Solid Organ Transplantation for HIV-Infected Individuals
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Purpose of review
The prevalence of end-stage organ disease is increasing among HIV-infected (HIV+) individuals. Individuals with well-controlled HIV on antiretroviral therapy (ART), without active opportunistic infections or cancer, and with specified minimum CD4 cell counts are appropriate transplant candidates. Infectious disease clinicians can improve access to transplantation for these patients and optimize management pre- and post-transplant.
Clinical trials and registry-based cohort studies demonstrate excellent outcomes for select HIV+ kidney and liver transplant recipients with patient and graft survival similar to HIV-uninfected patients. Elevated allograft rejection rates have been observed in HIV+ individuals; this may be related to a dysregulated immune system, drug interactions, or both. Lymphocyte-depleting immunosuppression has been associated with lower rejection rates without increased infections using national registry data. Hepatitis C virus (HCV) co-infection has been associated with worse outcomes; however, improvements are expected with direct-acting antiviral therapies.
Solid organ transplantation should be considered for HIV+ individuals with end-stage organ disease. Infectious disease clinicians can optimize ART to avoid pharmacoenhancers, which interact with immunosuppression. The timing of HCV treatment (pre- or post-transplant) should be discussed with the transplant team. Finally, organs from HIV+ donors can now be considered for HIV+ transplant candidates, within research protocols.
KeywordsHIV infection Solid organ transplantation End-stage renal disease End-stage liver disease Kidney transplant Liver transplant Immunosuppression
The data reported here have been supplied in part by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the SRTR, the Organ Procurement and Transplantation Network (OPTN), or the US Government.
Compliance with ethical standards
Conflict of interest
Ashton A. Shaffer declares that she has no conflict of interest.
Christine M. Durand has received research grants from Bristol Meyers Squibb, Gilead Sciences, Merck Pharmaceuticals, and Viiv Healthcare and has served as a scientific advisor for Bristol Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals.
Human and animal rights and informed consent
With regard to the authors’ research cited in this paper, all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. In addition, all applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Centers for disease control and prevention. HIV surveillance report. 2016. http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Accessed 1 Dec 2017.
- 3.Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N Engl J Med. 1998;338(13):853–60. https://doi.org/10.1056/NEJM199803263381301.CrossRefPubMedGoogle Scholar
- 5.Losina E, Freedberg KA. Life expectancy in hiv. BMJ. 2011;343(d6015). https://doi.org/10.1136/bmj.d6015
- 8.Saran R, Li Y, Robinson B, Abbott KC, Agodoa LY, Ayanian J, et al. US renal data system 2015 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis. 2016;67(3 Suppl 1):Svii, S1–305.Google Scholar
- 9.Razzak Chaudhary S, Workeneh BT, Montez-Rath ME, Zolopa AR, Klotman PE, Winkelmayer WC. Trends in the outcomes of end-stage renal disease secondary to human immunodeficiency virus-associated nephropathy. Nephrol Dial Transplant. 2015;30(10):1734–40. https://doi.org/10.1093/ndt/gfv207.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Bickel M, Marben W, Betz C, Khaykin P, Stephan C, Gute P, 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. https://doi.org/10.1111/j.1468-1293.2012.01045.x.CrossRefPubMedGoogle Scholar
- 16.Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV medicine association of the infectious diseases society of America. Clin Infect Dis. 2005;40(11):1559–85. https://doi.org/10.1086/430257.CrossRefPubMedGoogle Scholar
- 17.Lucas GM, Ross MJ, Stock PG, Shlipak MG, Wyatt CM, Gupta SK, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV medicine association of the infectious diseases society of America. Clin Infect Dis. 2014;59(9):e96–138. https://doi.org/10.1093/cid/ciu617.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Trullas JC, Cofan F, Barril G, Martinez-Castelao A, Jofre R, Rivera M, et al. Outcome and prognostic factors in HIV-1-infected patients on dialysis in the cart era: a gesida/sen cohort study. J Acquir Immune Defic Syndr. 2011;57(4):276–83. https://doi.org/10.1097/QAI.0b013e318221fbda.CrossRefPubMedGoogle Scholar
