Inserm 1219, University of Bordeaux, Bordeaux, France; Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire.
Inserm 1219, University of Bordeaux, Bordeaux, France; Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire.
Lancet Glob Health. 2017 Nov;5(11):e1080-e1089. doi: 10.1016/S2214-109X(17)30372-8.
Temprano ANRS 12136 was a factorial 2 × 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 Côte 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.
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 post-trial 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.
Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) 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=0·77) or between IPT and time (p=0·94) on mortality.
In Côte 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.
National Research Agency on AIDS and Viral Hepatitis (ANRS).
Temprano ANRS 12136 是一项两因素、两水平的临床试验，评估了早期抗逆转录病毒治疗（ART；即在未达到世界卫生组织（WHO）指南推荐开始 ART 的 CD4 细胞计数阈值的情况下进行的 ART，该指南是研究期间的标准）和 6 个月异烟肼预防性治疗（IPT）对感染 HIV 的成年人的益处。早期 ART 和 IPT 均独立降低了 30 个月时严重发病的风险。在此，我们报告了 Temprano 长期随访中 IPT 降低死亡率的疗效。
对于 Temprano，参与者被随机分配到四个组（延迟 ART、延迟 ART 加 IPT、早期 ART 或早期 ART 加 IPT）。完成试验随访的参与者被邀请参加试验后阶段。主要试验后阶段终点是死亡，分析时采用意向治疗原则。我们使用 Cox 比例模型比较了 Temprano 纳入至随访期末期间，IPT 和无 IPT 策略之间的全因死亡率。
2008 年 3 月 18 日至 2015 年 1 月 5 日，2056 名患者（平均基线 CD4 计数为每微升 477 个细胞）接受了 9404 患者年的随访（Temprano 为 4757 年；试验后阶段为 4647 年）。中位随访时间为 4.9 年（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 例随机分配 IPT（6 年概率为 4.1%，95%CI 2.9-5.7），52 例随机分配无 IPT（6.9%，5.1-9.2）。调整 ART 策略（早期 vs 延迟）后，接受 IPT 的患者死亡风险比未接受 IPT 的患者低 0.63（95%CI，0.41-0.97），调整 ART 策略、基线 CD4 细胞计数和其他关键特征后，风险比为 0.61（0.39-0.94）。IPT 与 ART（p=0.77）或 IPT 与时间（p=0.94）之间的死亡无统计学交互作用的证据。
在结核病发病率最后报告为每 10 万人 159 例的科特迪瓦，6 个月 IPT 可持久地降低 HIV 感染者的死亡率，即使在 CD4 细胞计数较高且已开始 ART 的人群中也是如此。
国家艾滋病和病毒性肝炎研究机构（ANRS）。
