Boosting HIV Treatment Options: Good News, New Challenges

Abstract

Keywords. pharmacoenhancer; cobicistat; boosted PIs.For >15 years, ritonavir (RTV) has beenthe only pharmacokinetic enhancer (ie,booster) for human immunodeficiencyvirus (HIV) protease inhibitors. The de-velopment of cobicistat (COBI) promisesto provide an alternative to RTV withoutdirect antiviral effects of its own. COBI, apotent cytochrome P450 3A (CYP3A)inhibitor recently approved by the Foodand Drug Administration (FDA) for usein a single-tablet regimen of elvitegravir/COBI/emtricitabine(FTC)/tenofovir dis-oproxil fumarate (TDF), is currentlybeing studied in phase 3 trials as boosterof other antiretroviral drugs. In vitrostudies demonstrate that COBI, unlikeRTV, is a weak inhibitor for CYP2D6 anddoes not have inhibitory effects on otherCYP isoforms (ie, CYP1A2, CYP2C09,and CYP2c19), making pharmacologicinteractions more predictable [1]. COBIalso seems to have less impact than RTVon normal adipocyte functions, such aslipid accumulation and/or response toinsulin, which may offer the potential forfewer adverse biochemical effects relativeto RTV [2]. In addition, the better solu-bility of COBI allows creation of a tabletformulation and coformulations thatmight foster the availability of othersingle-tablet regimens.In this issue of the Journal, Gallantet al report the 48-week results of a studycomparing COBI with RTVas a pharma-coenhancer for atazanavir (ATV) plusFTC/TDF in 698 treatment-naive HIVtype 1 (HIV-1)–infected patients. Studysubjects were recruited in the UnitedStates, the Dominican Republic, Mexico,Thailand, Portugal, Germany, the UnitedKingdom, Italy, and Switzerland andwere randomly assigned in a 1:1 ratio toreceive COBI or RTV. Most of the partic-ipants (60%) were white, and similar toother large trials, the proportion ofwomen (17%) was low. Twenty-fourpercent reported Hispanic/Latino ethnic-ity. The studyallowed the inclusion of in-dividuals with active hepatitis, withhepatitis B present in 3.6% of patientsand hepatitisC in 5.3%. The immunolog-ic status of the patients was relativelygood, with 48% having CD4