Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial
Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial
复制标题
DOI：
10.1016/s2214-109x(17)30372-8
复制
发表时间：
2017-11-01
影响因子：
34.3
通讯作者：
Anglaret, Xavier
中科院分区：
文献类型：
--
作者：
Badje, Anani;Moh, Raoul;Anglaret, Xavier
Temprano ANRS 12136是一项2 × 2因子试验，评估了科特迪瓦艾滋病毒感染成人早期抗逆转录病毒治疗（ART，即未达到CD4细胞计数阈值的患者，用于推荐开始抗逆转录病毒治疗，根据世卫组织指南，这是研究期间的标准）和6个月异烟肼预防治疗（IPT）的益处。早期抗逆转录病毒治疗和IPT被证明可以独立地降低30个月时严重发病率的风险。在这里，我们介绍了IPT在降低坦普拉诺长期随访死亡率方面的疗效。对于Temprano，参与者随机分为四组（延迟ART、延迟ART + IPT、早期ART或早期ART + IPT）。完成试验随访的参与者被邀请参加试验后阶段。根据意向治疗原则分析，试验后阶段的主要终点是死亡。我们使用Cox比例模型来比较从坦普拉诺纳入到随访期结束时，IPT和无IPT策略之间的全因死亡率。在2008年3月18日至2015年1月5日期间，2056名患者（平均基线CD4计数477细胞/ μ L）随访了9404患者年（Temprano 4757；试验后期4647）。中位随访时间为4。9岁（IQR 3.3-5.8）。记录了86例死亡（Temprano 47例死亡，试验后阶段39例死亡），其中34例为随机分配IPT的患者（6年概率为4.1%,95% CI 2.9-5.7）， 52例为随机未分配IPT的患者（6.9%,5.1-9.2）。接受IPT的患者与未接受IPT的患者相比，在调整ART策略（早期vs延迟）后的死亡风险比为0.63 (95% CI, 0.41 - 0.97)，在调整ART策略、基线CD4细胞计数和其他关键特征后的死亡风险比为0.61（0.39-0.94）。IPT和ART之间没有统计学上的相互作用（p（相互作用）= 0）。77)或IPT与时间之间（p（交互作用）= 0.94）对死亡率的影响。在科特迪瓦，上一次报告的结核病发病率为每10万人中有159人，6个月的IPT对降低艾滋病毒感染者的死亡率具有持久的保护作用，即使对CD4细胞计数高和已开始抗逆转录病毒治疗的人也是如此。版权(C)作者(s)。Elsevier Ltd.出版。
Background Temprano ANRS 12136 was a factorial 2 x 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Cote d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano.Methods For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a posttrial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period.Findings Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per mu L) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4 . 9 years (IQR 3.3-5.8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4.1%, 95% CI 2.9-5.7) and 52 were in those randomly assigned no IPT (6.9%, 5.1-9.2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0.63 (95% CI, 0.41 to 0.97) after adjusting for the ART strategy (early vs deferred), and 0.61 (0.39-0.94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (p(interaction) = 0 .77) or between IPT and time (p(interaction) = 0.94) on mortality.Interpretation In Cote d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. Copyright (C) The Author(s). Published by Elsevier Ltd.