Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.
Department of Global Health, University of Washington, Seattle, Washington, USA.
Clin Infect Dis. 2021 Jul 15;73(2):e337-e344. doi: 10.1093/cid/ciaa827.
Human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection.
We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-γ release assay (QuantiFERON-TB Gold Plus) and/or tuberculin skin test (TST, added 6 months after first participant exit).
Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287/298), and 88.9% (265/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28/265); 7.6% (10/132) in the INH arm and 13.5% (18/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24-1.14]; P = .11]), and driven primarily by TST positivity (8.6% [8/93] in INH and 18.1% [17/94] in no INH; relative risk, 0.48 [95% CI, .22-1.05]; P = .07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21/150] vs no INH, 10.7% [16/150]; P = .38), with no INH-related adverse events.
Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted.
NCT02613169.
在流行地区，人类免疫缺陷病毒（HIV）暴露但未感染（HEU）的婴儿患结核病（TB）的风险很高。对于婴儿来说，从原发性结核分枝杆菌（Mtb）感染到结核病的发展可能很快。我们评估了异烟肼（INH）是否预防原发性 Mtb 感染。
我们在肯尼亚进行了一项随机、非盲对照试验，纳入了 6 周龄无已知 TB 暴露的 HEU 婴儿。参与者按 1:1 随机分为 12 个月的每日 INH（10mg/kg）组与无 INH 组。主要终点是 12 个月时 Mtb 感染，通过干扰素-γ释放试验（QuantiFERON-TB Gold Plus）和/或结核菌素皮肤试验（TST，首次退出参与者后 6 个月添加）评估。
2016 年 8 月 15 日至 2018 年 6 月 6 日，共筛查了 416 名婴儿，其中 300 名（72%）随机分配至 INH 或无 INH 组（每组 150 名）；因 HIV 感染，2 名被排除。在 298 名随机 HEU 婴儿中，12 个月的保留率为 96.3%（287/298），88.9%（265/298）有主要结局数据。12 个月随访时 Mtb 感染率为 10.6%（28/265）；INH 组为 7.6%（10/132），无 INH 组为 13.5%（18/133）（每 100 人年 7.0 比 13.4；风险比，0.53 [95%置信区间 {CI}，.24-1.14]；P=0.11），主要由 TST 阳性驱动（INH 组为 8.6%[8/93]，无 INH 组为 18.1%[17/94]；相对风险，0.48 [95%CI，.22-1.05]；P=0.07）。INH 组与无 INH 组不良事件的严重程度相似（INH 组为 14.0%[21/150]，无 INH 组为 10.7%[16/150]；P=0.38），且无 INH 相关不良事件。
需要进一步研究评估结核预防治疗，以预防或延迟 HEU 和其他高危婴儿的原发性 Mtb 感染。
NCT02613169。
