The primary aim of this study is to evaluate the safety and efficacy of solid organ transplantation in people with HIV disease by conducting a prospective, multi-center cohort of HIV-positive (+) patients who undergo kidney o liver transplantation. Our long-range 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 antiretroviral (ARV) medications together, and (3) to understand underlying basic science mechanisms that explain patient outcomes so that clinical management can be adjusted to maximize the outcomes. Patients with HIV infection are at significant risk for end stage organ disease. Prior to the advent of highly active antiretroviral therapy (HAART), such patients were often not considered as transplant candidates based on poor prognosis. However, with the use of HAART, HIV positive patients have experienced significant improvements in morbidity and mortality. Thus, increasing numbers of HIV+ patients with end stage kidney and liver disease are potential candidates for transplantation. Despite increasing referrals, 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. Therefore, the primary clinical focus of this proposal is the design of a multi-center study that is powered to test the hypothesis that HIV+ liver and kidney transplant recipients will have patient and graft survival rates equivalent to other patient groups without HIV infection currently considered acceptable transplant candidates. In addition to providing the numbers required for a sufficiently powered study, the multicenter study provides access to 16 transplant centers for HIV+ patients facing end stage organ disease, facilitating regional access to avoid the logistic difficulties associated with limited access to distant sites. Of equal importance, the research plan establishes a prospective cohort that provides an ideal opportunity to explore mechanisms underlying disease progression in HIV+ transplant recipients and key issues in their medical management. The multi-center approach will capitalize on access to experts in the fields of virology and immunology. These investigators will explore the effects of immunosuppression (IS) on progression of HIV and viral co-pathogens known to be important in both transplant recipients and people with HIV infection. Progression of HIV and viral co-pathogens will be correlated with changes in the host immune response to HIV, viral co-pathogens, and allografts. These data will provide an essential contribution to an understanding of the factors that may be responsible for variations in graft and patient survival rates. This cohort will also provide the basis for describing the pharmacokinetic interactions between IS and the hepatically-metabolized ARVs, data that will greatly benefit health care workers managing HIV+ patients following transplantation, as maintaining appropriate levels of both of these classes of drugs will be essential for success.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI052748-07
Application #
7691335
Study Section
Special Emphasis Panel (ZRG1-AARR-2 (01))
Program Officer
Livnat, Daniella
Project Start
2003-08-15
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
7
Fiscal Year
2009
Total Cost
$2,581,879
Indirect Cost
Name
University of California San Francisco
Department
Surgery
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Ag├╝ero, F; Rimola, A; Stock, P et al. (2016) Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study. Am J Transplant 16:679-87
Roland, Michelle E; Barin, Burc; Huprikar, Shirish et al. (2016) Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls. AIDS 30:435-44
Balagopal, Ashwin; Barin, Burc; Quinn, Jeffrey et al. (2015) Immunologic Predictors of Liver Transplantation Outcomes in HIV-HCV Co-Infected Persons. PLoS One 10:e0135882
Stock, Peter G; Terrault, Norah A (2015) Human immunodeficiency virus and liver transplantation: Hepatitis C is the last hurdle. Hepatology 61:1747-54
Campos-Varela, Isabel; Straley, Stephanie; Agudelo, Eliana Z et al. (2015) Sofosbuvir, simeprevir, and ribavirin for the treatment of hepatitis C virus recurrence in human immunodeficiency virus/hepatitis C virus-coinfected liver transplant recipients. Liver Transpl 21:272-4
Frassetto, Lynda A; Tan-Tam, Clara C; Barin, Burc et al. (2014) Best single time point correlations with AUC for cyclosporine and tacrolimus in HIV-infected kidney and liver transplant recipients. Transplantation 97:702-7
Sherman, K E; Terrault, N; Barin, B et al. (2014) Hepatitis E infection in HIV-infected liver and kidney transplant candidates. J Viral Hepat 21:e74-7
Terrault, N; Reddy, K R; Poordad, F et al. (2014) Peginterferon and ribavirin for treatment of recurrent hepatitis C disease in HCV-HIV coinfected liver transplant recipients. Am J Transplant 14:1129-35
Stock, P G; Barin, B; Hatano, H et al. (2014) Reduction of HIV persistence following transplantation in HIV-infected kidney transplant recipients. Am J Transplant 14:1136-41
Stock, Peter G (2014) Kidney infection with HIV-1 following kidney transplantation. J Am Soc Nephrol 25:212-5

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