A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa
A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa
复制标题
DOI：
10.1056/nejmoa1507198
复制
发表时间：
2015-08-27
影响因子：
158.5
通讯作者：
Anglaret, Xavier
中科院分区：
文献类型：
--
作者：
Danel, Christine;Moh, Raoul;Anglaret, Xavier
在撒哈拉以南非洲，与人类免疫缺陷病毒（艾滋病毒）有关的结核病负担很重。我们进行了一项2 × 2析因设计的试验，以评估早期抗逆转录病毒治疗（ART）、6个月异烟肼预防性治疗（IPT）方法我们纳入了HIV 1型感染和CD 4 + T细胞亚群的受试者，根据世界卫生组织（WHO）的指南，每立方毫米细胞计数低于800个，并且不符合开始抗逆转录病毒治疗的标准。参与者被随机分配到四个治疗组之一：延迟ART（根据WHO标准开始ART），延迟ART加IPT，早期ART（立即开始ART）或早期ART加IPT。主要终点是病例定义中包含的疾病的复合终点，包括获得性免疫缺陷综合征（AIDS）、非AIDS定义的癌症、非AIDS定义的侵袭性细菌性疾病或30个月时任何原因导致的死亡。我们使用考克斯比例模型比较延迟ART和早期ART策略以及IPT和无IPT策略的结果。共观察到204例主要终点事件（3.8例事件/100人-年; 95%置信区间[CI]，3.3 - 4.4），包括68例基线CD 4+细胞计数至少为500个细胞/立方毫米的患者（3.2例事件/100人-年; 95% CI，2.4 - 4.0）。结核病和侵袭性细菌性疾病分别占主要终点事件的42%和27%。早期抗逆转录病毒治疗的死亡或严重艾滋病毒相关疾病的风险低于延迟治疗（校正后的风险比，0.56; 95% CI，0.41至0.76;基线CD 4+细胞计数>= 500个细胞/立方毫米的患者中校正后的风险比，0.56; 95% CI，0.33 - 0.94），且IPT组低于非IPT组（校正后的风险比，0.65; 95% CI，0.48至0.88;基线CD 4+细胞计数≥ 500个细胞/立方毫米的患者校正后的风险比，0.61; 95% CI，0.36至1.01）。30个月的3级或4级不良事件的概率没有显着不同的strategies.CONCLUSIONsIn this African country，立即ART和6个月的IPT独立导致严重疾病的发生率低于延迟ART和没有IPT，无论是总体还是在CD 4+细胞计数至少为500个细胞每立方毫米的患者中。
BACKGROUNDIn sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast.METHODSWe included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies.RESULTSA total of 2056 patients (41% with a baseline CD4+ count of >= 500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of >= 500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of >= 500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies.CONCLUSIONSIn this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter.