellent long term allograft survival in recipients who did not express CCR5 as a consequence of a homozygous CCR5 delta 32 deletion, studies of HIV- liver transplant recipients homozygous for the CCR5 delta 32 mutation who had reduced acute rejection rates, and a randomized clinical trial of maraviroc in HIV- bone marrow transplant recipients which showed reduced rates of visceral graft-versus host disease. A randomized clinical trial of MVC in HIV+ kidney transplant recipients is ongoing.
- 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. [PMID:30773688]
- Manzardo C, Londoño MC, Castells L, et al. Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study. Am J Transplant. 2018;18(10):2513-2522. [PMID:29963780]
- Locke JE, Gustafson S, Mehta S, et al. Survival Benefit of Kidney Transplantation in HIV-infected Patients. Ann Surg. 2017;265(3):604-608. [PMID:27768622]
- Locke JE, Mehta S, Sawinski D, et al. Access to Kidney Transplantation among HIV-Infected Waitlist Candidates. Clin J Am Soc Nephrol. 2017;12(3):467-475. [PMID:28232406]
- Boyle SM, Lee DH, Wyatt CM. HIV in the dialysis population: Current issues and future directions. Semin Dial. 2017;30(5):430-437. [PMID:28608994]
- Locke JE, Durand C, Reed RD, et al. Long-term Outcomes After Liver Transplantation Among Human Immunodeficiency Virus-Infected Recipients. Transplantation. 2016;100(1):141-6. [PMID:26177090]
- Roland ME, Barin B, Huprikar S, et al. Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls. AIDS. 2016;30(3):435-44. [PMID:26765937]
- Kucirka LM, Durand CM, Bae S, et al. Induction Immunosuppression and Clinical Outcomes in Kidney Transplant Recipients Infected With Human Immunodeficiency Virus. Am J Transplant. 2016;16(8):2368-76. [PMID:27111897]
- Locke JE, Mehta S, Reed RD, et al. A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients. J Am Soc Nephrol. 2015;26(9):2222-9. [PMID:25791727]
- Health Resources and Services Administration (HRSA), Department of Health and Human Services (HHS). Organ procurement and transplantation: implementation of the HIV Organ Policy Equity Act. Final rule. Fed Regist. 2015;80(89):26464-7. [PMID:25985481]
- Abraham AG, Althoff KN, Jing Y, et al. End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis. 2015;60(6):941-9. [PMID:25409471]
- Smith CJ, Ryom L, Weber R, 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(9939):241-8. [PMID:25042234]
- Locke JE, James NT, Mannon RB, et al. Immunosuppression regimen and the risk of acute rejection in HIV-infected kidney transplant recipients. Transplantation. 2014;97(4):446-50. [PMID:24162248]
- Bickel M, Marben W, Betz C, et al. End-stage renal disease and dialysis in HIV-positive patients: observations from a long-term cohort study with a follow-up of 22 years. HIV Med. 2013;14(3):127-35. [PMID:22994610]
- Terrault NA, Roland ME, Schiano T, et al. Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection. Liver Transpl. 2012;18(6):716-26. [PMID:22328294]
- Reshef R, Luger SM, Hexner EO, et al. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med. 2012;367(2):135-45. [PMID:22784116]
- Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med. 2010;363(21):2004-14. [PMID:21083386]
- Subramanian A, Sulkowski M, Barin B, et al. MELD score is an important predictor of pretransplantation mortality in HIV-infected liver transplant candidates. Gastroenterology. 2010;138(1):159-64. [PMID:19800334]
- Murillas J, Rimola A, Laguno M, et al. The model for end-stage liver disease score is the best prognostic factor in human immunodeficiency virus 1-infected patients with end-stage liver disease: a prospective cohort study. Liver Transpl. 2009;15(9):1133-41. [PMID:19718643]
- Frassetto LA, Browne M, Cheng A, et al. Immunosuppressant pharmacokinetics and dosing modifications in HIV-1 infected liver and kidney transplant recipients. Am J Transplant. 2007;7(12):2816-20. [PMID:17949460]
- Carter JT, Melcher ML, Carlson LL, et al. Thymoglobulin-associated Cd4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients. Am J Transplant. 2006;6(4):753-60. [PMID:16539632]
- Fischereder M, Luckow B, Hocher B, et al. CC chemokine receptor 5 and renal-transplant survival. Lancet. 2001;357(9270):1758-61. [PMID:11403814]
- Heidenhain C, Puhl G, Moench C, et al. Chemokine receptor 5Delta32 mutation reduces the risk of acute rejection in liver transplantation. Ann Transplant. 2009;14(3):36-44. [PMID:19644158]
HIV Solid Organ Transplant Candidate/Recipientis the Johns Hopkins Guides Word of the day!