Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.
Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.
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DOI：
10.1056/nejmoa1506816
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发表时间：
2015-08-27
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影响因子：
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通讯作者：
Neaton JD
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作者：
INSIGHT START Study Group;Lundgren JD;Babiker AG;Gordin F;Emery S;Grund B;Sharma S;Avihingsanon A;Cooper DA;Fätkenheuer G;Llibre JM;Molina JM;Munderi P;Schechter M;Wood R;Klingman KL;Collins S;Lane HC;Phillips AN;Neaton JD
来自随机试验的数据缺乏对无症状人类免疫缺陷病毒（HIV）感染患者开始抗逆转录病毒治疗的益处和风险，这些患者的CD 4+细胞计数超过350个/立方毫米。我们将CD 4+细胞计数超过每立方毫米500个的HIV阳性成年人随机分配为立即开始抗逆转录病毒治疗（立即启动组）或推迟治疗，直到CD 4+细胞计数降至每立方毫米350个细胞，或直到出现获得性免疫缺陷综合征（AIDS）或其他需要使用抗逆转录病毒治疗的疾病（推迟启动组）。主要复合终点是任何严重的艾滋病相关事件，严重的非艾滋病相关事件，或任何原因的死亡。共对4685例患者进行了平均3.0年的随访。在研究开始时，HIV病毒载量的中位数为每毫升12，759个拷贝，CD 4+计数的中位数为每立方毫米651个细胞。2015年5月15日，在中期分析的基础上，数据和安全监测委员会确定研究问题已经得到回答，并建议为延迟启动组的患者提供抗逆转录病毒治疗。主要终点发生在立即启动组的42例患者中（1.8%; 0.60例事件/100人年），而延迟启动组的96例患者中（4.1%; 1.38例事件/100人年），风险比为0.43（95%置信区间[CI]，0.30 - 0.62; P<0.001）。严重艾滋病相关和严重非艾滋病相关事件的风险比分别为0.28（95%CI，0.15 - 0.50; P<0.001）和0.61（95%CI，0.38 - 0.97; P = 0.04）。超过三分之二（68%）的主要终点发生在CD 4+细胞计数超过500个细胞/立方毫米的患者中。两组发生4级事件的风险相似，计划外住院的风险也相似。在CD 4+细胞计数超过每立方毫米500个细胞的HIV阳性成人中开始抗逆转录病毒治疗，比在CD 4+细胞计数下降到每立方毫米350个细胞后开始这种治疗的患者提供了净效益。（由国家过敏和传染病研究所等资助; START ClinicalTrials.gov编号，NCT 00867048。
Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause. A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P = 0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)