Kidney Transplants in People With HIV Infection
The purpose of this study is to look at how kidney transplants and anti-rejection drugs affect the course of HIV disease and how HIV disease affects the success of kidney transplants. This study will also examine whether there are drug interactions between anti-rejection and anti-HIV drugs.
People with HIV are at an increased risk for kidney problems. If these problems get worse, the kidneys may stop working completely. One way to deal with this is a kidney transplant. Transplants often have not been done in HIV-infected people because the drugs needed to prevent rejection of the transplant were thought to worsen HIV disease. However, studies have shown that some anti-rejection drugs actually might slow HIV disease. This study will provide more information about kidney transplantation in people with HIV infection. It will also study whether anti-rejection drugs and anti-HIV drugs can be given together.
End-Stage Renal Disease
Other: Standard of Care Post-transplant Immunosuppression
Drug: Standard of Care Anti-retroviral Regimen for HIV Infection
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Clinical, Immunologic, and Pharmacologic Consequences of Kidney 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:||April 2001|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
Improvements in the treatment of HIV and survival of people with HIV have resulted in increasing numbers of HIV-infected patients dying from end stage organ disease rather than AIDS-associated opportunistic infections and neoplasms. Since HIV-infected people are at significant risk for End Stage Renal Disease, kidney transplantation is increasingly sought. People with HIV usually have been excluded from consideration for solid organ transplantation out of concern about potential adverse effects of immunosuppressive drugs on HIV disease progression. However, reviews of the long-term survival of HIV-positive transplant recipients without progression to AIDS suggest that certain immunosuppressive drugs may not only protect transplant recipients from the alloimmune response, but may decrease HIV disease progression. This "proof of principle" study evaluates the reciprocal impact of kidney transplantation and HIV infection. The compatibility of immunosuppressive and antiretroviral agents is also addressed.
Patients with end-stage kidney disease and HIV infection who meet both transplantation and study criteria are eligible for registration. After eligibility is determined, patients have CD4 T-cell and HIV-1 RNA assays performed every 2 months. Eligibility at the time of organ availability is determined based on the most recent CD4 T-cell count and viral load result, not more than 10 weeks prior to transplant. If eligible, patients are hospitalized for transplant and post-operative recovery. The following interventions are administered:
- Immunosuppression, with a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroids.
- Rejection treatment, if required, which may include sirolimus.
- HIV-related prophylaxis of toxoplasmosis, by Bactrim (sulfamethoxazole/trimethoprim), dapsone with pyrimethamine and leucovorin, or atovaquone with or without pyrimethamine and leucovorin; and of Mycobacterium avium complex, by azithromycin, clarithromycin, or rifabutin.
- Transplant-related prophylaxis of cytomegalovirus 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 Bactrim (sulfamethoxazole/trimethoprim), dapsone, atovaquone, or pentamidine. This is indicated in all patients for life.
- Vaccinations with Pneumovax, hepatitis A & B vaccines (if not immune), and influenza vaccine prior to transplant.
- Tuberculosis testing and prophylaxis, with PPD 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 6 inpatient, 14-hour clinic visits (screening, Week 2, Week 28, Week 52, Year 2, and Year 5), in addition to regular outpatient visits. Clinical evaluations and physical examinations at each clinic visit focus on signs and symptoms suggestive of HIV disease progression, impaired allograft function, and rejection. Clinical evaluation concentrates on symptoms and examination findings of the oropharynx, respiratory, cardiac, gastrointestinal, skin, lymphatic, and nervous system. Patients are screened for markers of opportunistic, hepatitis B, and hepatitis C infections. Immunology and pharmacology testing also is performed. CD4 T-cell, HIV-1 RNA, and standard laboratory tests are performed at each outpatient and clinic visit.
|United States, Maryland|
|Rockville, Maryland, United States, 20850|
|Principal Investigator:||Peter Stock, MD, PhD|