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:10.1007/s40121-023-00870-6

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

Infect Dis Ther. 2023 Sep;12(9):2321-2335. doi: 10.1007/s40121-023-00870-6. Epub 2023 Sep 26.

Authors

Judith A Aberg¹, Bronagh Shepherd², Marcia Wang³, Jose V Madruga⁴, Fernando Mendo Urbina⁵, Christine Katlama⁶, Shannon Schrader⁷, Joseph J Eron⁸, Princy N Kumar⁹, Eduardo Sprinz¹⁰, Margaret Gartland¹¹, Shiven Chabria¹², Andrew Clark¹³, Amy Pierce¹¹, Max Lataillade¹², Allan R Tenorio¹¹

Affiliations

¹ 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.
² GSK, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK.
³ GSK, 1250 S Collegeville Road, Collegeville, PA, 19426, USA.
⁴ CRT-DST/AIDS SP, Rua Santa Cruz 81, Vila Mariana, São Paulo, CEP: 04121-000, Brazil.
⁵ Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati 490, Jesús María, 15072, Peru.
⁶ Service de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Pitié-Salpêtrière, INSERM-Sorbonne Universités, 47-83 Bd de l'hôpital, 75013, Paris, France.
⁷ Schrader Clinic, 2211 Norfolk Street #1050, Houston, TX, 77098, USA.
⁸ University of North Carolina at Chapel Hill School of Medicine, 321 S Columbia Street, Chapel Hill, NC, 27599, USA.
⁹ Georgetown University Medical Center, 37th and O Street, N.W., Washington, DC, 20057, USA.
¹⁰ 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.
¹¹ ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA.
¹² ViiV Healthcare, 36 E Industrial Road, Branford, CT, 06405, USA.
¹³ ViiV Healthcare, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK.

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.

Keywords: Advanced HIV disease; Attachment inhibitor; CD4+/CD8+ ratio; CD4+ T-cell count; Virologic response.

Associated data

ClinicalTrials.gov/NCT02362503