Solid organ transplantation in HIV-infected individuals
- Pablo Tebas, MD
Pablo Tebas, MD
- Professor of Medicine
- University of Pennsylvania
- Section Editors
- Daniel C Brennan, MD, FACP
Daniel C Brennan, MD, FACP
- Editor-in-Chief — Nephrology
- Section Editor — Renal Transplantation
- Professor of Medicine
- Washington University School of Medicine
- John G Bartlett, MD
John G Bartlett, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — HIV; Pulmonary Infections
- Professor Emeritus
- Johns Hopkins University School of Medicine
Liver, kidney, and heart transplantation are the current treatments of choice for advanced organ failure. However, human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for transplantation . One of the principal concerns was that immunosuppression would accelerate HIV/acquired immune deficiency syndrome (AIDS), resulting in increased mortality and a "waste" of organs. (See "Evaluation of the potential renal transplant recipient".)
Since highly active antiretroviral therapy (HAART) became widely available in 1996 , the prognosis of HIV infection has dramatically improved. There have been significant decreases in morbidity and mortality, and, for many individuals with well-controlled viral replication, HIV/AIDS is now a chronic, manageable disease [3,4]. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient".)
Previously, HIV-infected individuals with very advanced disease frequently died from opportunistic infections (OIs). Among such individuals, the presence of chronic diseases, such as renal insufficiency, coronary artery disease, diabetes mellitus, or liver failure (associated with hepatitis B [HBV] or C virus [HCV] coinfection), were not significant causes of mortality. The situation is currently quite different as these comorbidities, as well as others, are real medical problems for many individuals with well-controlled HIV replication [5-8].
Such improvements in the long-term prognosis of those with HIV infection have prompted many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection. A review of the issues surrounding solid organ transplantation in HIV-infected patients is presented here.
OUTCOMES BEFORE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
Prior to the availability of a reliable diagnostic test for HIV infection, some individuals unknowingly infected with HIV underwent solid organ transplantation [9-13]. Others acquired HIV infection by receiving an organ from a HIV-positive individual [14-20].
- Spital A. Should all human immunodeficiency virus-infected patients with end-stage renal disease be excluded from transplantation? The views of U.S. transplant centers. Transplantation 1998; 65:1187.
- Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 1997; 337:734.
- Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338:853.
- Günthard HF, Aberg JA, Eron JJ, et al. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA 2014; 312:410.
- Kaplan JE, Hanson DL, Jones JL, et al. Viral load as an independent risk factor for opportunistic infections in HIV-infected adults and adolescents. AIDS 2001; 15:1831.
- Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis 2000; 30 Suppl 1:S5.
- Bica I, McGovern B, Dhar R, et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001; 32:492.
- Wolfe M, Selik R, Swerdlow DL. Deaths from Non-AIDS-Related Diseases Have Increased as a Proportion of Deaths of HIV-Infected Persons since the Advent of HAART. 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Washington. Abstract 14.
- Tzakis AG, Cooper MH, Dummer JS, et al. Transplantation in HIV+ patients. Transplantation 1990; 49:354.
- Dummer JS, Erb S, Breinig MK, et al. Infection with human immunodeficiency virus in the Pittsburgh transplant population. A study of 583 donors and 1043 recipients, 1981-1986. Transplantation 1989; 47:134.
- Rubin RH, Jenkins RL, Shaw BW Jr, et al. The acquired immunodeficiency syndrome and transplantation. Transplantation 1987; 44:1.
- Shaffer D, Pearl RH, Jenkins RL, et al. HTLV-III/LAV infection in kidney and liver transplantation. Transplant Proc 1987; 19:2176.
- Izzedine H, Launay-Vacher V, Baumelou A, Deray G. Antiretroviral and immunosuppressive drug-drug interactions: an update. Kidney Int 2004; 66:532.
- Ho M. Infection and organ transplantation. In: Anesthesia and organ transplantation, Gelman S (Ed), Saunders, Philadelphia 1987. p.49.
- al-Sulaiman M, al-Khader AA, al-Hasani MK, Dhar JM. Impact of HIV infection on dialysis and renal transplantation. Transplant Proc 1989; 21:1970.
- Keay S, Behrens MT, Klassen D, et al. Impact asymptomatic HIV-1 infection on renal allograft recipients. Transplant Proc 1993; 25:1478.
- Lang P, Niaudet P. Update and outcome of renal transplant patients with human immunodeficiency virus. The Groupe Cooperatif de Transplantation de I'lle de France. Transplant Proc 1991; 23:1352.
