Lundgren Jens D, Babiker Abdel G, Sharma Shweta, Grund Birgit, Phillips Andrew N, Matthews Gail, Kan Virginia L, Aagaard Bitten, Abo Inka, Alston Beverly, Arenas-Pinto Alejandro, Avihingsanon Anchalee, Badal-Faesen Sharlaa, Brites Carlos, Carey Cate, Casseb Jorge, Clarke Amanda, Collins Simon, Corbelli Giulio Maria, Dao Sounkalo, Denning Eileen T, Emery Sean, Eriobu Nnakelu, Florence Eric, Furrer Hansjakob, Fätkenheuer Gerd, Gerstoft Jan, Gisslén Magnus, Goodall Katharine, Henry Keith, Horban Andrzej, Hoy Jennifer, Hudson Fleur, Azwa Raja Iskandar Shah Raja, Kedem Eynat, Kelleher Anthony, Kityo Cissy, Klingman Karin, Rosa Alberto La, Leturque Nicolas, Lifson Alan R, Losso Marcelo, Lutaakome Joseph, Madero Juan Sierra, Mallon Patrick, Mansinho Kamal, Filali Kamal Marhoum El, Molina Jean-Michel, Murray Daniel D, Nagalingeswaran Kumarasamy, Nozza Silvia, Ormaasen Vidar, Paredes Roger, Peireira Luiz Carlos, Pillay Sandy, Polizzotto Mark N, Raben Dorthe, Rieger Armin, Sanchez Adriana, Schechter Mauro, Sedlacek Dalibor, Staub Therese, Touloumi Giota, Turner Melissa, Madruga Jose Valdez, Vjecha Michael, Wolff Marcelo, Wood Robin, Zilmer Kai, Lane H Clifford, Neaton James D
CHIP Centre of Excellence for Health, Immunity, and Infections, Department of Infectious Diseases, Rigshospitalet, Copenhagen.
Medical Research Council Clinical Trials Unit, University College London, London.
NEJM Evid. 2023 Mar;2(3). doi: 10.1056/evidoa2200302. Epub 2023 Feb 27.
For people with HIV and CD4 counts >500 cells/mm, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4 counts are <350 cells/mm. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.
The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4 counts .500 cells/mm to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.
Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4 count was 648 and 460 cells/mm in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4 difference was 199 cells/mm. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4 count difference was 155 cells/mm. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).
Among adults with CD4 counts >500 cells/mm, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
对于人类免疫缺陷病毒（HIV）感染者且CD4细胞计数>500个/mm³的人群，与推迟治疗直至CD4细胞计数<350个/mm³相比，早期启动抗逆转录病毒疗法（ART）可降低严重艾滋病和严重非艾滋病（SNA）风险。对于那些推迟治疗的人，一旦启动ART，艾滋病和SNA的额外风险是否持续存在尚不确定。
如先前报道，抗逆转录病毒治疗时机战略（START）试验将4684例未接受过ART的HIV阳性成年人随机分组，这些成年人的CD4细胞计数≥500个/mm³，随机分组后立即开始治疗（n = 2325）或推迟治疗（n = 2359）。2015年，报告了立即治疗组主要终点（艾滋病、SNA或死亡）风险降低57%，并为推迟治疗组提供了ART。本文报告了持续至2021年12月31日的随访情况。使用Cox比例风险模型比较从随机分组至2015年12月31日与2016年1月1日至2021年12月31日主要终点的风险比。
截至2015年12月31日，即上次报告截止日期约7个月后，立即治疗组和推迟治疗组在开始治疗时的CD4细胞计数中位数分别为648和460个/mm³。立即治疗组和推迟治疗组接受ART的随访时间百分比分别为95%和36%，平均CD4差异为199个/mm³。2016年1月1日之后，立即治疗组和推迟治疗组接受治疗的随访时间百分比分别为97.2%和94.1%，CD4细胞计数差异为155个/mm³。2016年1月1日之后，共有89例立即治疗组和113例推迟治疗组参与者出现主要终点（2016年前风险比为0.79[95%置信区间，0.60至1.04]，而风险比为0.47[95%置信区间，0.34至0.65；P<0.001]）（风险比差异P = 0.02）。
在CD4细胞计数>500个/mm³的成年人中，与推迟开始治疗相关的艾滋病和SNA额外风险在启动ART后有所降低，但仍存在持续的额外风险。（由美国国立过敏与传染病研究所等资助。）
