Once-Daily Doravirine for Initial Treatment of Adults Living With HIV-1: An Integrated Safety Analysis

BACKGROUND: A prespecified integrated safety analysis was conducted for 3 doravirine (DOR) double-blind trials (Phase IIb: P007 [NCT01632345]; Phase III: DRIVE-FORWARD [NCT02275780] and DRIVE-AHEAD [NCT02403674]). METHODS: DOR (100 mg) arms from these trials were compared with darunavir plus ritonavir (DRV+r) in DRIVE-FORWARD and efavirenz (EFV) in P007 and DRIVE-AHEAD. Background therapies were emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in P007; abacavir/lamivudine (ABC/3TC) or FTC/TDF in DRIVE-FORWARD; and 3TC/TDF for DOR and FTC/TDF for EFV in DRIVE-AHEAD. The primary endpoint was the proportion of participants discontinuing due to adverse events (AEs) through Week 48. RESULTS: Discontinuation rates due to AEs were similar for participants on DOR and DRV+r (2.5% vs 3.1%, respectively) and lower for those on DOR than for those on EFV (2.5% vs 6.6%, respectively). Rates of drug-related AEs for DOR, DRV+r, and EFV were 30.9%, 32.1%, and 61.4%, respectively. In an analysis of DOR versus EFV, the treatment difference for discontinuations due to AEs was -3.4%, favoring DOR (95% confidence interval -6.2 to -0.8; P = .012). Fewer participants experienced neuropsychiatric AEs on DOR than on EFV (25.0% vs 55.9%, respectively), and fewer experienced diarrhea on DOR than on DRV+r (12.4% vs 22.5%, respectively). Changes from baseline in most lipid parameters also favored DOR. CONCLUSIONS: At Week 48, DOR at 100 mg had a favorable safety profile compared with EFV or DRV+r and a favorable tolerability profile compared with EFV. CLINICAL TRIALS REGISTRATION: NCT01632345; NCT02275780 and NCT02403674.