A current focus in HIV management is improving adherence by minimizing pill burden with convenient formulations, including fixed-dose combinations (FDCs). Darunavir, a HIV protease inhibitor, co-administered with low-dose ritonavir (800/100 mg once daily), is recommended in guidelines in combination with other antiretrovirals for HIV patients with no darunavir resistance-associated mutations. Cobicistat is an alternative agent to ritonavir for boosting plasma drug levels of darunavir among other antiretrovirals. Cobicistat is a more specific cytochrome P450 3A inhibitor than ritonavir without enzyme-inducing properties. This review describes the differing effects of cobicistat and ritonavir on metabolic enzymes, which explains their differing drug-drug interactions, and summarizes some of the studied drug-drug interactions for cobicistat. It also outlines the clinical development and data for a once-daily darunavir/cobicistat FDC. This FDC thus allows for a once-daily treatment regimen (including background antiretrovirals) with reduced pill burden.
Keywords: HIV; cobicistat; darunavir; drug–drug interactions; efficacy; fixed-dose combination; pharmacokinetics; ritonavir; safety.