Abstract
OBJECTIVES: The gp120-directed attachment inhibitor fostemsavir was effective in people with multidrug-resistant (MDR) HIV-1 in the BRIGHTE study. Understanding factors associated with virologic response can help clinicians optimize treatment and identify individuals for fostemsavir-based regimens. In previous multivariable analyses, baseline CD4+ T-cell count, baseline log(10) HIV-1 RNA and temsavir plasma concentration were associated with virologic response through 24 weeks. This expanded analysis evaluated predictors of the durability of response at Weeks 96 and 192. METHODS: BRIGHTE participant data (Randomized Cohort [RC], n = 272; Non-randomized Cohort, n = 99) were evaluated to examine baseline factors associated with virologic outcomes (HIV-1 RNA <40 copies/mL [Snapshot]; protocol-defined virologic failure [PDVF]) using linear/logistic regression with stepwise selection. A separate analysis evaluated baseline factors for association with treatment-adherent PDVF. RESULTS: In RC participants, higher baseline log(10) HIV-1 RNA, lower number of fully active available antiretrovirals in initial optimized background therapy (OBT) and a lower overall susceptibility score to newly used antiretrovirals in initial OBT were associated with lower odds of virologic response at Week 96. Baseline gp120 substitutions and dolutegravir use were additional factors through Week 192. Other baseline factors, including CD4+ T-cell count <20 cells/mm(3), HIV-1 RNA ≥100 000 copies/mL, antiretroviral therapy duration >20 years or gp120 substitutions, had low predictive value for treatment-adherent PDVF in RC participants (Week 96, 35%; Week 192, 39%). CONCLUSIONS: Multivariable analysis (MVA) identified several factors predictive of virologic response. No baseline factors were highly predictive of virologic failure at Weeks 96 or 192. Findings support the use of fostemsavir in diverse populations with MDR HIV-1.