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

Autor: Aberg JA; Division of Infectious Diseases Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1090, New York, NY, 10029, USA. judith.aberg@mssm.edu., Shepherd B; GSK, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK., Wang M; GSK, 1250 S Collegeville Road, Collegeville, PA, 19426, USA., Madruga JV; CRT-DST/AIDS SP, Rua Santa Cruz 81, Vila Mariana, São Paulo, CEP: 04121-000, Brazil., Mendo Urbina F; Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati 490, Jesús María, 15072, Peru., Katlama C; Service de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Pitié-Salpêtrière, INSERM-Sorbonne Universités, 47-83 Bd de l'hôpital, 75013, Paris, France., Schrader S; Schrader Clinic, 2211 Norfolk Street #1050, Houston, TX, 77098, USA., Eron JJ; University of North Carolina at Chapel Hill School of Medicine, 321 S Columbia Street, Chapel Hill, NC, 27599, USA., Kumar PN; Georgetown University Medical Center, 37th and O Street, N.W., Washington, DC, 20057, USA., Sprinz E; Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, R. Ramiro Barcelos, 2350 - Santa Cecília, Porto Alegre, RS, 90035-903, Brazil., Gartland M; ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA., Chabria S; ViiV Healthcare, 36 E Industrial Road, Branford, CT, 06405, USA., Clark A; ViiV Healthcare, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK., Pierce A; ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA., Lataillade M; ViiV Healthcare, 36 E Industrial Road, Branford, CT, 06405, USA., Tenorio AR; ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA.
Jazyk: angličtina
Zdroj: Infectious diseases and therapy [Infect Dis Ther] 2023 Sep; Vol. 12 (9), pp. 2321-2335. Date of Electronic Publication: 2023 Sep 26.
DOI: 10.1007/s40121-023-00870-6
Abstrakt: 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/mm 3 (RC) and 240 cells/mm 3 (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/mm 3 ). 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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