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

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-naïve 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) 200 copies/mL) (p=0.47) or mean change from baseline VL (p=0.74). Mean change from baseline in CD4 T-cell counts at week 96 remained significantly higher for EFV400 than EFV600 (difference 25 cells/µL; 95% CI 2-48; p=0.03). There was no difference in the frequency or severity of AEs (EFV400 = 89.4%, EFV600 = 89.3%; difference 0.09; 95% CI -4.73 to 4.90; p=0.97). 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=0.01). SAEs did not differ in frequency (EFV400 = 7.5%, EFV600 = 10.4%; difference -2.9%; 95% CI -7.3 to 1.6; p=0.20). 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