Adverse events with isoniazid preventive therapy: experience from a large trial
Adverse events with isoniazid preventive therapy: experience from a large trial
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DOI：
10.1097/01.aids.0000391019.10661.66
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发表时间：
2010-11-01
期刊：
影响因子：
3.8
通讯作者：
Churchyard, Gavin J.
中科院分区：
文献类型：
--
作者：
Grant, Alison D.;Mngadi, Kathryn T.;Churchyard, Gavin J.
目的：我们描述了 Thibela TB 中与异烟肼相关的不良事件，这是一项针对南非金矿工人进行社区范围异烟肼预防性治疗 (IPT) 的整群随机研究，南非的艾滋病毒感染率估计为 30%。 方法：在 IPT 之前，使用问卷和胸片对同意的员工进行活动性结核病和异烟肼中毒风险增加的筛查。每次研究访视时都会寻找研究定义的 IPT 相关不良事件：仅在有临床指征时才进行肝功能测试。在一项子研究中，我们在基线以及第 1、3 和 6 个月对连续参与者询问了与 IPT 相关的轻微不良事件。结果：在 24 221 名参与者中（95.2% 为男性，中位年龄 40 岁），有 130 人发生了 132 起研究定义的不良事件（0.54%）； 61 例（0.25%）可能出现过敏性皮疹，50 例（0.21%）周围神经病变，17 例（0.07%）临床肝毒性，以及 4 例（0.02%）惊厥。四个事件（两个肝毒性、一个致命事件和两个抽搐）符合严重性标准。临床肝毒性与饮酒有关[如果不饮酒则为0.11% vs. 0.03%，优势比为3.9（95%置信区间1.2-12.1）]，但与性别、年龄、体重或同时进行的抗逆转录病毒治疗无关。在该亚研究中，498 名参与者中有 324 名 (65.1%) 报告自开始 IPT 以来健康状况有所改善； 324 人中有 180 人（55.6%）表示这是因为食欲增加。接受 IPT 的患者中，特定轻微症状的发生率较低，并且所有症状的报告频率都低于基线。结论：该人群中不良事件（尤其是肝毒性）的风险非常低。我们的数据表明，临床标准可以安全地用于 IPT 之前的筛查和 IPT 期间的监测。 (C) 2010 年 Wolters Kluwer Health 垂直条 Lippincott Williams & Wilkins
Objectives: We describe isoniazid-related adverse events in Thibela TB, a cluster-randomized study of community-wide isoniazid preventive therapy (IPT) among gold miners in South Africa, where HIV prevalence is estimated at 30%.Methods: Consenting employees were screened prior to IPT for active tuberculosis and increased risk of isoniazid toxicity using a questionnaire and chest radiograph. Study-defined IPT-related adverse events were sought at each study visit: liver function tests were only performed if clinically indicated. In a substudy, we questioned consecutive participants at baseline and months 1, 3, and 6 concerning minor IPT-related adverse events.Results: Among 24 221 participants (95.2% men, median age 40 years), 130 individuals had 132 study-defined adverse events (0.54%); 61 (0.25%) possible hypersensitivity rash, 50 (0.21%) peripheral neuropathy, 17 (0.07%) clinical hepatotoxicity, and four (0.02%) convulsions. Four events (two hepatotoxicity, one fatal, and two convulsions) fulfilled criteria for seriousness. Clinical hepatotoxicity was associated with consumption of alcohol [0.11 vs. 0.03% if no alcohol consumed, odds ratio 3.9 (95% confidence interval 1.2-12.1)], but not with sex, age, weight, or concurrent antiretroviral therapy. In the substudy, 324 of 498 (65.1%) participants reported better health since starting IPT; 180 of 324 (55.6%) reported that this was because of increased appetite. The frequency of specific minor symptoms was low among those taking IPT, and all symptoms were reported less often than at baseline.Conclusion: The risk of adverse events, particularly hepatotoxicity, was very low in this population. Our data suggest that clinical criteria can safely be used for screening prior to and monitoring during IPT. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins