Drug interactions between antiretroviral drugs and comedicated agents

HIV-infected individuals usually receive a wide variety of drugs in addition to their antiretroviral drug regimen. Since both non-nucleoside reverse transcriptase inhibitors and protease inhibitors are extensively metabolised by the cytochrome P450 system, there is a considerable potential for pharmacokinetic drug interactions when they are administered concomitantly with other drugs metabolised via the same pathway. In addition, protease inhibitors are substrates as well as inhibitors of the drug transporter P-glycoprotein, which also can result in pharmacokinetic drug interactions. The nucleoside reverse transcriptase inhibitors are predominantly excreted by the renal system and may also give rise to interactions. This review will discuss the pharmacokinetics of the different classes of antiretroviral drugs and the mechanisms by which drug interactions can occur. Furthermore, a literature overview of drug interactions is given, including the following items when available: coadministered agent and dosage, type of study that is performed to study the drug interaction, the subjects involved and, if specified, the type of subjects (healthy volunteers, HIV-infected individuals, sex), antiretroviral drug(s) and dosage, interaction mechanism, the effect and if possible the magnitude of interaction, comments, advice on what to do when the interaction occurs or how to avoid it, and references. This discussion of the different mechanisms of drug interactions, and the accompanying overview of data, will assist in providing optimal care to HIV-infected patients.