National Institute for Research in Tuberculosis, Chennai, India.
Stanley Medical College, Chennai, India.
JAMA Intern Med. 2018 Apr 1;178(4):485-493. doi: 10.1001/jamainternmed.2018.0141.
The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven.
To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB.
DESIGN, SETTING, AND PARTICIPANTS: This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016.
Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria.
The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens.
Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log10 copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/μL), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O'Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n = 4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence.
Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance.
clinicaltrials.gov Identifier: NCT00933790.
在接受抗逆转录病毒治疗的 HIV 阳性肺结核（TB）患者中，每日用药与每周三次用药方案相比的益处尚未得到证实。
比较每日、部分每日和间歇性抗结核治疗方案在治疗 HIV 相关性肺结核中的疗效和安全性。
设计、地点和参与者：这项开放标签、随机临床试验由印度南部国家结核病研究所进行。2009 年 9 月 14 日至 2016 年 1 月 18 日期间，招募了新诊断为、培养阳性、有肺部 TB 的感染 HIV 的成年人。
患者按基线 CD4 淋巴细胞计数和痰涂片等级分层，随机分配至每日、部分每日和间歇性抗结核治疗方案。抗逆转录病毒治疗按国家指南进行。每月对患者进行临床和痰微生物学检查，直到随机分组后 18 个月。使用标准标准记录不良事件。
主要结局是治疗反应良好，定义为治疗完成且最后 2 个月的所有可用痰培养均为结核分枝杆菌阴性。不良结局包括治疗失败、脱落、死亡和方案毒性。
331 名患者（251 名[76%]男性；平均[SD]年龄，39[9]岁；平均[SD]HIV 病毒载量，4.9[1.2]log10 拷贝/mL；中位数[四分位数间距]CD4 淋巴细胞计数，138[69-248]细胞/μL）中，每日、部分每日和间歇性方案的治疗反应良好分别为 91%（89/98）、80%（77/96）和 77%（75/98）。每日和间歇性方案之间的结局差异超过了 O'Brien-Fleming 组序贯边界，且获得性利福平耐药性（n=4）仅出现在间歇性方案中，数据安全监测委员会因此停止了该研究。3 种方案中，共有 18 名患者在治疗期间死亡，18 名患者脱落。每日、部分每日和间歇性方案中分别有 6、4 和 6 名患者出现 TB 复发。
在接受抗逆转录病毒治疗的 HIV 阳性肺结核患者中，每日抗结核方案在疗效和利福平耐药性的出现方面优于每周三次的方案。
clinicaltrials.gov 标识符：NCT00933790。
