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

Abstract

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‐naïve 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/μL and eGFR≥70 mL/min. Virologic success (HIV‐1 RNA <50 c/μL) at Week 96 was assessed per snapshot algorithm. Adverse events and laboratory data were collected prospectively. Bone mineral density (BMD) was assessed by DEXA scan in a subgroup of patients. Results: 708 patients (90% male, 74% white, 41% with HIV‐1 RNA >100,000 c/μL) 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/μL (82% vs 80%). Mean CD4 cell increases (cells/mm3) 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 (mmol/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.