复方新诺明预防用药在降低接受抗结核治疗的HIV感染成人死亡率中的作用：随机临床试验
Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial.
作者信息
Nunn Andrew J, Mwaba Peter, Chintu Chifumbe, Mwinga Alwyn, Darbyshire Janet H, Zumla Alimuddin
机构信息
Medical Research Council Clinical Trials Unit, London NW1 2DA.
出版信息
BMJ. 2008 Jul 10;337:a257. doi: 10.1136/bmj.a257.
OBJECTIVE
To assess the impact of prophylactic oral co-trimoxazole in reducing mortality in HIV positive Zambian adults being treated for pulmonary tuberculosis.
DESIGN
Double blind placebo controlled randomised clinical trial.
PARTICIPANTS
Two groups of antiretroviral treatment naive adults with HIV infection: patients newly diagnosed as having tuberculosis and receiving tuberculosis treatment either for the first time or for retreatment after relapse; previously treated patients not receiving treatment.
INTERVENTION
Oral co-trimoxazole or matching placebo daily. Primary outcome measures Time to death and occurrence of serious adverse events related to study drug.
RESULTS
1003 patients were randomised: 835 (416 co-trimoxazole, 419 placebo) were receiving treatment for tuberculosis, 762 (376 co-trimoxazole, 386 placebo) of them newly diagnosed previously untreated patients and 73 (40 co-trimoxazole, 33 placebo) receiving a retreatment regimen; 168 (84 co-trimoxazole, 84 placebo) were not on treatment but had received treatment in the past. Of 835 participants receiving tuberculosis treatment, follow-up information was available for 757, with a total of 1012.6 person years of follow-up. A total of 310 (147 co-trimoxazole, 163 placebo) participants died, corresponding to death rates of 27.3 and 34.4 per 100 person years. In the Cox regression analysis, the hazard ratio for death (co-trimoxazole:placebo) was 0.79 (95% confidence interval 0.63 to 0.99). The effect of co-trimoxazole waned with time, possibly owing to falling adherence levels; in a per protocol analysis based on patients who spent at least 90% of their time at risk supplied with study drug, the hazard ratio was 0.65 (0.45 to 0.93).
CONCLUSIONS
Prophylaxis with co-trimoxazole reduces mortality in HIV infected adults with pulmonary tuberculosis. Co-trimoxazole was generally safe and well tolerated.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN15281875.
目的
评估预防性口服复方新诺明对降低接受肺结核治疗的赞比亚HIV阳性成年人死亡率的影响。
设计
双盲安慰剂对照随机临床试验。
参与者
两组未接受过抗逆转录病毒治疗的HIV感染成年人：新诊断为患有结核病且首次接受结核病治疗或复发后再次治疗的患者；既往接受过治疗但未接受治疗的患者。
干预措施
每日口服复方新诺明或匹配的安慰剂。主要结局指标：死亡时间和与研究药物相关的严重不良事件的发生情况。
结果
1003名患者被随机分组：835名（416名复方新诺明组，419名安慰剂组）正在接受结核病治疗，其中762名（376名复方新诺明组，386名安慰剂组）为新诊断的既往未治疗患者，73名（40名复方新诺明组，33名安慰剂组）接受再治疗方案；168名（84名复方新诺明组，84名安慰剂组）未接受治疗但过去接受过治疗。在835名接受结核病治疗的参与者中，有757名获得了随访信息，总计随访1012.6人年。共有310名（147名复方新诺明组，163名安慰剂组）参与者死亡，对应死亡率分别为每100人年27.3例和34.4例。在Cox回归分析中，死亡风险比（复方新诺明组：安慰剂组）为0.79（95%置信区间0.63至0.99）。复方新诺明的效果随时间减弱，可能是由于依从性下降；在基于至少90%的风险时间内服用研究药物的患者的符合方案分析中，风险比为0.65（0.45至0.93）。
结论
复方新诺明预防性用药可降低HIV感染的肺结核成年患者的死亡率。复方新诺明总体安全且耐受性良好。
试验注册号
Current Controlled Trials ISRCTN15281875 。
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