Liver Transplants in People With HIV Infection
HIV infected people are at increased risk for liver disease and failure, leading to the need for a liver transplant. Many HIV infected people are refused a transplant because it has been hypothesized that the antirejection drugs given to transplant patients would worsen HIV disease. Recent studies have shown that these drugs may actually slow HIV progression. The purpose of this study is to determine how liver transplant and antirejection drugs affect HIV progression and how HIV affects liver transplant survival.
Procedure: Liver transplant
Drug: Immunosuppressive drugs
Drug: Antirejection treatment
Drug: Transplant- and HIV-related prophylaxis treatment
Drug: Tuberculosis prophylaxis treatment
|Study Design:||Time Perspective: Prospective|
|Official Title:||Clinical, Immunologic, and Pharmacologic Consequences of Liver Transplantation in People With HIV Infection|
- Patient survival [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Graft survival [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Incidence of opportunistic infections [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Pharmacokinetic interactions between immunosuppressive agents and ARV agents [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
|Study Start Date:||January 2005|
|Primary Completion Date:||May 2007 (Final data collection date for primary outcome measure)|
Procedure: Liver transplant
Improvements in HIV treatment and survival of HIV infected people have resulted in increasing numbers of HIV infected patients dying from end-stage organ disease rather than AIDS-associated opportunistic infections and cancers. People with HIV have usually been excluded from consideration for solid organ transplantation out of concern about potential adverse effects of immunosuppressive drugs on HIV disease progression. However, data on the long-term survival of HIV infected transplant recipients without progression to AIDS suggest that certain immunosuppressive drugs may not only promote transplant survival but may slow HIV disease progression. This study will evaluate the impact of liver transplantation on HIV infection and vica versa. The interactions between immunosuppressive and antiretroviral drugs will also be addressed.
Patients with end-stage liver disease and HIV infection who meet both transplantation and study criteria are eligible for this study. While waiting for a liver to become available, patients will have CD4 counts and viral load checked every 2 months. Eligibility at the time of organ availability is determined based on the most recent CD4 count and viral load not more than 10 weeks prior to transplant. If eligible, patients will be hospitalized for transplant and postoperative recovery. The following interventions will be administered:
- Immunosuppression, with a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroids.
- Rejection treatment with sirolimus, if required. HIV-related prophylaxis of toxoplasmosis, by sulfamethoxazole/trimethoprim, dapsone with pyrimethamine and leucovorin, or atovaquone with or without pyrimethamine and leucovorin; and of Mycobacterium avium complex (MAC), by azithromycin, clarithromycin, or rifabutin.
- Transplant-related prophylaxis of cytomegalovirus (CMV) and/or herpes simplex virus, by acyclovir or ganciclovir; of Epstein-Barr virus, by ganciclovir; and of candidiasis, by Mycelex troches or fluconazole.
- HIV- and transplant-related prophylaxis of Pneumocystis carinii pneumonia (PCP), by sulfamethoxazole/trimethoprim, dapsone, atovaquone, or pentamidine.
- Vaccinations with pneumococcal vaccine polyvalent, hepatitis A and B virus vaccines (if not immune), and influenza vaccine prior to transplant.
- Tuberculosis (TB) testing and prophylaxis, with TB testing at screening and every 6 months; and prophylaxis following a previous or current reaction, by isoniazid and pyridoxine, rifampin and pyrazinamide, rifabutin and pyrazinamide, or rifampin alone.
During the study, patients have at least six inpatient, 14-hour clinic visits at screening, Week 2, Week 28, Week 52, Year 2, and Year 5, in addition to regular outpatient visits. Clinical evaluations and physical exams at each clinic visit focus on signs and symptoms suggestive of HIV disease progression, impaired transplant function, and rejection. Patients are screened for markers of opportunistic, and hepatitis B and C virus infections. Blood collection will occur at each outpatient clinic visit.
|Principal Investigator:||Peter Stock, MD, PhD||University of California, San Francisco|
|Principal Investigator:||Michelle Roland, MD||University of California, San Francisco|