Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
AIDS. 2010 Nov;24 Suppl 5:S29-36. doi: 10.1097/01.aids.0000391019.10661.66.
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%.
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.
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.
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.
我们描述了 ThibelaTB 中的异烟肼相关不良事件，这是南非一项针对矿区人群开展的社区范围异烟肼预防性治疗（IPT）的整群随机研究，该地区 HIV 感染率估计为 30%。
在开始 IPT 之前，同意参与的员工接受了活动性肺结核和异烟肼毒性增加风险的筛查，使用问卷和胸片进行评估。在每次研究访问时都寻找研究定义的 IPT 相关不良事件：仅在临床需要时进行肝功能检查。在一个子研究中，我们在基线和第 1、3 和 6 个月连续询问了参与者有关轻微 IPT 相关不良事件的情况。
在 24221 名参与者（95.2%为男性，中位年龄 40 岁）中，有 130 人发生了 132 例研究定义的不良事件（0.54%）；61 例（0.25%）可能为过敏疹，50 例（0.21%）周围神经病，17 例（0.07%）临床肝毒性，4 例（0.02%）癫痫发作。有 4 个事件（2 例肝毒性，1 例致命，2 例癫痫发作）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%比 0.03%，比值比 3.9（95%置信区间 1.2-12.1）]，但与性别、年龄、体重或同时接受抗逆转录病毒治疗无关。在子研究中，498 名参与者中的 324 名（65.1%）报告说，自开始接受 IPT 以来健康状况有所改善；324 名参与者中有 180 名（55.6%）表示，这是因为食欲增加。服用 IPT 的人群中特定轻微症状的频率较低，所有症状的报告频率均低于基线。
在该人群中，不良事件的风险，特别是肝毒性，非常低。我们的数据表明，在 IPT 之前和期间的筛查和监测中，可以安全地使用临床标准。
