Aberg Judith A, Shepherd Bronagh, Wang Marcia, Madruga Jose V, Mendo Urbina Fernando, Katlama Christine, Schrader Shannon, Eron Joseph J, Kumar Princy N, Sprinz Eduardo, Gartland Margaret, Chabria Shiven, Clark Andrew, Pierce Amy, Lataillade Max, Tenorio Allan R
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.
GSK, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK.
Infect Dis Ther. 2023 Sep;12(9):2321-2335. doi: 10.1007/s40121-023-00870-6. Epub 2023 Sep 26.
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.
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.
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 (RC) and 240 cells/mm (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). COVID-19-related events occurred in 25 out of 371 participants; all resolved without incident.
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.
ClinicalTrials.gov, NCT02362503.
在3期BRIGHTE试验中，对附着抑制剂福沙匹韦+优化背景疗法（OBT）在经历过大量治疗（HTE）且当前抗逆转录病毒治疗方案失败的成人患者中进行了48周和96周的疗效和安全性评估。在此，我们报告了BRIGHTE试验中福沙匹韦+OBT在多药耐药人类免疫缺陷病毒（HIV）-1成人患者中的240周疗效和安全性。
经历过大量治疗且当前治疗方案失败的成人患者进入随机队列（RC；有1 - 2种完全有效的抗逆转录病毒药物）或非随机队列（NRC；没有完全有效的抗逆转录病毒药物），并接受开放标签的福沙匹韦+OBT（RC组从第8天开始，NRC组从第1天开始）。终点包括病毒学应答比例（HIV-1 RNA＜40拷贝/mL，快照检测）、免疫疗效和安全性。
在第240周时，RC组和NRC组分别有45%和22%的患者获得病毒学应答（快照检测）；RC组7%和NRC组5%的患者因2019冠状病毒病（COVID-19）影响访视而有缺失数据。在观察性分析中，RC组82%和NRC组66%的患者获得病毒学应答。在第240周时，CD4 + T细胞计数相对于基线的平均变化在RC组为296个细胞/mm，在NRC组为240个细胞/mm；CD4+/CD8 + 比值在第96周和第240周之间有所增加（RC组从0.44增至0.60；NRC组从0.23增至0.32）。在第96周和第240周之间，有4名参与者因不良事件停药，另外1名参与者发生了与药物相关的严重不良事件，还有6例死亡（最后一次可获得的CD4 + T细胞计数中位数为3个细胞/mm）。371名参与者中有25人发生了与COVID-19相关的事件；所有事件均顺利解决。
经过约5年时间，福沙匹韦+OBT显示出持久的病毒学和免疫学应答，在第96周和第240周之间没有新的安全问题，支持该方案作为HTE多药耐药HIV-1患者的关键治疗选择。
ClinicalTrials.gov，NCT02362503。
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