In phase 3 BRIGHTE research, fostemsavir plus optimal background therapy (OBT) resulted in sustained rates of virologic suppression for 96 weeks in highly treated persons with multidrug-resistant HIV-1. About 163/272 (60%) Randomized Cohort (RC) patients (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants had HIV-1 RNA of fewer than 40 copies/mL (with 0 fully active antiretrovirals). The genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC individuals who satisfied protocol-defined virologic failure (PDVF) criteria through Week 96 were presented here. The incidence of PDVF in this difficult-to-treat patient population was as expected, and it was comparable among RC participants regardless of the presence of predefined gp120 amino acid substitutions that might influence phenotypic susceptibility to temsavir (S375H/I/M/N/T, M426L, M434I, M475I) or baseline temsavir 50% inhibitory concentration fold change (IC50 FC). Participants with a higher overall susceptibility score to newly used antiretrovirals (OSS-new) had a reduced incidence of PDVF, suggesting that OSS-new might be a better predictor of virologic outcomes in extensively treated patients. In 24/50 (48%) RC and 33/44 (75%) NRC subjects with PDVF, predefined gp120 alterations, most typically M426L or S375N, emerged on treatment with associated increases in temsavir IC50 FC. In the initial OBT of BRIGHTE, PDVF was not consistently linked with treatment-emergent genotypic or phenotypic alterations in temsavir or antiretroviral susceptibility. More research was needed in this extensively treated population to determine which factors were most likely to contribute to virologic failure.
Source:journals.asm.org/doi/10.1128/aac.01751-21
