Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
UCSF Center for Tuberculosis, University of California San Francisco, San Francisco, California, USA.
Clin Infect Dis. 2023 Feb 8;76(3):e580-e589. doi: 10.1093/cid/ciac707.
Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 noninferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the prespecified subgroup of people with human immunodeficiency virus (HIV) (PWH).
PWH and CD4+ counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months after randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% noninferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV status. PWH were enrolled in a staged fashion to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz.
A total of 2516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4+ count was 344 cells/μL (interquartile range: 223-455). The rifapentine-moxifloxacin regimen was noninferior to control (absolute difference in unfavorable outcomes -7.4%; 95% confidence interval [CI] -20.8% to 6.0%); the rifapentine regimen was not noninferior to control (+7.5% [95% CI, -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%).
In people with HIV-associated DS-PTB with CD4+ counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was noninferior to the 6-month control regimen and was safe.
NCT02410772.
结核病（TB）试验联合会研究 31/艾滋病临床试验组 A5349 是一项国际性随机开放标签 3 期非劣效性试验，结果表明，与标准的 6 个月疗程相比，用利福喷丁替代利福平、莫西沙星替代乙胺丁醇的 4 个月每日方案治疗药物敏感性肺结核（DS-PTB）在疗效方面不劣效，且安全。我们对预先设定的人类免疫缺陷病毒（HIV）（PWH）亚组人群的结果进行了探讨。
如果 PWH 的 CD4+计数≥100 个细胞/μL，并且正在接受或即将开始基于依非韦伦的抗逆转录病毒治疗（ART），则有资格入组。主要终点是随机分组后 12 个月时的结核病无病生存（疗效）和治疗期间≥3 级不良事件（AE）（安全性），疗效的非劣效性边界为 6.6%。随机分组按地点、肺空洞和 HIV 状况进行分层。PWH 分阶段入组，以支持对利福喷丁和依非韦伦之间药物相互作用的谨慎评估。
来自撒哈拉以南非洲、亚洲和美洲 13 个国家的 2516 名参与者符合条件。在 194 名（8%）微生物学合格的 PWH 中，中位 CD4+计数为 344 个细胞/μL（四分位间距：223-455）。利福喷丁-莫西沙星方案不劣于对照组（不良结局的绝对差异-7.4%；95%置信区间[CI] -20.8%至 6.0%）；利福喷丁方案不劣于对照组（+7.5%；95%CI -7.3%至 22.4%）。基于利福喷丁的方案报告的不良事件较少（15%），而对照组为 21%。
在基于依非韦伦的 ART 时 CD4+计数≥100 个细胞/μL 的 HIV 相关 DS-PTB 人群中，4 个月每日利福喷丁-莫西沙星方案与 6 个月对照方案相比不劣效，且安全。
NCT02410772。
