Impact of Fostemsavir in Individuals with Multidrug-Resistant HIV-1, Stratified by Baseline Viral Load.

INTRODUCTION: In populations with undetectable or low viral load (VL) and limited treatment options, antiretrovirals with a new mechanism of action may support HIV-1 treatment success. We evaluated efficacy and safety of fostemsavir-based regimens in participants with limited treatment options and an undetectable or low baseline VL from the phase 3 BRIGHTE study. METHODS: BRIGHTE included adults with multidrug-resistant HIV-1 on failing regimens with ≤ 2 fully active antiretrovirals remaining. Participants with 1-2 fully active antiretrovirals entered the randomized cohort and received open-label fostemsavir + optimized background therapy after an 8-day placebo-controlled period. This post hoc analysis assessed virologic suppression (VL < 40 copies/mL; missing = excluded), immunologic outcomes, and safety through week 240 by baseline VL (< 40, 40 to < 400, 400 to < 1000, and ≥ 1000 copies/mL). RESULTS: In the randomized cohort (N = 272), 21 (8%) participants had baseline VL < 400 copies/mL, 2 with < 40 copies/mL. By week 24, 13/18 (72%), 8/10 (80%), and 121/219 (55%) participants in the < 400, 400 to < 1000, and ≥ 1000 copies/mL subgroups, respectively, had virologic suppression. At week 240, 14/14 (100%) participants with baseline VL < 400 copies/mL were suppressed. In the overall randomized cohort, CD4+ T cell count (P < 0.001) and CD4+/CD8+ ratio (P < 0.001) demonstrated a significant increase from baseline through week 240. Mean change from baseline to week 240 in CD4+ T cell count was + 294 and + 141 cells/mm3 in the < 40 and 40 to < 400 copies/mL subgroups, respectively. Mean CD4+/CD8+ ratio was 0.62 at baseline and 0.79 at week 240 in the < 40 copies/mL subgroup and 0.34 at baseline and 0.62 at week 240 in the 40 to < 400 copies/mL subgroup. Few adverse events leading to withdrawal/discontinuation were observed in the < 40 copies/mL (0/2) or 40 to < 400 copies/mL (1/19 [5%]) subgroups. CONCLUSION: Findings support considering fostemsavir for regimen optimization in individuals with limited treatment options and undetectable/low VL, especially if safety/tolerability may be a concern. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02362503.