- Glassock RJ, Cohen AH, Danovitch G, Parsa KP. Human immunodeficiency virus (HIV) infection and the kidney. Ann Intern Med 1990; 112:35.
- Prompt CA, Reis MM, Grillo FM, et al. Transmission of AIDS virus at renal transplantation. Lancet 1985; 2:672.
- Schvarcz R, Rudbeck G, Söderdahl G, Ståhle L. Interaction between nelfinavir and tacrolimus after orthoptic liver transplantation in a patient coinfected with HIV and hepatitis C virus (HCV). Transplantation 2000; 69:2194.
- Jacobson SK, Calne RY, Wreghitt TG. Outcome of HIV infection in transplant patient on cyclosporin. Lancet 1991; 337:794.
- Vanhems P, Bresson-Hadni S, Vuitton DA, et al. Long-term survival without immunosuppression in HIV-positive liver-graft recipient. Lancet 1991; 337:126.
- Schwarz A, Offermann G, Keller F, et al. The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation--data on four cases and review of the literature. Transplantation 1993; 55:95.
- Purgus R, Tamalet C, Poignard P, et al. Long-term nonprogressive human immunodeficiency virus-1 infection in a kidney allograft recipient. Transplantation 1998; 66:1384.
- Bouscarat F, Samuel D, Simon F, et al. An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1. Clin Infect Dis 1994; 19:854.
- Erice A, Rhame FS, Heussner RC, et al. Human immunodeficiency virus infection in patients with solid-organ transplants: report of five cases and review. Rev Infect Dis 1991; 13:537.
- Gordon FH, Mistry PK, Sabin CA, Lee CA. Outcome of orthotopic liver transplantation in patients with haemophilia. Gut 1998; 42:744.
- Poli F, Scalamogna M, Pizzi C, et al. HIV infection in cadaveric renal allograft recipients in the North Italy Transplant Program. Transplantation 1989; 47:724.
- Bontempo FA, Lewis JH, Gorenc TJ, et al. Liver transplantation in hemophilia A. Blood 1987; 69:1721.
- Ragni MV, Bontempo FA, Lewis JH. Organ transplantation in HIV-positive patients with hemophilia. N Engl J Med 1990; 322:1886.
- Starzl TE, Fung J, Tzakis A, et al. Baboon-to-human liver transplantation. Lancet 1993; 341:65.
- Halpern SD, Ubel PA, Caplan AL. Solid-organ transplantation in HIV-infected patients. N Engl J Med 2002; 347:284.
- Roland MS, Carlson L. Liver and kidney transplantation in HIV-infected patients: A preliminary multi-site experience. 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Washington. Abstract 655.
- Stock P, Roland M, Carlson L, et al. Solid organ transplantation in HIV-positive patients. Transplant Proc 2001; 33:3646.
- Stock PG, Roland ME, Carlson L, et al. Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study. Transplantation 2003; 76:370.
- Abbott KC, Swanson SJ, Agodoa LY, Kimmel PL. Human immunodeficiency virus infection and kidney transplantation in the era of highly active antiretroviral therapy and modern immunosuppression. J Am Soc Nephrol 2004; 15:1633.
- El Sayegh S, Keller MJ, Huprikar S, Murphy B. Solid organ transplantation in HIV-infected recipients. Pediatr Transplant 2004; 8:214.
- Kumar MS, Sierka DR, Damask AM, et al. Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients. Kidney Int 2005; 67:1622.
- Qiu J, Terasaki PI, Waki K, et al. HIV-positive renal recipients can achieve survival rates similar to those of HIV-negative patients. Transplantation 2006; 81:1658.
- Roland ME, Barin B, Carlson L, et al. HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes. Am J Transplant 2008; 8:355.
- Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363:2004.
- Gómez V, Fernández A, Galeano C, et al. Renal transplantation in HIV-infected patients: experience at a tertiary hospital in Spain and review of the literature. Transplant Proc 2013; 45:1255.
- Locke JE, Mehta S, Reed RD, et al. A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients. J Am Soc Nephrol 2015; 26:2222.
- 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; 6:753.
- Canaud G, Dejucq-Rainsford N, Avettand-Fenoël V, et al. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol 2014; 25:407.
- Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med 2010; 362:2336.
- 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; 372:613.
- Calabrese F, Angelini A, Cecchetto A, et al. HIV infection in the first heart transplantation in Italy: fatal outcome. Case report. APMIS 1998; 106:470.
- Calabrese LH, Albrecht M, Young J, et al. Successful cardiac transplantation in an HIV-1-infected patient with advanced disease. N Engl J Med 2003; 348:2323.
- Roland ME, Havlir DV. Responding to organ failure in HIV-infected patients. N Engl J Med 2003; 348:2279.