- 22.Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, McGowan C, 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. https://doi.org/10.1016/S1473-3099(15)00485-5.CrossRefPubMedGoogle Scholar
- 30.Morse CG, McLaughlin M, Matthews L, Proschan M, Thomas F, Gharib AM, et al. Nonalcoholic steatohepatitis and hepatic fibrosis in HIV-1-monoinfected adults with elevated aminotransferase levels on antiretroviral therapy. Clin Infect Dis. 2015;60(10):1569–78. https://doi.org/10.1093/cid/civ101.PubMedPubMedCentralGoogle Scholar
- 31.Vuille-Lessard E, Lebouche B, Lennox L, Routy JP, Costiniuk CT, Pexos C, et al. Nonalcoholic fatty liver disease diagnosed by transient elastography with controlled attenuation parameter in unselected HIV monoinfected patients. AIDS. 2016;30(17):2635–43. https://doi.org/10.1097/QAD.0000000000001241.CrossRefPubMedGoogle Scholar
- 32.Subramanian A, Sulkowski M, Barin B, Stablein D, Curry M, Nissen N, et al. Meld score is an important predictor of pretransplantation mortality in HIV-infected liver transplant candidates. Gastroenterology. 2010;138(1):159–64. https://doi.org/10.1053/j.gastro.2009.09.053.CrossRefPubMedGoogle Scholar
- 35.Stock PG, Roland ME, Carlson L, Freise CE, Roberts JP, Hirose R, et al. Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study. Transplantation. 2003;76(2):370–5. https://doi.org/10.1097/01.TP.0000075973.73064.A6.CrossRefPubMedGoogle Scholar
- 37.•• Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med. 2010;363(21):2004–14. https://doi.org/10.1056/NEJMoa1001197. This prospective observational study showed that select HIV+ individuals with end-stage renal disease were acceptable kidney transplant candidates, with high 1- and 3-year patient and graft survival. It also highlighted concerns for increased allograft rejection in this population.CrossRefPubMedPubMedCentralGoogle Scholar
- 38.•• Terrault NA, Roland ME, Schiano T, Dove L, Wong MT, Poordad F, et al. Outcomes of liver transplant recipients with hepatitis c and human immunodeficiency virus coinfection. Liver Transpl. 2012;18(6):716–26. https://doi.org/10.1002/lt.23411. This prospective observational study showed that select HIV+ individuals with end-stage liver disease were acceptable liver transplant candidates, with reasonable 1- and 3-year patient and graft survival. It further demonstrated the increased risk of HIV and hepatitis C virus (HCV) co-infection on acute rejection, graft loss, and post-transplant mortality.CrossRefPubMedPubMedCentralGoogle Scholar
- 41.• Locke JE, Mehta S, Reed RD, MacLennan P, Massie A, Nellore A, et al. A national study of outcomes among HIV-infected kidney transplant recipients. J Am Soc Nephrol. 2015;26(9):2222–9. https://doi.org/10.1681/ASN.2014070726. This registry-based study compared post-transplant survival for HIV+ vs. HIV- kidney transplant recipients, finding similar results when restricting to those without hepatitis C virus (HCV) coinfection. HIV+/HCV+ coinfected recipients had worse surival overall, emphasizing the need to treat HCV to improve outcomes in these patients.CrossRefPubMedPubMedCentralGoogle Scholar
- 42.• Locke JE, Durand C, Reed RD, MacLennan PA, Mehta S, Massie A, et al. Long-term outcomes after liver transplantation among human immunodeficiency virus-infected recipients. Transplantation. 2016;100(1):141–6. https://doi.org/10.1097/TP.0000000000000829.This registry-based study describes 5- and 10-year outcomes for HIV+ liver transplant recipients. Coinfection with hepatitis C virus (HCV) was common (65%), and was associated with an increased risk of death and graft loss. This emphasizes the importance of incorporating HCV treatment to improve post-transplant outcomes for HIV+ recipients.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.• Locke JE, Gustafson S, Mehta S, Reed RD, Shelton B, MacLennan PA, et al. Survival benefit of kidney transplantation in HIV-infected patients. Ann Surg. 2017;265(3):604–8. https://doi.org/10.1097/SLA.0000000000001761.This registry-based study showed that kidney transplantation conferred improved survival for HIV+ candidates (80% lower risk of death at 5 years) vs. similar HIV+ candidates who remained on dialysis. By demonstrating survival benefit, this study provides evidence that kidney transplantation should be offered to appropriate HIV+ candidates as a superior option compared to dialysis.CrossRefPubMedPubMedCentralGoogle Scholar
