Kidney and Liver Transplantation in People With HIV

• Subject survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
• graft survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

• Subject survival
• graft survival

• Opportunistic complications [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
• CD4+ T cell counts and HIV-1 RNA levels [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
• viral markers and host-response (CFC and ELISPOT) to viral co-pathogens, including HBV, HCV,CMV, EBV, HHV-6, HHV-8, and HPV [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
• rejection rates and markers of alloresponse [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
• pharmacokinetic interactions between immunosuppressive agents and antiretrovirals [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

• Opportunistic complications
• CD4+ T cell counts and HIV-1 RNA levels
• viral markers and host-response (CFC and ELISPOT) to viral co-pathogens, including HBV, HCV,CMV, EBV, HHV-6, HHV-8, and HPV
• rejection rates and markers of alloresponse
• pharmacokinetic interactions between immunosuppressive agents and antiretrovirals

With improved anti-HIV drug therapy, HIV infected patients are now living longer. These patients are at risk for liver and kidney failure and may need organ transplants. However, little is know about the safety and effectiveness of organ transplants in patients with HIV. This study will evaluate organ transplantation in HIV infected patients undergoing liver and kidney transplants.

HIV infected people are at significant risk for end stage organ disease. Prior to the advent of highly active antiretroviral therapy (HAART), these people were often not considered transplant candidates based on concern about potential adverse effects of immunosuppressive drugs on HIV disease progression. However, with the use of HAART, HIV infected people have experienced significant improvements in morbidity and mortality. HIV infected people with end stage kidney and liver disease are now potential candidates for transplantation, yet patients and clinicians lack the necessary data to determine the safety and efficacy of transplantation and immunosuppression in this group. This lack of conclusive data has led to continued denial of care by many transplant centers and third party payers, resulting in frustration and confusion for both patients and their health care providers.

This study will evaluate the safety and efficacy of solid organ transplantation in people with HIV infection by following a prospective, multi-center cohort of HIV infected people who undergo kidney or liver transplantation. The long-term goals are: 1) to provide patients and clinicians with information regarding the HIV-specific risks of transplantation; 2) to provide clinicians with information necessary to manage immunosuppressive and HAART medications together; and 3) to understand underlying basic science mechanisms that explain patient outcomes so that clinical management can be adjusted to improve outcomes.

Approximately 150 kidney and 125 liver transplant patients will be enrolled in this study over a 3-year period at medical research centers throughout the United States. Participants will be enrolled in the study for five years from the day of the transplant.

HIV-positive patients who undergo kidney or liver transplantation.

