Infectious Diseases and Therapy (Sep 2023)

Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1

  • Judith A. Aberg,
  • Bronagh Shepherd,
  • Marcia Wang,
  • Jose V. Madruga,
  • Fernando Mendo Urbina,
  • Christine Katlama,
  • Shannon Schrader,
  • Joseph J. Eron,
  • Princy N. Kumar,
  • Eduardo Sprinz,
  • Margaret Gartland,
  • Shiven Chabria,
  • Andrew Clark,
  • Amy Pierce,
  • Max Lataillade,
  • Allan R. Tenorio

DOI
https://doi.org/10.1007/s40121-023-00870-6
Journal volume & issue
Vol. 12, no. 9
pp. 2321 – 2335

Abstract

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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. Trial registration ClinicalTrials.gov, NCT02362503.

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