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

Abstract

BACKGROUND\nA prespecified integrated safety analysis was conducted for 3 doravirine (DOR) double-blind trials (phase 2b: P007 [NCT01632345]; phase 3: DRIVE-FORWARD [NCT02275780] and DRIVE-AHEAD [NCT02403674]).\n\n\nMETHODS\nDOR (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.\n\n\nRESULTS\nDiscontinuation due to AEs was similar for participants on DOR and DRV+r (2.5% vs 3.1%), and lower for those on DOR than EFV (2.5% vs 6.6%). 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, treatment difference for discontinuations due to AEs was -3.4% favoring DOR (95% confidence interval: -6.2, -0.8; P=0.012). Fewer participants experienced neuropsychiatric AEs on DOR than EFV (25.0% vs 55.9%), and fewer experienced diarrhea on DOR than DRV+r (12.4% vs 22.5%). Change from baseline in most lipid parameters also favored DOR.\n\n\nCONCLUSIONS\nAt Week 48, DOR 100 mg had a favorable safety profile compared with EFV or DRV+r and a favorable tolerability profile compared with EFV.