HIV protease inhibitors: pharmacologic and metabolic distinctions

In the earlier era of nucleoside analogue antiretroviral therapy, considerations of pharmacologic drug-drug interactions were only a small factor in choosing optimal therapies for patients with HIV infection. However, pharmacologic considerations are critical for selecting and managing the current multiple-drug antiretroviral regimens that include one or more HIV protease inhibitors (HPIs). Each of the available HPIs, both those that are licensed and those still under investigation, has distinct pharmacokinetic and metabolic properties that result in different dosing regimens and potential for interactions with food and other drugs. Although drug interactions are usually considered undesirable, some of the drug interactions between HPIs have beneficial effects on drug levels and total drug exposure. The non-nucleoside reverse transcriptase inhibitors also interact with HPIs. This article briefly reviews pharmacokinetic and metabolic distinctions among the newer antiretroviral agents, especially HPIs, up to the end of 1997, including selected agents that are still under investigation. As current treatment guidelines emphasize, HIV/AIDS patients typically receive several drugs; therefore, the potential for drug interactions, particularly those mediated by the P450 system in patients receiving HPIs or non-nucleoside reverse transcriptase inhibitors or both, must be appreciated by all physicians who care for patients with HIV disease.