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- Title
Once-daily Doravirine for Initial Treatment of Adults Living With Human Immunodeficiency Virus–1: An Integrated Safety Analysis.
- Authors
Thompson, Melanie; Orkin, Chloe; Molina, Jean-Michel; Sax, Paul; Cahn, Pedro; Squires, Kathleen; Xu, Xia; Rodgers, Anthony; Kumar, Sushma; Teppler, Hedy; Martin, Elizabeth; Hanna, George; Hwang, Carey
- Abstract
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.
- Subjects
COMBINATION drug therapy; COMPARATIVE studies; CONFIDENCE intervals; DIARRHEA; DRUG tolerance; DRUG side effects; HIV; HIV infections; HIV-positive persons; LIPIDS; PATIENT safety; TERMINATION of treatment; TREATMENT duration; ABACAVIR-lamivudine (Drug); DARUNAVIR; EMTRICITABINE-tenofovir; NON-nucleoside reverse transcriptase inhibitors; DESCRIPTIVE statistics; EFAVIRENZ; RITONAVIR; ADULTS
- Publication
Clinical Infectious Diseases, 2020, Vol 70, Issue 7, p1336
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciz423