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.

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: This double-blind, multicentre, phase 2b study enrolled participants from 39 centres in ten countries (Argentina, Canada, France, Germany, Italy, Portugal, Puerto Rico, South Africa, Spain, and the United States). Eligible participants were adults with plasma HIV-1 RNA ≥1000 copies/mL and CD4+ T-cell count ≥250 cells/mm 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: GSK'254 plus DTG demonstrated generally comparable efficacy and safety to DTG plus 3TC, supporting potential further evaluation of maturation inhibitors for HIV-1 treatment. Funding: ViiV Healthcare.