• HIV Infections
• Kidney Disease
• Liver Disease

• Carter JT, Melcher ML, Carlson LL, Roland ME, Stock PG. Thymoglobulin-associated Cd4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients. Am J Transplant. 2006 Apr;6(4):753-60.
• Frassetto L, Baluom M, Jacobsen W, Christians U, Roland ME, Stock PG, Carlson L, Benet LZ. Cyclosporine pharmacokinetics and dosing modifications in human immunodeficiency virus-infected liver and kidney transplant recipients. Transplantation. 2005 Jul 15;80(1):13-7.
• Roland ME, Carlson LL, Frassetto LA, Stock PG. Solid organ transplantation: referral, management, and outcomes in HIV-infected patients. AIDS Read. 2006 Dec;16(12):664-8, 675-8. Review.
• Roland ME, Stock PG. Liver transplantation in HIV-infected recipients. Semin Liver Dis. 2006 Aug;26(3):273-84. Review.
• Roland ME, Stock PG. Solid organ transplantation is a reality for patients with HIV infection. Curr HIV/AIDS Rep. 2006 Sep;3(3):132-8. Review.
• Terrault NA, Carter JT, Carlson L, Roland ME, Stock PG. Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation. Liver Transpl. 2006 May;12(5):801-7.
• Bihl FK, Loggi E, Chisholm JV 3rd, Hewitt HS, Henry LM, Linde C, Suscovich TJ, Wong JT, Frahm N, Andreone P, Brander C. Simultaneous assessment of cytotoxic T lymphocyte responses against multiple viral infections by combined usage of optimal epitope matrices, anti- CD3 mAb T-cell expansion and "RecycleSpot" J Transl Med. 2005 May 11;3(1):20.
• Frassetto LA, Browne M, Cheng A, Wolfe AR, Roland ME, Stock PG, Carlson L, Benet LZ. Immunosuppressant pharmacokinetics and dosing modifications in HIV-1 infected liver and kidney transplant recipients. Am J Transplant. 2007 Dec;7(12):2816-20. Epub 2007 Oct 19.
• Stock PG, Roland ME. Evolving clinical strategies for transplantation in the HIV-positive recipient. Transplantation. 2007 Sep 15;84(5):563-71.
• Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009 Oct;5(10):582-9. Review.
• Subramanian A, Sulkowski M, Barin B, Stablein D, Curry M, Nissen N, Dove L, Roland M, Florman S, Blumberg E, Stosor V, Jayaweera DT, Huprikar S, Fung J, Pruett T, Stock P, Ragni M. MELD score is an important predictor of pretransplantation mortality in HIV-infected liver transplant candidates. Gastroenterology. 2010 Jan;138(1):159-64. Epub 2009 Sep 30.
• Gasser O, Bihl F, Sanghavi S, Rinaldo C, Rowe D, Hess C, Stablein D, Roland M, Stock P, Brander C. Treatment-dependent loss of polyfunctional CD8+ T-cell responses in HIV-infected kidney transplant recipients is associated with herpesvirus reactivation. Am J Transplant. 2009 Apr;9(4):794-803.
• Coffin CS, Stock PG, Dove LM, Berg CL, Nissen NN, Curry MP, Ragni M, Regenstein FG, Sherman KE, Roland ME, Terrault NA. Virologic and clinical outcomes of hepatitis B virus infection in HIV-HBV coinfected transplant recipients. Am J Transplant. 2010 May;10(5):1268-75. Epub 2010 Mar 19.
• Tan-Tam CC, Frassetto LA, Stock PG. Liver and kidney transplantation in HIV-infected patients. AIDS Rev. 2009 Oct-Dec;11(4):190-204. Review.
• Stock PG, Barin B, Murphy B, Hanto D, Diego JM, Light J, Davis C, Blumberg E, Simon D, Subramanian A, Millis JM, Lyon GM, Brayman K, Slakey D, Shapiro R, Melancon J, Jacobson JM, Stosor V, Olson JL, Stablein DM, Roland ME. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med. 2010 Nov 18;363(21):2004-14.
• Ragni MV, Devera ME, Roland ME, Wong M, Stosor V, Sherman KE, Hardy D, Blumberg E, Fung J, Barin B, Stablein D, Stock PG. Liver transplant outcomes in HIV+ haemophilic men. Haemophilia. 2013 Jan;19(1):134-40. doi: 10.1111/j.1365-2516.2012.02905.x. Epub 2012 Jul 5.

Inclusion Criteria for All Participants:

• HIV infection
• Undetectable HIV viral load
• Meet all eligibility requirements for a transplant (same requirements that HIV uninfected patients must meet)
• Willing to take medication to prevent certain infections
• Willing to undergo frequent monitoring, including liver biopsies, and treatment, if participant has hepatitis B or C virus infection
• Willing to submit laboratory test results within 7 days of blood draw
• Willing to notify the transplant team before changing any medications
• If participant has a history of HIV-related cancers or opportunistic infections, some additional eligibility criteria must be met.

Inclusion Criteria for Patients Undergoing Kidney Transplant:

• CD4 count greater than 200 cells/mm3. CD4 count requirement for children will be based on child's age. Participant cannot have used the drugs IL-2 or GM-CSF in order to increase the CD4 count in the 6 months prior to transplant.

Inclusion Criteria for Patients Undergoing Liver Transplant:

• CD4 count greater than 100 cells/mm3. CD4 count requirement for children will be based on child's age. Some participants with certain HIV-related diseases must have a CD4 count that is greater than 200 cells/ml for the 6 months prior to study entry.

Exclusion Criteria for All Participants:

• Pregnancy
• Significant wasting or weight loss