- 44.• Locke JE, Reed RD, Mehta SG, Durand C, Mannon RB, MacLennan P, et al. Center-level experience and kidney transplant outcomes in HIV-infected recipients. Am J Transplant. 2015;15(8):2096–104. https://doi.org/10.1111/ajt.13220.This registry-based study found no association between center-level experience with HIV+ kidney transplant recipients and their post-transplant outcomes. It also showed improvements in outcomes for HIV+ recipients who were transplanted more recently.CrossRefPubMedGoogle Scholar
- 45.• Miro JM, Montejo M, Castells L, Rafecas A, Moreno S, Aguero F, et al. Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study. Am J Transplant. 2012;12(7):1866–76. https://doi.org/10.1111/j.1600-6143.2012.04028.x. This matched analysis of a prospective observational Spanish study compared 5-year post-liver transplant survival for HIV/hepatitis C virus (HCV) co-infected recipients to those with HCV alone. These findings showed poorer survival for coinfected recipients, but identified a subset of coinfected recipients with similar 5-year survival to HCV+ recipients.CrossRefPubMedGoogle Scholar
- 46.Coffin CS, Stock PG, Dove LM, Berg CL, Nissen NN, Curry MP, et al. Virologic and clinical outcomes of hepatitis b virus infection in HIV-HBV coinfected transplant recipients. Am J Transplant. 2010;10(5):1268–75. https://doi.org/10.1111/j.1600-6143.2010.03070.x.CrossRefPubMedPubMedCentralGoogle Scholar
- 47.• Blumberg EA, Rogers CC, Practice ASTIDCo. Human immunodeficiency virus in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):169–78. https://doi.org/10.1111/ajt.12109. This review provides additional commentary on the particular treatment considerations for HIV+ transplant candidates and recipients, including a detailed discussion of antiretroviral treatment regimens, prophylaxis for opportunistic infections, and vaccination strategies for these patients.CrossRefPubMedGoogle Scholar
- 52.Conte AH, Kittleson MM, Dilibero D, Hardy WD, Kobashigawa JA, Esmailian F. Successful orthotopic heart transplantation and immunosuppressive management in 2 human immunodeficiency virus-seropositive patients. Tex Heart Inst J. 2016;43(1):69–74. https://doi.org/10.14503/THIJ-14-4746.CrossRefPubMedPubMedCentralGoogle Scholar
- 61.Dalla Gasperina D, Tozzi M, Astuti N, Balsamo ML, Donati D, Rossi A, et al. Pulmonary tuberculosis in an HIV- and hepatitis C virus-coinfected kidney-pancreas transplant recipient: a case report. Transplant Proc. 2011;43(4):1206–9. https://doi.org/10.1016/j.transproceed.2011.02.050.CrossRefPubMedGoogle Scholar
- 62.Akhtar MZ, Patel N, Devaney A, Sinha S, Shankar S, Vaidya A, et al. Simultaneous pancreas kidney transplantation in the HIV-positive patient. Transplant Proc. 2011;43(10):3903–4. https://doi.org/10.1016/j.transproceed.2011.08.093.CrossRefPubMedGoogle Scholar
- 63.Miro JM, Ricart MJ, Trullas JC, Cofan F, Cervera C, Brunet M, et al. Simultaneous pancreas-kidney transplantation in HIV-infected patients: a case report and literature review. Transplant Proc. 2010;42(9):3887–91. https://doi.org/10.1016/j.transproceed.2010.09.003.CrossRefPubMedGoogle Scholar
- 65.• Kucirka LM, Durand CM, Bae S, Avery RK, Locke JE, Orandi BJ, et al. Induction immunosuppression and clinical outcomes in kidney transplant recipients infected with human immunodeficiency virus. Am J Transplant. 2016;16(8):2368–76. https://doi.org/10.1111/ajt.13840. This study using claims data showed that HIV+ kidney transplant recipients treated with antithymocyte globulin (ATG) induction therapy had lower rates of acute rejection. ATG was not associated with increased risk of post-transplant infections. These findings provide further support for the use of ATG in induction therapy for HIV+ transplant recipients.CrossRefPubMedPubMedCentralGoogle Scholar
- 66.• Locke JE, James NT, Mannon RB, Mehta SG, Pappas PG, Baddley JW, et al. Immunosuppression regimen and the risk of acute rejection in HIV-infected kidney transplant recipients. Transplantation. 2014;97(4):446–50. https://doi.org/10.1097/01.TP.0000436905.54640.8c. This national registry study of 516 HIV+ kidney transplant recipients found no statistically significant increases in graft loss for those receiving antithymocyte globulin (ATG) induction therapy and found a 2.6-fold lower risk of acute rejection, compared to receiving no induction. These findings provide support for the use of ATG in induction therapy for HIV+ transplant recipients.CrossRefPubMedGoogle Scholar
