Liver Transplants 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 ]
  

Procedure: Liver transplant
participants will receive donor livers
Drug: Immunosuppressive drugs
to prevent rejection of donor liver
Drug: Antirejection treatment
to prevent rejection of donor liver
Drug: Transplant- and HIV-related prophylaxis treatment
to prevent opportunistic infection
Drug: Tuberculosis prophylaxis treatment
to prevent TB

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:

1. Immunosuppression, with a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroids.
2. 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.
3. 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.
4. HIV- and transplant-related prophylaxis of Pneumocystis carinii pneumonia (PCP), by sulfamethoxazole/trimethoprim, dapsone, atovaquone, or pentamidine.
5. Vaccinations with pneumococcal vaccine polyvalent, hepatitis A and B virus vaccines (if not immune), and influenza vaccine prior to transplant.
6. 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.