Antiretroviral and Immunosuppressive Drug-Drug Interactions in Human Immunodeficiency Virus-Infected Liver and Kidney Transplant Recipients

Highly active antiretroviral therapy (HAART) has significantly reduced mortality, and prolonged life expectancy of human immunodeficiency virus (HIV)-positive patients. Such improvements have led to increasing numbers of HIV-infected patients with end-stage organ disease as potential candidates for transplantation. A HAART regimen usually consists of a combination of nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and/or protease inhibitors (PI). PI are known to strongly inhibit the cytochrome P450 3A (CYP3A) enzyme system that is responsible for the metabolism of immunosuppressive drugs, such as tacrolimus, sirolimus, and cyclosporine. Besides these pharmacokinetic drug-drug interactions, potential pharmacodynamic drug-drug interactions may also occur with concomitant HAART and antimetabolites, such as mycophenolate mofetil. An approach to immunosuppressive management in HIV-infected organ transplant recipients requires attention to such complexities as unique drug-drug interactions and increased drug-related toxicities.