- Uriel N, Jorde UP, Cotarlan V, et al. Heart transplantation in human immunodeficiency virus-positive patients. J Heart Lung Transplant 2009; 28:667.
- Chin-Hong P, Beatty G, Stock P. Perspectives on liver and kidney transplantation in the human immunodeficiency virus-infected patient. Infect Dis Clin North Am 2013; 27:459.
- Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity 2000; 12:121.
- Doranz BJ, Rucker J, Yi Y, et al. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1996; 85:1149.
- Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 1996; 273:1856.
- Hall IP, Wheatley A, Christie G, et al. Association of CCR5 delta32 with reduced risk of asthma. Lancet 1999; 354:1264.
- Zapico I, Coto E, Rodríguez A, et al. CCR5 (chemokine receptor-5) DNA-polymorphism influences the severity of rheumatoid arthritis. Genes Immun 2000; 1:288.
- Sellebjerg F, Madsen HO, Jensen CV, et al. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis. J Neuroimmunol 2000; 102:98.
- Fischereder M, Luckow B, Hocher B, et al. CC chemokine receptor 5 and renal-transplant survival. Lancet 2001; 357:1758.
- Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 2008; 359:1429.
- Fätkenheuer G, Nelson M, Lazzarin A, et al. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med 2008; 359:1442.
- Reshef R, Luger SM, Hexner EO, et al. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med 2012; 367:135.
- Roland MS, Carlson L, et al. Solid organ transplantation in HIV disease. 8th Conference on Retroviruses and Opportunistic Infections; February 2001; Chicago. Abstract 579.
- Gow PJ, Pillay D, Mutimer D. Solid organ transplantation in patients with HIV infection. Transplantation 2001; 72:177.
- Frassetto L, Baluom M, Jacobsen W, et al. Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency virus-infected liver and kidney transplant recipients. Transplantation 2005; 80:13.
- Sheikh AM, Wolf DC, Lebovics E, et al. Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels. Transplantation 1999; 68:307.
- Fung J. Clinical experiences with HIV and transplantation. Oral Presentation. American Society of Transplantation (AST) Winter Symposium; January 19, 2002; Olympic Valley, California.
- 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; 7:2816.
- Fishman JA, Rubin RH. Solid organ transplantation in HIV-infected individuals: obstacles and opportunities. Transplant Proc 2001; 33:1310.
- Heredia A, Margolis D, Oldach D, et al. Abacavir in combination with the inosine monophosphate dehydrogenase (IMPDH)-inhibitor mycophenolic acid is active against multidrug-resistant HIV-1. J Acquir Immune Defic Syndr 1999; 22:406.
- Steigbigel RT, Cooper DA, Kumar PN, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008; 359:339.
- Cooper DA, Steigbigel RT, Gatell JM, et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008; 359:355.
- Sax PE, DeJesus E, Mills A, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet 2012; 379:2439.
- DeJesus E, Rockstroh JK, Henry K, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet 2012; 379:2429.
- Raffi F, Rachlis A, Stellbrink HJ, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013; 381:735.
- Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med 2013; 369:1807.
- Bahirwani R, Barin B, Olthoff K, et al. Chronic kidney disease after liver transplantation in human immunodeficiency virus/hepatitis C virus-coinfected recipients versus human immunodeficiency virus-infected recipients without hepatitis C virus: results from the National Institutes of Health multi-site study. Liver Transpl 2013; 19:619.
- Bochet MR, Benhamou Y, et al. Tenofovir Disoproxil Fumarate Suppresses Lamivudine Resistant HBV Replication in Patients Co-Infected with HIV/HBV. 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Washington. Abstract 675.
- Gupta SK, Eustace JA, Winston JA, 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; 40:1559.
- Wyatt CM, Murphy B. Kidney transplantation in HIV-infected patients. Semin Dial 2005; 18:495.
- OUTCOMES BEFORE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
- Overview of medical literature
- SOLID ORGAN TRANSPLANTATION IN THE HAART ERA
- Liver transplantation
- Renal transplantation
- Heart transplantation
- CHEMOKINE RECEPTORS, TRANSPLANTATION, AND HIV INFECTION
- PHARMACOLOGIC ASPECTS AFTER TRANSPLANTATION
- VIRAL HEPATITIS RECURRENCE AFTER TRANSPLANTATION
- OTHER COMPLICATIONS AFTER SOLID ORGAN TRANSPLANTATION
- CURRENT TRANSPLANT ELIGIBILITY CRITERIA IN THE UNITED STATES
- SUMMARY AND RECOMMENDATIONS