Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial.
Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial.
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DOI：
10.1016/s1473-3099(13)70692-3
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发表时间：
2014-04
影响因子：
56.3
通讯作者：
Cohen, Myron S.
中科院分区：
文献类型：
--
作者：
Grinsztejn, Beatriz;Hosseinipour, Mina C.;Ribaudo, Heather J.;Swindells, Susan;Eron, Joseph;Chen, Ying Q.;Wang, Lei;Ou, San-San;Anderson, Maija;McCauley, Marybeth;Gamble, Theresa;Kumarasamy, Nagalingeshwaran;Hakim, James G.;Kumwenda, Johnstone;Pilotto, Jose H. S.;Godbole, Sheela V.;Chariyalertsak, Suwat;de Melo, Marineide Goncalves;Mayer, Kenneth H.;Eshleman, Susan H.;Piwowar-Manning, Estelle;Makhema, Joseph;Mills, Lisa A.;Panchia, Ravindre;Sanne, Ian;Gallant, Joel;Hoffman, Irving;Taha, Taha E.;Nielsen-Saines, Karin;Celentano, David;Essex, Max;Havlir, Diane;Cohen, Myron S.
对艾滋病毒-1感染使用抗逆转录病毒治疗降低了与艾滋病有关的发病率和死亡率，并防止了艾滋病毒-1的性传播。然而，启动抗逆转录病毒治疗以减少艾滋病毒-1感染或非艾滋病临床事件的进展的最佳时间尚不清楚。我们之前曾报道，早期抗逆转录病毒治疗可以将HIV-1的传播减少96%。我们的目的是比较早期和延迟开始抗逆转录病毒治疗对临床结果的影响。HPTN 052试验是一项随机对照试验，在9个国家的13个地点进行。我们将HIV-1血清不一致的夫妇纳入研究，并通过按地点分层的排列区组随机将他们随机分配到早期或延迟的抗逆转录病毒治疗中。随机分配是非盲目的。每对夫妇中感染HIV-1的成员要么在进入研究时(早期治疗组)开始抗逆转录病毒治疗，要么在CD4计数下降或出现艾滋病相关疾病后开始抗逆转录病毒治疗(延迟治疗组)。主要事件是艾滋病临床事件(世界卫生组织第四阶段HIV-1疾病、结核病和严重细菌感染)和下列与艾滋病无关的严重疾病：严重心血管或血管疾病、严重肝病、终末期肾病、新发糖尿病和非艾滋病恶性疾病。按意向处理进行分析。这项试验在ClinicalTrials.gov注册，编号NCT00074581。1763名HIV-1感染者和一名血清不一致的伴侣参加了这项研究；886人被分配到早期抗逆转录病毒治疗，877人被推迟治疗(两名个人在随机分组后被排除在这一组之外)。随机分组后，早期治疗组患者的CD_4细胞数中位数为每μL 442个(IQR373-522)个细胞，而那些被分配延迟抗逆转录病毒治疗的患者的CD_4细胞数中位数为每μL 428个(357-522)个细胞。在延迟组，开始抗逆转录病毒治疗的CD_4细胞计数中位数为230个/μL(IQR197-249)，报告了57名早期开始治疗的患者与77名分配给延迟抗逆转录病毒治疗的患者的主要临床事件(风险比0·73，95%可信区间0·52-1·03；p=0.074)。被分配到早期抗逆转录病毒治疗的40名参与者中有40人记录了新发艾滋病事件，延迟治疗组有61人发生了新发艾滋病事件(0·，0·43-0·96；p=0.031)，17名患者和34名患者发生了结核病(0·49，0·28-0·89，p=0.018)，原发非艾滋病事件很少见(早期组12人，延迟治疗组9人)。总体而言，早期治疗组发生498例原发和继发结局(发生率24.9/100人年，95%可信区间22.5-27.5)，而延迟治疗组585例(29.2/100人年，26.5-32.1%；P=0.025)。26人死亡，11人被分配到早期抗逆转录病毒治疗，15人被分配到延迟治疗组。早期开始抗逆转录病毒治疗推迟了艾滋病事件的发生时间，并减少了原发和继发结果的发生率。记录的临床益处，再加上以前报告的艾滋病毒-1传播风险的显著降低，为更早开始抗逆转录病毒治疗提供了强有力的支持。美国国家过敏症和传染病研究所。
Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197–249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52–1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43–0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28–0·89, p=0·018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5–27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5–32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group. Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment. US National Institute of Allergy and Infectious Diseases.