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Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1
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sept 26 2023
Abstract
Introduction
Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE.
Methods
Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1-2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC). Endpoints included proportion with virologic response (HIV-1 RNA < 40 copies/mL, Snapshot), immunologic efficacy, and safety.
Results
At Week 240, 45% and 22% of the RC and NRC, respectively, had virologic response (Snapshot); 7% of the RC and 5% of the NRC had missing data due to coronavirus disease 2019 (COVID-19)-impacted visits. In the observed analysis, 82% of the RC and 66% of the NRC had virologic response. At Week 240, mean change from baseline in CD4+ T-cell count was 296 cells/mm3 (RC) and 240 cells/mm3 (NRC); mean CD4+/CD8+ ratio increased between Weeks 96 and 240 (RC 0.44 to 0.60; NRC 0.23 to 0.32). Between Weeks 96 and 240, four participants discontinued for adverse events, one additional participant experienced a drug-related serious adverse event, and six deaths occurred (median last available CD4+ T-cell count, 3 cells/mm3). COVID-19-related events occurred in 25 out of 371 participants; all resolved without incident.
Conclusion
Through ∼5 years, fostemsavir + OBT demonstrated durable virologic and immunologic responses with no new safety concerns between Weeks 96 and 240, supporting this regimen as a key therapeutic option for HTE people with multidrug-resistant HIV-1.
Immunologic Efficacy
In RC participants, mean CD4+ T-cell count increased from baseline through Week 192 and stabilized thereafter (observed analysis; Fig. 3A). CD4+ T-cell count also improved in NRC participants over time (mean change from baseline, 240 cells/mm3 at Week 240; observed analysis). Substantial improvements in CD4+ T-cell count were evident in all baseline CD4+ T-cell count subgroups but numerically greatest in those with < 20 cells/mm3 (mean [SD], 338 [250] cells/mm3) and 20 to < 50 cells/mm3 at baseline (332 [88] cells/mm3; Figure S3). By Week 240, 67% (22 of 33) of remaining participants with baseline CD4+ T-cell count < 20 cells/mm3 and 92% (12 of 13) with baseline CD4+ T-cell count 20 to < 50 cells/mm3 had CD4+ T-cell count ≥ 200 cells/mm3. Participants with baseline HIV-1 RNA ≥ 100,000 copies/mL and those with Week 240 HIV-1 RNA ≥ 40 copies/mL also demonstrated substantial mean increases (353 and 251 cells/mm3, respectively).
In the RC, mean (SD) CD4+/CD8+ ratio improved continuously, reaching 0.60 (0.39) at Week 240 (Fig. 3B). Of the RC participants, 60% (83 of 139) achieved CD4+/CD8+ ratio ≥ 0.45, including 47% (49 of 104 with available data) with baseline ratio < 0.3. CD4+/CD8+ ratio also continuously improved in the NRC, reaching a mean (SD) of 0.32 (0.25) by Week 240. Overall, 29% (9 of 31) of the NRC achieved CD4+/CD8+ ratio ≥ 0.45, including 16% (4 of 25 with available data) with baseline ratio < 0.3.
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