Efficacy and safety of the HIV-1 maturation inhibitor GSK3640254 plus two NRTIs in adults naive to antiretroviral therapy (DOMINO): 24-week results from a randomised phase 2b study.
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- Record sourced from PubMed, PMID 41357330.
- Also identified by DOI 10.1016/j.eclinm.2025.103567 and PMC identifier 12675029.
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Abstract
There is an unmet need for antiretrovirals with novel mechanisms of action that can provide additional options for people with HIV-1. DOMINO evaluated the efficacy and safety of the maturation inhibitor GSK3640254 (GSK'254) plus two nucleoside reverse transcriptase inhibitors (NRTIs) in adults naive to antiretroviral therapy. This partially blinded, multicentre phase 2b trial enrolled people with HIV-1 from 54 centres in ten countries (Argentina, Canada, France, Germany, Italy, Portugal, Russian Federation, 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<sup>3</sup> who were naive to antiretroviral therapy. Participants were centrally randomised to receive once-daily oral GSK'254 100, 150, or 200 mg (double-blinded dose) or open-label dolutegravir (DTG) 50 mg, each with open-label NRTIs. The primary endpoint was proportion with Snapshot HIV-1 RNA <50 copies/mL at Week 24 (intention-to-treat-exposed population). Safety was assessed through Week 24. This trial is registered at ClinicalTrials.gov, NCT04493216 (trial closed). Screenings occurred between November 18, 2020, and January 31, 2022; 161 participants were randomised (sex assigned at birth: 24% female; 76% male). At Week 24, proportions with HIV-1 RNA <50 copies/mL were 83% (33/40), 91% (39/43), and 76% (32/42) in the GSK'254 100-mg, 150-mg, and 200-mg groups, respectively, vs 92% (33/36) in the DTG group. One participant receiving DTG and eight participants receiving GSK'254 had protocol-defined virologic failure (no resistance detected). All GSK'254 doses were generally well tolerated, with few participants reporting drug-related serious adverse events (GSK'254: 150 mg, 2% [1/43]; 200 mg, 2% [1/42]). GSK'254 plus two NRTIs demonstrated efficacy and safety with no treatment-emergent resistance, consistent with DTG plus two NRTIs, supporting potential further evaluation of maturation inhibitors. ViiV Healthcare.