Dolutegravir/Lamivudine for Maintenance of Virological Suppression in Persons With Historical Suspected or Confirmed Resistance to Lamivudine: Week 48 Results of a Single-Arm, Open-Label, Multicenter, Phase IIa Clinical Trial

BACKGROUND: We investigated the efficacy of dolutegravir/lamivudine for maintenance treatment for people with human immunodeficiency virus (HIV, PWH) and previous lamivudine resistance. METHODS: Open-label, single arm, multicentric clinical trial including virologically suppressed PWH with historical lamivudine resistance (confirmed by genotypic testing or suspected based on clinical history), no integrase resistance and CD4+ >200 cells/mm3 whose antiretroviral therapy (ART) was changed to dolutegravir/lamivudine if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Proviral DNA next-generation sequencing (NGS) was retrospectively performed in baseline samples. Primary endpoint was proportion of participants with huma immunodeficiency virus type 1 (HIV-1) RNA viral load (VL) ≥50 copies/mL at 48 weeks in the intention-to-treat-exposed (ITT-e) population using the Food and Drug Administration snapshot algorithm. RESULTS: In total, 121 participants enrolled, 114 with a prior genotype with M184V/I, mean virological suppression of 9 years. And 24 (19.8%) had the M184V/I in baseline proviral DNA NGS (>5% threshold). At 48 weeks, 4 participants had a VL ≥50 copies/mL (3.3%, 95% confidence interval [CI]: ·.9%-8.2%, FDA-Snapshot ITT-e): 1 confirmed virologic withdrawal, 1 precautionary virologic withdrawal, and 2 discontinued from study treatment for other reasons with last VL ≥50 copies/mL; none had M184V/I in baseline proviral DNA NGS, and there was no emergent integrase resistance. Also, 90.1% participants (109/121) had a VL <50 copies/mL (95% CI: 83.3%-94.8%), and there were no data for 6.6% (8/121 participants) at 48 weeks. CONCLUSIONS: After excluding lamivudine mutations in proviral DNA by population sequencing, dolutegravir/lamivudine effectively maintained virological suppression in PWH with CD4+ >200 cells/mm3 and history of lamivudine resistance. Notably, no treatment-emergent resistance was observed.