Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz Versus Combivir/Efavirenz in Antiretroviral-Naive HIV-1 Infected Subjects

The purpose of Study GS-01-934 was to assess the efficacy and safety of two simplified antiretroviral treatment (ART) regimens in ART-naive, human immunodeficiency virus, type 1 (HIV-1) infected participants. The primary objective of the study was to assess noninferiority of emtricitabine (FTC) and tenofovir disoproxil fumarate (tenofovir DF; TDF) in combination with efavirenz (EFV) relative to Combivir (CBV) in combination with EFV in the treatment of HIV-1 infected ART-naive participants, determined by the achievement and maintenance of confirmed HIV-1 ribonucleic acid (RNA) \< 400 copies/mL (c/mL) through Week 48, as defined by the United States (US) Food and Drug Administration (FDA) time-to-loss-of-virologic-response (TLOVR) algorithm.

This study was originally planned as a 48-week, Phase 3, randomized, open-label, multicenter study comparing EFV+FTC+TDF (administered as the individual component drugs) versus CBV (lamivudine/zidovudine) + EFV to assess the efficacy and safety of both treatments in ART-Naive, HIV-1 infected participants. The regimen of CBV (administered twice daily) + EFV (administered once daily) served as the active control treatment and was compared with the regimen of EFV+FTC+TDF; each component drug in the EFV+FTC+TDF regimen was administered once daily. Week 48 to Week 96: The study was extended and continued to evaluate the efficacy and safety of the two regimens up to a total treatment duration of 96 weeks. The regimen of EFV+FTC+TDF continued to be dosed as the component drugs (EFV + FTC + TDF), once daily, without regard to meals. The regimen of CBV+EFV was dosed as 2 pills (CBV, twice daily in the morning without regard to meals) + EFV (once daily, without regard to meals). Week 96 to Week 144: A further study extension changed the 3-pill EFV+FTC+TDF regimen to a 2-pill regimen of EFV + Truvada (\[TVD\]: a fixed-dose combination pill containing FTC/TDF), once daily without regard to meals, and continued to evaluate the efficacy and safety of the two regimens for a further 48 weeks up to a total study treatment duration of 144 weeks. The regimen of CBV+EFV continued to be dosed as 2 pills (CBV, twice daily in the morning without regard to meals) + EFV (once daily, without regard to meals). Week 144 to end of study (Week 240): A final study extension provided all study participants from both treatment regimens the option to switch their respective treatments to the 1-pill regimen of for a further 96 weeks up to a total study duration of 240 weeks (5 years) to further assess the efficacy and safety of ART regimen simplification. At sites in France, the study was extended by a further 48 weeks (Year 6) or until ATR became commercially available (whichever happened first); once ATR became commercially available in France participants were not required to complete the full 288 weeks of the study.