6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial
6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(11)60204-3
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发表时间：
2011-05-07
期刊：
影响因子：
168.9
通讯作者：
Wells, Charles D.
中科院分区：
文献类型：
--
作者：
Samandari, Taraz;Agizew, Tefera B.;Wells, Charles D.
背景根据WHO的指导方针，博茨瓦纳的HIV感染者每天接受异烟肼预防性治疗，而无需进行结核菌素皮肤试验，但预防性治疗的持续时间限制为6个月。我们的目的是评估延长异烟肼therapeutic.Methods的有效性，在我们的随机，双盲，安慰剂对照试验，我们招募了成年人感染艾滋病毒的年龄在18岁或以上的政府艾滋病毒护理诊所在博茨瓦纳。排除标准包括目前的疾病，如咳嗽和异常的胸部X线片，没有先前的结核病或肺炎。根据计算机生成的随机化列表，将符合条件的个体随机分配（1：1）接受6个月的开放标签异烟肼，然后接受30个月的盲态安慰剂（对照组）或6个月的开放标签异烟肼，然后接受30个月的盲态异烟肼（继续异烟肼组），每个诊所的随机化列表为10个排列区组。如果参与者的CD 4阳性淋巴细胞计数低于200个细胞/μ L，则提供抗逆转录病毒治疗。我们使用考克斯回归分析和对数秩检验来比较两组的结核病发病率。采用考克斯回归模型评估抗逆转录病毒治疗的效果。该试验在www.example.com上注册ClinicalTrials.gov，编号为NCT 00164281。对照组989例，结核病发病率3.4%，（2.0%）（每年发生率1.26% vs 0.72%;风险比0.57，95% CI 0.33-0.99，p=0.047）。接受安慰剂治疗的个体在完成开放标签异烟肼治疗后约200天结核病发病率升高。入选时结核菌素皮试阳性（即硬结>= 5 mm）的受试者从持续异烟肼治疗中获益显著（0.26，0.09-0.80，p=0.02），而结核菌素皮试阴性的受试者获益不显著（0.75，0.38-1.46，p=0.40）。在研究完成时，1995名参与者中有946名（47%）开始了抗逆转录病毒治疗。与未接受抗逆转录病毒治疗的参与者相比，接受360天抗逆转录病毒治疗的参与者结核病发病率降低了50%（调整后的风险比为0.50，95% CI为0.26-0.97）。对照组和继续服用异烟肼组的严重不良事件和死亡情况大致相同。解释在结核病流行的情况下，对于艾滋病毒感染者来说，36个月的异烟肼预防比6个月的预防更有效，并且主要受益于那些结核菌素皮肤试验阳性的人。
Background In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy.Methods In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per mu L. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281.Findings Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3.4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2.0%) in 1006 allocated to the continued isoniazid group (incidence 1.26% per year vs 0.72%; hazard ratio 0.57, 95% CI 0.33-0.99, p=0.047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, >= 5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0.26, 0.09-0.80, p=0.02), whereas participants who were tuberculin skin test-negative received no significant benefit (0 75, 0.38-1.46, p=0.40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0.50, 95% CI 0.26-0.97). Severe adverse events and death were much the same in the control and continued isoniazid groups.Interpretation In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive.