Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) has durable efficacy and differentiated safety compared to atazanavir boosted by ritonavir plus emtricitabine/tenofovir DF at week 96 in treatment-naïve HIV-1-infected patients

Purpose of the study : The primary Week 48 analysis of this ongoing, randomized, double-blind, double-dummy, active-controlled Phase 3 international trial of elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) in treatment-naive patients demonstrated that Quad was non-inferior to atazanavir boosted by ritonavir (ATV/r) + FTC/TDF with a differentiated safety profile. We report the Week 96 interim data. Methods : Key eligibility criteria included HIV-1 RNA ≥5,000 c/mL and eGFR ≥70 mL/min. Virologic success (HIV-1 RNA 100,000 c/mL) were randomized and treated. At Week 48, Quad was non-inferior to ATV/r + FTC/TDF (90% vs 87%, difference 3.0%, 95% CI -1.9% to 7.8%). High rates of virologic success were maintained at Week 96 (83% vs 82%, difference 1.1%, 95% CI -4.5% to 6.7%). Subgroup analysis revealed similar rates of virologic success in patients with baseline HIV-1 RNA >100,000 c/mL (82% vs 80%). Mean CD4 cell increases (cells/mm 3 ) were 256 vs 261 at Week 96. Emergent resistance was infrequent (2% vs <1%). Rates of study drug discontinuation due to adverse events (AEs) were low and comparable (4% vs 6%). Rates of study drug discontinuation due to renal reasons remained low and similar through Week 96 (3 [0.8%] vs 2 [0.6%]); since Week 48, 1 patient in each group discontinued study drug due to serum creatinine (Cr) increase without features of proximal renal tubulopathy. Median increases from baseline in serum Cr (μmol/L [mg/dL]) in Quad vs ATV/r + FTC/TDF at Week 96 (10.6 vs 7.1 [0.12 vs 0.08]) were similar to those at Week 48 (10.6 vs 7.1 [0.12 vs 0.08]). Quad continued to have smaller increases (mmol/L [mg/dL]) in triglycerides (0.06 vs 0.18 [5 vs 16], P=0.012); Quad had greater increases in total cholesterol (0.36 vs 0.21 [14 vs 8], P=0.046) at Week 96 only; changes in LDL and HDL cholesterol were similar. Quad had smaller mean decreases (%) in BMD (hip: -3.16 vs -4.19, P=0.069, spine: -1.96 vs -3.54, P=0.049). Conclusions : At Week 96, Quad demonstrated high rates of virologic suppression with low rates of resistance and a differentiated safety and tolerability profile relative to ATV/r + FTC/TDF. These results support the durable efficacy and long-term safety of Quad in HIV-1 infected patients. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Rockstroh J et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18220 http://www.jiasociety.org/index.php/jias/article/view/18220 | http://dx.doi.org/10.7448/IAS.15.6.18220