The FDA has approved the fixed-dose combination of elvitegravir/cobicistat/tenofovir/emtricitabine as a single-pill regimen for initial treatment of HIV-infected adults. Known as the "Quad" pill in casual parlance, this combination is branded as Stribild. The recommended dosage is 1 pill, once daily, taken with food.
The combination includes two new components, elvitegravir and cobicistat. Elvitegravir is an integrase inhibitor that is given once daily but requires pharmacokinetic boosting. Cobicistat is a pharmacokinetic enhancer of elvitegravir, and certain other drugs, but has no anti-HIV effect (unlike ritonavir). Interactions between the new agents and other drugs have not been well studied, but numerous interactions involving cobicistat in particular are possible, and the Stribild package insert contains a long list of cautions regarding potential interactions with numerous medications.
In Phase 3 studies, elvitegravir/cobicistat/tenofovir/emtricitabine generally was well tolerated. Cobicistat may increase serum creatinine (and decrease estimated GFR) via inhibition of tubular secretion of creatinine; it does not appear to affect actual GFR. This effect is small and stable over time. Having said that, the Quad coformulation also includes tenofovir, which has known nephrotoxicity and whose effects may be enhanced by cobicistat. The manufacturer cautions that this combination should not be initiated in persons with CrCl <70 mL/min, and should be discontinued in those with CrCl <50 mL/min. Other possible adverse effects of cobicistat include nausea and diarrhea.
The DHHS adult ARV treatment guidelines have been amended to include coformulated elvitegravir/cobicistat/tenofovir/emtricitabine as an "alternative" regimen for use in ART-naive persons with CrCl >70 mL/min.
Approval of elvitegravir and cobicistat as separate agents is under consideration. For further information, see the Stribild package label.