[Drug interactions with antiretroviral agents]

Concomitant administration of three or more antiretroviral drugs is the standard treatment for HIV-infected patients. I.p. and NNRT are metabolized by cytochrome P450 and are inhibitors or inducers of CYP3A4. Therefore a number of drug-drug interactions are likely to occur. Ritonavir, a potent CYP3A4 inhibitor, is coadministered with saquinavir, indinavir and amprenavir to enhance their plasma concentrations and their virological efficacy. In contrast, nevirapine and efavirenz are CYP3A4 inducers, which warrant an increase in i.p. dosing. These properties lead to interactions with other drugs metabolized by CYP3A4 and a knowledge or the route of biotransformation is useful to avoid side-effects or decrease efficacy (as in the case of statine coadministration). Some important interactions can lead to contraindications such as coadministration of rifampicine, astemizole, ergot derivates or cizapride, as a large decrease or increase in concentration can lead to inefficacy or to major side-effects. Clinical trials and notification of side-effects are important to detect unpredictable interactions and to propose guidelines; such an example is therapeutic drug monitoring of methadone to avoid withdrawal syndrome when coadministered with ritonavir or nelfinavir.