Efficacy and safety of the HIV-1 maturation inhibitor GSK3640254 plus dolutegravir as a two-drug regimen in adults naive to antiretroviral therapy (DYNAMIC): 24-week results from a randomised phase 2b study

作者：Samit R. Joshi, Mar Masiá, Essack Mitha, Antonella Castagna, Ezequiel Córdova, Moti Ramgopal, Alison Gaudion, S. Karthika, J Oyee, Veronica Bainbridge, Brian Wynne, Max Lataillade · 发表于：EClinicalMedicine · 年份：2025 · DOI：10.1016/j.eclinm.2025.103566 · 被引用次数：2 · 研究领域：HIV/AIDS drug development and treatment、HIV/AIDS Research and Interventions、HIV Research and Treatment

Background: There is an unmet need for two-drug antiretroviral regimens with novel mechanisms of action that can provide additional options for people with HIV-1. The DYNAMIC study evaluated the efficacy and safety of the maturation inhibitor GSK3640254 (GSK'254) plus dolutegravir (DTG) in adults naive to antiretroviral therapy. Methods: who were naive to antiretroviral therapy. Participants were centrally randomised to receive once-daily oral GSK'254 100 (N = 22), 150 (N = 20), or 200 mg (N = 22) or lamivudine (3TC) 300 mg (double-blinded dose) (N = 21), all with open-label DTG 50 mg. The primary endpoint was proportion of participants with Snapshot HIV-1 RNA <50 copies/mL at Week 24 (intention-to-treat-exposed population). Safety was assessed through Week 24 in participants who received study treatment. This trial is registered at ClinicalTrials.gov, NCT04900038 (trial closed). Findings: Screening occurred between Aug 18, 2021, and June 7, 2022; 85 participants were randomised (sex assigned at birth: 18% female; 82% male). At Week 24, proportions with HIV-1 RNA <50 copies/mL were 95% (21/22), 85% (17/20), and 77% (17/22) in the GSK'254 100-mg, 150-mg, and 200-mg groups, respectively, vs 86% (18/21) in the DTG plus 3TC group. Protocol-defined virologic failure occurred in the GSK'254 200-mg and DTG plus 3TC groups for one participant each. All GSK'254 doses were generally well tolerated, and no drug-related serious adverse events (AEs) or fatal AEs occurred. Interpretation: ...