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| Paper #101 Elvitegravir/Cobicistat/Emtricitabine/Tenofovir (Quad) Has Non-inferior Efficacy and Favorable Safety Compared to Efavirenz/Emtricitabine/Tenofovir in Treatment-naïve HIV-1+ Subjects Paul Sax*1, E DeJesus2, A Mills3, A Zolopa4, C Cohen5, D Wohl6, J Gallant7, H Liu8, E Quirk8, and B Kearney8 1Brigham and Women`s Hosp, Harvard Med Sch, Boston, MA, US; 2Orlando Immunology Ctr, FL, US; 3Anthony Mills MD, Inc, Los Angeles, CA, US; 4Stanford Univ, Palo Alto, CA, US; 5Community Res Initiative of New England, Boston, MA, US; 6Univ of North Carolina at Chapel Hill, US; 7Johns Hopkins Univ Sch of Med, Baltimore, MD, US; and 8Gilead Sci, Foster City, CA, US Background: The integrase inhibitor elvitegravir (EVG) has been co-formulated with the pharmacoenhancer cobicistat (COBI), emtricitabine (FTC), and tenofovir DF (TDF) in a single once-daily tablet (Quad). We report the week 48 results of a prospective, randomized, double-blind, active-controlled, ongoing Phase 3 trial comparing Quad with co-formulated efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) as initial therapy for HIV infection. Methods: Treatment-naïve subjects with HIV were randomized 1:1 to blinded Quad or EFV/FTC/TDF once daily plus matching placebos. Eligibility criteria included screening HIV RNA ≥ 5,000 copies/mL, CLCr ≥70 mL/min, and sensitivity to EFV, FTC, and TDF. Randomization was stratified by HIV-1 RNA > or ≤100,000 copies/mL. The 1˚ endpoint was the proportion of subjects with HIV RNA <50 copies/mL at week 48 per the FDA snapshot algorithm (12% pre-specified non-inferiority margin). Results: Seven hundred subjects (89% male, 37% non-white, 33% with viral load >100,000 copies/mL) were randomized and treated. The 1˚ endpoint was met; Quad was non-inferior to EFV/FTC/TDF with 88% and 84%, respectively, having viral suppression at week 48 by snapshot algorithm (difference +3.6%, 95%CI –1.6% to +8.8%). Among subjects with baseline HIV RNA >100,000 copies/mL, response rates were similar (Quad 84%, EFV/FTC/TDF 82%). Virologic failure rates at week 48 were 7% in both arms (FDA snapshot). At week 48, mean CD4 cell increase was 239 cells/μL in Quad and 206 cells/μL in EFV/FTC/TDF (p = 0.009). Drug discontinuation rates for adverse events (AE) were similar (Quad 3%, EFV/FTC/TDF 5%). Among AE occurring in ≥10% of subjects (all grades), nausea was significantly more frequent in Quad than EFV/FTC/TDF (21% vs 14%) while dizziness (7% vs 24%), abnormal dreams (15% vs 27%), insomnia (9% vs 14%), and rash (6% vs 12%) were significantly less common in Quad than EFV/FTC/TDF. CLCr decrease occurred by week 2 of Quad therapy and was significantly greater than with EFV/FTC/TDF (–14.3 vs –3.0 mL/min by week 48). Total cholesterol and LDL increases at week 48 were significantly lower for Quad than EFV/FTC/TDF. Conclusions: In this first Phase 3 study directly comparing once-daily single-tablet regimens for HIV, Quad demonstrated similarly high response rates compared to EFV/FTC/TDF and favorable CNS, rash, and fasting lipid results. These results suggest that Quad could become an important new option for initial HIV therapy. |