Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa - A novel randomized incremental recruitment study
Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa - A novel randomized incremental recruitment study
复制标题
DOI：
10.1001/jama.293.22.2719
复制
发表时间：
2005-06-08
影响因子：
120.7
通讯作者：
Churchyard, GJ
中科院分区：
文献类型：
--
作者：
Grant, AD;Charalambous, S;Churchyard, GJ
结核病预防治疗在临床试验中降低了人类免疫缺陷病毒（HIV）感染者的结核病发病率，但实施有限，没有常规条件下有效性的数据。目的了解门诊对成人hiv感染者常规使用异烟肼预防治疗对结核病发病率的影响。采用新型增量招募设计的随机干预研究。在1999年至2001年（抗逆转录病毒疗法可用之前），南非一家金矿公司的1655名感染艾滋病毒的男性雇员（年龄中位数为37岁）参加了这项研究。中位随访时间为22.1个月。干预措施按随机顺序邀请员工参加工作场所的艾滋病毒诊所。无活动性肺结核证据的参与者自行服用异烟肼300毫克/天，持续6个月。主要结局指标临床入组前后结核病发病率（包括首次发病和复发）。结果纳入分析的1655名男性中，有1016人至少去过一次诊所。702名男性中有679名（97%）符合开始异烟肼初级预防治疗的条件。临床入组前和入组后的结核病发病率分别为11.9 / 100人/年和9.0 / 100人/年（经日历期调整后的发病率比[IRR]为0.68；95%可信区间[CI]为0.48-0.96）。在调整日历期、年龄和矽肺分级的多变量分析中，临床入组的结核病IRR为0.62 （95% Cl, 0.43-0.89）。在进一步的分析中，排除有结核病史的个体（因此不适合异烟肼预防治疗），临床入组的调整IRR为0.54 （95% Cl, 0.35-0.83）。结论：在一家为hiv感染的成人提供初级异烟肼预防治疗的诊所入组，总体上降低了38%的结核病发病率，在研究之前没有结核病史的个体中降低了46%。尽管采取了异烟肼预防性治疗，但结核病的发病率仍然很高，需要进一步开展工作，以确定如何最有效地使用其他干预措施，降低艾滋病毒感染者因结核病引起的发病率和死亡率。
Context Tuberculosis preventive therapy reduces tuberculosis incidence among human immunodeficiency virus (HIV)-infected individuals in clinical trials, but implementation has been limited and there are no data on effectiveness under routine conditions.Objective To determine the effect on tuberculosis incidence of a clinic providing isoniazid preventive therapy to HIV-infected adults under routine conditions.,Design, Setting, and Participants Randomized intervention study with a novel incremental recruitment design. Between 1999 and 2001 (before antiretroviral therapy was available), 1655 HIV-infected male employees of a South African gold-mining company (median age, 37 years) were enrolled in the study. Median follow-up was 22.1 months.Intervention Employees were invited in random sequence to attend a workplace HIV clinic. Isoniazid, 300 mg/d, was self-administered for 6 months among attendees with no evidence of active tuberculosis.Main Outcome Measure Incidence of tuberculosis (including both first and recurrent episodes) during the periods before and after clinic enrollment.Results A total of 1016 of 1655 men included in the analysis attended the clinic at least once. Six hundred seventy-nine (97%) of 702 men eligible to start primary isoniazid preventive therapy did so. The tuberculosis incidence rate before vs after clinic enrollment was 11.9 vs 9.0 per 100 person-years, respectively (incidence rate ratio [IRR] after adjustment for calendar period, 0.68; 95% confidence interval [CI], 0.48-0.96). In a multivariable analysis adjusting for calendar period, age, and silicosis grade, the tuberculosis IRR for clinic enrollment was 0.62 (95% Cl, 0.43-0.89). In a further analysis excluding individuals with a history of tuberculosis (and, hence, ineligible for isoniazid preventive therapy), the adjusted IRR for clinic enrollment was 0.54 (95% Cl, 0.35-0.83).Conclusions Enrollment in a clinic offering primary isoniazid preventive therapy to HIV-infected adults reduced tuberculosis incidence by 38% overall and by 46% among individuals with no history of tuberculosis prior to the study. Tuberculosis incidence remained high despite isoniazid preventive therapy, and further work is needed to determine how to use additional interventions most effectively to reduce morbidity and mortality due to tuberculosis in HIV-infected persons.