Efavirenz 400 mg daily remains non‐inferior to 600 mg: 96 week data from the double‐blind, placebo‐controlled ENCORE1 study

Abstract

Introduction: ENCORE1 compared the efficacy and safety of reduced versus standard dose efavirenz (EFV) with tenofovir/ emtricitabine (TDF/FTC) as first-line HIV therapy. The primary analysis at 48 weeks showed 400 mg EFV was safe and virologically non-inferior to 600 mg. This analysis explores over 96 weeks the durability of efficacy and safety. Materials and Methods: A multinational, double-blind, placebo-controlled, non-inferiority trial in treatment-nave HIV-positive adults randomized to TDF/FTC plus reduced (400 mg, EFV400) or standard dose (600 mg, EFV600) EFV. The difference between proportions of participants with plasma HIV RNA (VL) B200 log 10 copies/mL by intention-to-treat (ITT missing0failure) was compared using a non-inferiority margin of (10%. Non-inferiority was also examined in per protocol (PP) and non-completer 0 failure (NC 0F) populations. Adverse events (AEs) and serious adverse events (SAEs) were summarized by treatment arm. Results: The ITT population comprised 630 patients (EFV400 0 321; EFV600 0 309); 32% were female; 37%, 33% and 30% were African, Asian and Caucasian, respectively. A total of 585 (EFV400 0 299; EFV600 0 286) completed 96 weeks on randomized therapy. At 96 weeks, proportions with VL B200 copies/mL were EFV400 (90.0%) and EFV600 (90.6%) (difference (0.6; 95% CI (5.2 to 4.0; p 00.72) demonstrating continued non-inferiority. Non-inferior efficacy was also observed for VL thresholds of B50 and B400 copies/mL irrespective of baseline VL (B100,000 versus ]100,000 copies/mL). There was no between-arm difference in time to loss of virological response (200 copies/mL) (p00.47) or mean change from baseline VL (p 00.74). Mean change from baseline in CD4 T-cell counts at week 96 remained significantly higher for EFV400 than EFV600 (difference 25 cells/mL; 95% CI 2Á48; p00.03). There was no difference in the frequency or severity of AEs (EFV400 0 89.4%, EFV600 0 89.3%; difference 0.09; 95% CI (4.73 to 4.90; p 00.97). The proportions ever reporting an AE definitely or probably EFV-related were EFV400 (37.7%) and EFV600 (47.9%) (difference (10.2%; 95% CI (17.9 to (2.51; p 00.01). SAEs did not differ in frequency (EFV400 0 7.5%, EFV600 0 10.4%; difference (2.9%; 95% CI (7.3 to 1.6; p 00.20). Conclusions: Non-inferiority of EFV 400 mg to EFV 600 mg when combined with TDF/FTC as initial HIV therapy was confirmed at week 96. Both doses demonstrated similar safety profiles. These results support the use of a lower EFV dose as part of routine HIV management.