Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) has durable efficacy and differentiated safety compared to efavirenz/emtricitabine/tenofovir DF at week 96 in treatment-na ve 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 trial of elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) in treatment-naive 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. 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 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/mm 3 ) 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). 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 EFV/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 Zolopa A et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18219 http://www.jiasociety.org/index.php/jias/article/view/18219 | http://dx.doi.org/10.7448/IAS.15.6.18219