Elvitegravir is an investigational integrase inhibitor that requires pharmacokinetic (PK) boosting. At the 16th Conference on Retroviruses and Opportunistic Infections (CROI) earlier this year, investigators presented 24-week data from a small randomized double-blind Phase 2 study of elvitegravir given with the investigational PK booster cobicistat (GS-9350) in combination with tenofovir/emtricitabine in initial therapy (also in this issue, see "Novel Pharmacokinetic Booster Cobicistat [GS-9350]"). All 4 medications were given in a 1-pill, once-daily coformulation known as the"Quad" pill. Patients in the comparator arm received efavirenz/tenofovir/emtricitabine (Atripla).
Forty-eight treatment-naive patients received elvitegravir/cobicistat (150/150 mg), and 23 received efavirenz. At 24 weeks, by an intention-to-treat (ITT) missing-equals-failure analysis, 90% of elvitegravir/cobicistat recipients and 83% of efavirenz recipients had HIV RNA levels of <50 copies/mL. The mean increase in CD4 count was 161 cells/µL for the elvitegravir/cobicistat group compared with 113 cells/µL for the efavirenz group.
Rates of adverse events were lower overall among recipients of elvitegravir/cobicistat (35% vs 57% for efavirenz), primarily owing to a lower rate of neuropsychiatric symptoms. Elvitegravir/cobicistat recipients, however, had greater decreases in estimated glomerular filtration rate (eGFR) (18 mL/min vs 7 mL/min) and higher rates of diarrhea (8% vs 4%).
Clinical Bottom Line
Longer-term follow-up of this study, and data from a larger number of subjects, are needed to define the efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir, but these interim results offer the possibility of an integrase inhibitor that can be dosed once daily and of an additional option for a 1-pill, once-daily combination regimen for use in initial therapy. As part of the next phases of investigation, the effects of cobicistat on renal function must be defined (see "Novel Pharmacokinetic Booster Cobicistat [GS-9350]" in this issue); specific studies of those effects and Phase 3 trials of the Quad regimen are under way.
- Cohen C, Shamblaw D, Ruane P, et al. Single-tablet, fixed-dose regimen of elvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS-9350 achieves a high rate of virologic suppression and GS-9350 is an effective booster. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 16-19, 2010; San Francisco. Abstract 58LB.