Zar Heather J, Cotton Mark F, Strauss Stanzi, Karpakis Janine, Hussey Gregory, Schaaf H Simon, Rabie Helena, Lombard Carl J
School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, South Africa.
BMJ. 2007 Jan 20;334(7585):136. doi: 10.1136/bmj.39000.486400.55. Epub 2006 Nov 3.
To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV.
Two centre prospective double blind placebo controlled trial.
Children aged > or =8 weeks with HIV.
Isoniazid or placebo given with co-trimoxazole either daily or three times a week.
Two tertiary healthcare centres in South Africa.
Mortality, incidence of tuberculosis, and adverse events.
Data on 263 children (median age 24.7 months) were available when the data safety monitoring board recommended discontinuing the placebo arm; 132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartile range 2.0-9.7) months. Mortality was lower in the isoniazid group than in the placebo group (11 (8%) v 21 (16%), hazard ratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) by intention to treat analysis. The benefit applied across Centers for Disease Control clinical categories and in all ages. The reduction in mortality was similar in children on three times a week or daily isoniazid. The incidence of tuberculosis was lower in the isoniazid group (5 cases, 3.8%) than in the placebo group (13 cases, 9.9%) (hazard ratio 0.28, 0.10 to 0.78, P=0.005). All cases of tuberculosis confirmed by culture were in children in the placebo group.
Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV. Prophylaxis may offer an effective public health intervention to reduce mortality in such children in settings with a high prevalence of tuberculosis.
Clinical Trials NCT00330304.
研究异烟肼预防治疗对感染人类免疫缺陷病毒（HIV）儿童死亡率和结核病发病率的影响。
两中心前瞻性双盲安慰剂对照试验。
年龄≥8周的HIV感染儿童。
异烟肼或安慰剂与复方新诺明联合使用，每日一次或每周三次。
南非的两家三级医疗中心。
死亡率、结核病发病率和不良事件。
当数据安全监测委员会建议停止安慰剂组治疗时，获得了263名儿童（中位年龄24.7个月）的数据；132名（50%）服用异烟肼。中位随访时间为5.7（四分位间距2.0 - 9.7）个月。意向性分析显示，异烟肼组的死亡率低于安慰剂组（11例（8%）对21例（16%），风险比0.46，95%置信区间0.22至0.95，P = 0.015）。该益处适用于疾病控制中心的临床分类以及所有年龄段。每周三次或每日服用异烟肼的儿童死亡率降低情况相似。异烟肼组的结核病发病率低于安慰剂组（5例，3.8%）（13例，9.9%）（风险比0.28，0.10至0.78，P = 0.005）。所有经培养确诊的结核病病例均在安慰剂组儿童中。
异烟肼预防治疗对感染HIV的儿童有早期生存益处，并可降低结核病发病率。在结核病高流行地区，预防治疗可能是降低此类儿童死亡率的有效公共卫生干预措施。
临床试验NCT00330304。
