COBICISTAT Cytochrome P450 CYP3A Inhibitor Anti-HIV Agent

Highly active antiretroviral therapy (HAART) has converted HIV-AIDS from one of history's worst pandemics to a chronic disease. HAART is the combination of different families of drugs that inhibit various stages of the HIV life cycle. Among these drug families, the protease inhibitors have a low systemic exposure and short half-life after oral administration due to their rapid metabolism by cytochrome P450 3A (CYP3A) enzymes, which can be circumvented by the concomitant administration of ritonavir, a mechanism-based inhibitor of CYP3A enzymes. Cobicistat (GS-9350) is a novel pharmacoenhancer with no anti-HIV activity, which produces mechanism-based CYP3A inhibition similar to that of ritonavir, with better physicochemical properties that allow coformulation with antiretrovirals, reduced off-target drug interactions and improved tolerability. Phase II and III trials are currently assessing the safety and efficacy of cobicistat-boosted protease inhibitors or integrase inhibitors as fixed-dose combinations in a single tablet.