- 67.Brehm MA, Markees TG, Daniels KA, Greiner DL, Rossini AA, Welsh RM. Direct visualization of cross-reactive effector and memory allo-specific cd8 T cells generated in response to viral infections. J Immunol. 2003;170(8):4077–86. https://doi.org/10.4049/jimmunol.170.8.4077.CrossRefPubMedGoogle Scholar
- 69.Filaci G, Contini P, Brenci S, Lanza L, Scudeletti M, Indiveri F, et al. Increased serum concentration of soluble HLA-DR antigens in HIV infection and following transplantation. Tissue Antigens. 1995;46(2):117–23. https://doi.org/10.1111/j.1399-0039.1995.tb02487.x.CrossRefPubMedGoogle Scholar
- 72.Scholten EM, Cremers SC, Schoemaker RC, Rowshani AT, van Kan EJ, den Hartigh J, et al. AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients. Kidney Int. 2005;67(6):2440–7. https://doi.org/10.1111/j.1523-1755.2005.00352.x.CrossRefPubMedGoogle Scholar
- 73.Jain AK, Venkataramanan R, Shapiro R, Scantlebury VP, Potdar S, Bonham CA, et al. Interaction between tacrolimus and antiretroviral agents in human immunodeficiency virus-positive liver and kidney transplantation patients. Transplant Proc. 2002;34(5):1540–1. https://doi.org/10.1016/S0041-1345(02)03011-7.CrossRefPubMedGoogle Scholar
- 74.•Sawinski D, Shelton BA, Mehta S, Reed RD, MacLennan PA, Gustafson S, Segev DL, Locke JE. Impact of protease inhibitor-based anti-retroviral therapy on outcomes for HIV+ kidney transplant recipients. Am J Transplant. 2017;17(12):3114–22. https://doi.org/10.1111/ajt.14419. This registry-based study shows the importance of optimizing anti-retroviral therapy to improve post-transplant outcomes for HIV+ individuals. Use of protease-inhibitors in HIV+ kidney transplant recipients was associated with a 1.8-fold higher risk of graft loss and a 1.9-fold risk of death. Avoiding protease-inhibitor-based regimens for HIV+ transplant recipients should be attempted, when feasible.CrossRefPubMedGoogle Scholar
- 75.van Maarseveen EM, Crommelin HA, Mudrikova T, van den Broek MP, van Zuilen AD. Pretransplantation pharmacokinetic curves of tacrolimus in HIV-infected patients on ritonavir-containing cart: a pilot study. Transplantation. 2013;95(2):397–402. https://doi.org/10.1097/TP.0b013e3182734651.CrossRefPubMedGoogle Scholar
- 78.Sulkowski MS, Eron JJ, Wyles D, Trinh R, Lalezari J, Wang C, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313(12):1223–31. https://doi.org/10.1001/jama.2015.1328.CrossRefPubMedGoogle Scholar
- 79.Younossi ZM, Stepanova M, Sulkowski M, Wyles D, Kottilil S, Hunt S. Patient-reported outcomes in patients co-infected with hepatitis C virus and human immunodeficiency virus treated with sofosbuvir and velpatasvir: the astral-5 study. Liver Int. 2017;37(12):1796–804. https://doi.org/10.1111/liv.13462.CrossRefPubMedGoogle Scholar
- 82.Rockstroh JK, Nelson M, Katlama C, Lalezari J, Mallolas J, Bloch M, et al. Efficacy and safety of grazoprevir (mk-5172) and elbasvir (mk-8742) in patients with hepatitis C virus and HIV co-infection (c-edge co-infection): a non-randomised, open-label trial. Lancet HIV. 2015;2(8):e319–27. https://doi.org/10.1016/S2352-3018(15)00114-9.CrossRefPubMedGoogle Scholar
- 83.Brown RS Jr, O’Leary JG, Reddy KR, Kuo A, Morelli GJ, Burton JR Jr, et al. Interferon-free therapy for genotype 1 hepatitis C in liver transplant recipients: real-world experience from the hepatitis C therapeutic registry and research network. Liver Transpl. 2016;22(1):24–33. https://doi.org/10.1002/lt.24366.CrossRefPubMedPubMedCentralGoogle Scholar
- 85.Saxena V, Khungar V, Verna EC, Levitsky J, Brown RS Jr, Hassan MA, 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):1090–101. https://doi.org/10.1002/hep.29258.CrossRefPubMedGoogle Scholar
- 86.Colombo M, Aghemo A, Liu H, Zhang J, Dvory-Sobol H, Hyland R, et al. Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection: a randomized trial. Ann Intern Med. 2017;166(2):109–17. https://doi.org/10.7326/M16-1205.CrossRefPubMedGoogle Scholar
- 91.••Muller E, Barday Z, Mendelson M, Kahn D. HIV-positive-to-HIV-positive kidney transplantation—results at 3 to 5 years. N Engl J Med. 2015;372(7):613–20. https://doi.org/10.1056/NEJMoa1408896. This study of 27 HIV+ kidney transplant recipients of HIV+ donors reports excellent patient and graft survival at 3- (84%) and 5-years (74%) post-transplant and demonstrates the potential for using HIV+ donor organs for HIV+ transplant recipients. US studies investigating HIV+ to HIV+ transplantation are ongoing.CrossRefPubMedPubMedCentralGoogle Scholar
- 92.Health R, Services Administration DoH, Human S. Organ procurement and transplantation: implementation of the HIV organ policy equity act. Final rule. Fed Regist. 2015;80(89):26464–7.Google Scholar