Timing of initiation of antiretroviral drugs during tuberculosis therapy.
Timing of initiation of antiretroviral drugs during tuberculosis therapy.
复制标题
DOI：
10.1056/nejmoa0905848
复制
发表时间：
2010-02-25
期刊：
影响因子：
--
通讯作者：
Abdool Karim Q
中科院分区：
文献类型：
--
作者：
Abdool Karim SS;Naidoo K;Grobler A;Padayatchi N;Baxter C;Gray A;Gengiah T;Nair G;Bamber S;Singh A;Khan M;Pienaar J;El-Sadr W;Friedland G;Abdool Karim Q
尽管合并HIV感染的结核病患者死亡率很高，但对于何时开始对这些患者进行抗逆转录病毒治疗(ART)，仍存在争议。我们在南非德班进行了一项开放标签的随机对照试验，以确定与结核病治疗相关的最佳ART启动时间。抗酸杆菌(AFB)涂片阳性合并HIV感染和CD4+细胞数为500个/mm~3的结核病患者(n=642)被随机分配到两个综合治疗组中的一个(在结核病治疗期间开始进行ART)或连续治疗组(在结核病治疗完成后开始进行ART)。参与者接受标准的结核病治疗、复方新诺明预防和每日一次的地丹诺辛、拉米夫定和依法韦仑ART方案。主要终点是全因死亡率。这项分析比较了序贯治疗臂和联合综合治疗臂截至2008年9月1日的数据，当时安全监测委员会建议停止序贯治疗臂。在研究组中，基线时的人口统计学、临床和实验室特征以及随访期间的不良事件发生率相似。综合治疗组死亡率比序贯治疗组低56%(风险比：0.44；95%可信区间：21%至75%；p=0.003)，综合治疗组死亡率为5.4‰(25例死亡；n=429)，序贯治疗组死亡率为12.1‰(27例死亡；n=213)。无论CD4+计数水平如何，死亡率都较低。在AFB阳性合并感染HIV和CD4+细胞数为500个/mm3的患者的结核病治疗期间启动抗逆转录病毒疗法，大大提高了存活率，并进一步推动了结核病和艾滋病服务的整合。
Despite high mortality rates in tuberculosis patients with HIV co-infection, there is continued controversy on when to initiate antiretroviral therapy (ART) in these patients. We conducted an open-label randomized controlled trial in Durban, South Africa to determine optimal timing of ART initiation in relation to TB treatment. Acid-fast bacilli (AFB) smear positive tuberculosis patients with HIV infection and CD4+ counts <500 cells/mm3 (n=642) were randomized to one of two integrated treatment arms (ART initiation during tuberculosis treatment) or to a sequential treatment arm (ART initiation upon tuberculosis treatment completion). Participants received standard tuberculosis therapy, cotrimoxazole prophylaxis and once daily didanosine, lamivudine and efavirenz ART regimen. The primary endpoint was all-cause mortality. This analysis compares data from the sequential treatment arm and the combined integrated treatment arms up to 1 September 2008, when the Safety Monitoring Committee recommended halting the sequential treatment arm. Demographic, clinical and laboratory characteristics at baseline and adverse event rates during follow-up were similar in the study arms. Mortality was 56% lower (hazard ratio: 0.44; 95% Confidence Interval: 21% to 75%; p = 0.003) in the integrated arm (5.4 per 100 person-years (25 deaths; n=429)) compared to sequential arm (12.1 per 100 person-years (27 deaths; n=213)). Mortality rates were lower regardless of CD4+ count level. Initiating ART during tuberculosis treatment in AFB positive patients with HIV co-infection and CD4+ counts <500 cells/mm3 significantly improves survival and provides further impetus for the integration of tuberculosis and AIDS services.