Pneumology Unit, Internal Medicine Department, Bicêtre Hospital, Assistance Publique–Hôpitaux de Paris, Le Kremlin-Bicêtre, France.
N Engl J Med. 2011 Oct 20;365(16):1471-81. doi: 10.1056/NEJMoa1013911.
Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival.
A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients.
Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.).
结核病仍然是感染人类免疫缺陷病毒（HIV）的患者死亡的一个重要原因。在开始抗结核治疗时开始抗逆转录病毒治疗（ART）的时间与相关的稳健数据缺乏。
我们检验了这样一个假设，即 ART 的开始时间将显著影响新诊断为结核病且 CD4+T 细胞计数低于 200 个/立方毫米的未接受过抗逆转录病毒药物治疗的成年人的死亡率。在开始标准的 6 个月结核病治疗后，患者被随机分配到早期治疗（开始结核病治疗后 2 周）或晚期治疗（开始后 8 周）用司他夫定、拉米夫定和依非韦伦。主要终点是存活。
共有 661 名患者入组，中位随访时间为 25 个月。中位 CD4+T 细胞计数为 25 个/立方毫米，中位病毒载量为 5.64 log（10）拷贝/毫升。在接受早期 ART 的组中，死亡风险显著降低，332 名患者中有 59 例死亡（18%），而晚期 ART 组中 329 例患者中有 90 例死亡（27%）（风险比，0.62；95%置信区间[CI]；0.44 至 0.86；P=0.006）。早期 ART 组发生结核相关免疫重建炎症综合征的风险显著增加（风险比，2.51；95%CI，1.78 至 3.59；P<0.001）。无论研究组如何，CD4+T 细胞计数的中位数增加了 114 个/立方毫米，96.5%的患者在第 50 周时病毒载量无法检测到。
在 CD4+T 细胞计数为 200 个/立方毫米或更低的 HIV 感染成年人中，在开始结核病治疗后 2 周开始 ART 可显著提高生存率。（由法国国家艾滋病和病毒性肝炎研究机构和美国国立卫生研究院资助；CAMELIA ClinicalTrials.gov 编号，NCT01300481。）
