Department of Infectious Diseases, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Immunol. 2024 May 28;15:1394644. doi: 10.3389/fimmu.2024.1394644. eCollection 2024.
Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes.
The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm at any time during 48-week analysis periods through week 192.
Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm at any time vs those sustaining <200 cells/mm. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm.
Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment.
NCT02362503, https://clinicaltrials.gov/study/NCT02362503.
福斯特玛韦是一种 gp120 定向附着抑制剂，适用于多重耐药 HIV-1 的大量治疗经验（HTE）成人。我们提供 BRIGHTE 研究的详细 240 周安全性结果，并评估免疫恢复对安全性结果的影响。
正在进行的 3 期 BRIGHTE 试验；本分析的数据来自第一位参与者的首次就诊（2015 年 2 月 23 日）至最后一位参与者的最后一次就诊（2021 年 3 月 22 日）的第 240 周。接受福斯特玛韦+优化背景治疗的参与者评估了安全性终点。在基线 CD4+T 细胞计数<200 个/毫米的参与者中，在 48 周分析期的任何时间内，评估 CD4+T 细胞计数≥200 个/毫米的亚组中暴露调整后的不良事件（AE）发生率。
通过中位数 258 周（范围 0.14-319）的治疗，30/371（8%）名参与者因 AE 而停药。177/371（48%）名参与者报告了严重 AE，包括 13 名（4%）名参与者的 16 例药物相关事件。发生了 35 例（9%）死亡，主要与艾滋病或急性感染有关。25 例（7%）参与者发生了 COVID-19 相关事件；所有事件均无后遗症。在基线 CD4+T 细胞计数<200 个/毫米的参与者中，122/162（75%）在第 192 周达到 CD4+T 细胞计数≥200 个/毫米。在任何时候达到 CD4+T 细胞计数≥200 个/毫米的参与者中，暴露调整后的 AE 发生率明显低于维持<200 个/毫米的参与者。在 CD4+T 细胞计数≥200 个/毫米的参与者中，在第 48 周后未报告新的艾滋病定义事件。
BRIGHTE 240 周中期分析的累积安全性发现与其他 HTE 参与者中晚期 HIV-1 和合并症的试验一致。在接受福斯特玛韦治疗的免疫恢复参与者中，观察到艾滋病定义事件和 AE 的发生率降低。
NCT02362503，https://clinicaltrials.gov/study/NCT02362503。
Zotero 插件