Efavirenz 400 mg vs. 600 mg Combined with Lamivudine and Tenofovir in Treatment-Naïve HIV-Infected Patients in China: A Randomized, Multi-Centered, Controlled Trial

Abstract Background Optimizing efavirenz (EFV) dosing to minimize adverse events remains a critical issue. Studies indicate that reducing the EFV dose from 600 mg to 400 mg daily lowers side effect intensity while maintaining virological suppression. We previously showed that 600 mg daily EFV may lead to unnecessarily high exposure in Chinese patients, but the long-term efficacy and safety of dose reduction beyond 48 weeks in this population remain unknown. Methods We conducted a multicenter, randomized controlled trial comparing EFV 400 mg versus 600 mg, each combined with lamivudine (3TC) and tenofovir (TDF), in ART-naïve Chinese adults with HIV-1. The primary endpoint was virological suppression (HIV-RNA <50 copies/mL) at week 72. A total of 422 participants were randomized (215 in the 400 mg group, 207 in the 600 mg group); 334 (169 and 165, respectively) completed the week 72 primary endpoint assessment, while an optional extension to week 96 was conducted for exploratory analyses. Results At baseline, demographic and clinical characteristics were comparable between groups. At week 72, virological suppression (HIV-RNA <50 copies/mL) was achieved in 86.5% (186/215) of the EFV 400 mg group and 84.1% (174/207) of the EFV 600 mg group (difference +2.5 percentage points, 95% CI -4.3 to 9.2, p=0.57), meeting the non-inferiority criteria. While overall adverse event (AE) profiles were comparable, the EFV 600 mg group exhibited a significantly higher incidence of serious non-rash AEs (p=0.042), and a numerically higher but non-significant rate of drug discontinuation due to AEs (4.8% vs. 1.9%, p=0.094). Conclusions EFV 400 mg is non-inferior to EFV 600 mg in treatment-naïve Chinese patients over 72 weeks, offering improved safety and tolerability. Trial Registration #NCT04463784 on ClinicalTrials.gov (URL: https://clinicaltrials.gov/study/NCT04463784).