Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study

Background Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1.Methods CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening. No formal statistical analyses were performed.Results Among 272 participants, increases were observed from baseline to week 96 in CD4+ T-cell count (mean increase, +205 cells/mm3) and CD4+/CD8+ ratio (mean increase, +0.24). The proportion of observed participants with a CD4+/CD8+ ratio >= 0.45 increased from 9% (25/272) at baseline to 40% (85/213) at week 96. From baseline to week 96, we also observed trends toward decreases in the following (mean [SD] change): soluble CD14, -738.2 (981.8) mu g/L; soluble CD163, -138.0 (193.4) mu g/L; and D-dimer, -0.099 (0.521) mg/L fibrinogen-equivalent units. Decreases in biomarkers were generally observed among subgroups by baseline disease characteristics, virologic response, and CD4+ T-cell count.Conclusions These data suggest that heavily treatment-experienced persons with multidrug-resistant HIV-1 treated with fostemsavir + optimized background therapy may have improvements in immune parameters, including markers of monocyte activation and coagulopathy.Clinical Trials Registration NCT02362503 (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT02362503). In the phase 3 BRIGHTE study, heavily treatment-experienced adults with multidrug-resistant HIV-1 had robust improvements in immune parameters and markers of monocyte activation and coagulopathy through 96 weeks of fostemsavir-based therapy, regardless of baseline disease characteristics and virologic response.