Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) has durable efficacy and differentiated safety compared to efavirenz/emtricitabine/tenofovir DF at week 96 in treatment‐naïve HIV‐1‐infected patients

Abstract

Purpose of the studyThe primary Week 48 analysis of this ongoing, randomized, double‐blind, double‐dummy, active‐controlled Phase 3 trial of elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) in treatment‐naïve patients demonstrated that Quad was non‐inferior to efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) with a differentiated safety profile. We report the Week 96 interim data.MethodsKey eligibility criteria included HIV‐1 RNA ≥5,000 c/mL and eGFR ≥70 mL/min. Virologic success (HIV‐1 RNA <50 c/mL) at Week 96 was assessed per snapshot algorithm. Adverse events and laboratory data were collected prospectively.Results700 patients (89% male, 63% white, 33% with HIV‐1 RNA >100,000 c/mL) were randomized and treated. At Week 48, Quad was non‐inferior to EFV/FTC/TDF (88% vs 84%, difference +3.6%, 95% CI ‐1.6% to 8.8%). High rates of virologic success were maintained at Week 96 (84% vs 82%, difference 2.7%, 95% CI ‐2.9% to 8.3%). Subgroup analysis revealed similar rates of virologic success in patients with baseline HIV‐1 RNA >100,000 c/mL (81% vs 83%). Mean CD4 cell increase (cells/mm3) was 295 vs 273. Emergent resistance was infrequent (3% vs 3%). Rates of study drug discontinuation due to adverse events (AEs) were low and comparable (5% vs 7%). Rates of neuropsychiatric AEs were lower in Quad than in EFV/FTC/TDF (47% vs 66%, P<0.001), as were rates of rash (21% vs 31%, P=0.006). Drug discontinuation due to renal reasons occurred in 7 (2%) vs 0 patients through Week 96; only two patients discontinued Quad since Week 48 due to serum creatinine (Cr) increase without features of proximal renal tubulopathy. Median changes in serum Cr (µmol/L [mg/dL]) at Week 96 in Quad vs EFV/FTC/TDF (11.5 vs 0.9 [0.13 vs 0.01]) were similar to those at Week 48 (12.4 vs 0.9 [0.14 vs 0.01]). Quad had smaller median increases (mmol/L [mg/dL]) in total (0.23 vs 0.47 [9 vs 18], P<0.001) and LDL cholesterol (0.23 vs 0.41 [9 vs16], P=0.011), and similar increase in triglycerides (0.05 vs 0.09 [4 vs 8], P=0.41).ConclusionsAt Week 96, Quad demonstrated high rates of virologic suppression with low rates of resistance and a differentiated safety and tolerability profile relative to EFV/FTC/TDF. These results support the durable efficacy and long‐term safety of Quad in HIV‐1 infected patients.