title: Darunavir/cobicistat once daily for the treatment of HIV.
abstract: 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.
authors.affiliation: Janssen Pharmaceutics, LLC, Titusville, NJ, USA.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: Herta
authors.initials: H
authors.lastname: Crauwels
authors.forename: Magda
authors.initials: M
authors.lastname: Opsomer
authors.forename: Frank
authors.initials: F
authors.lastname: Tomaka
authors.forename: Tom
authors.initials: T
authors.lastname: van de Casteele
authors.forename: Simon
authors.initials: S
authors.lastname: Vanveggel
authors.forename: Koen
authors.initials: K
authors.lastname: Iterbeke
authors.forename: Goedele
authors.initials: G
authors.lastname: de Smedt
mesh_terms: D002986:Clinical Trials as Topic; D000069547:Cobicistat / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000069454:Darunavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D017320:HIV Protease Inhibitors; D000069547:Cobicistat; D019438:Ritonavir; D000069454:Darunavir
keywords: HIV; cobicistat; darunavir; drug–drug interactions; efficacy; fixed-dose combination; pharmacokinetics; ritonavir; safety