Clinical Update: Impact of HIV Protease Inhibitors on the Treatment of HIV-Infected Tuberculosis Patients With Rifampin

IN 1995 and 1996, the Food and Drug Administration (FDA) approved three products in the new protease inhibitor class of drugs—saquinavir (Invirase^TM), ritonavir (Norvir^TM), and indinavir (Crixivan^TM). Another drug in this class of agents, nelfinavir (Viracept^TM) (Agouron Pharmaceuticals), is expected to be available soon from the manufacturer through an expandedaccess program. All four drugs, which inhibit HIV protease and thus interfere with viral maturation and replication, are the most potent antiretroviral agents available to treat patients with HIV disease. However, these protease inhibitors interact with rifamycin derivatives, such as rifampin and rifabutin, which are used to treat and prevent the mycobacterial infections commonly observed in HIV-infected patients. Rifamycins accelerate the metabolism of protease inhibitors (through induction of hepatic P450 cytochrome oxidases), resulting in subtherapeutic levels of the protease inhibitors. In addition, protease inhibitors retard the metabolism of rifamycins, resulting in increased serum levels of