最近的一项观察性研究表明，与接受其他 ART 方案的患者相比，接受基于整合酶链转移抑制剂 (INSTI) 的 ART 的未接受过抗逆转录病毒治疗 (ART) 的 HIV 感染者发生心血管事件的风险可能更高。我们的目的是分别在未接受过 ART 和经历过 ART 的 HIV 感染者中模拟目标试验，以检查使用基于 INSTI 的方案与其他 ART 方案相比对 4 年心血管事件风险的影响。我们使用了来自 12 名患者的常规记录临床数据。该队列从欧洲和北美的两个国际艾滋病毒感染者队列中收集了有关心血管事件、体重指数和血压的信息。对于以前从未使用过 ART（即未接受过 ART）的个体进行的目标试验，资格标准为年龄 18 岁或以上、未接受过 ART 时可检测到 HIV-RNA 测量（> 50 个拷贝/毫升），并且没有病史心血管事件或癌症。对于既往使用过基于非 INSTI 的 ART 的患者（即有过 ART 经验的患者），目标试验的资格标准是相同的，只是个体必须接受过至少一种非基于 INSTI 的 ART 方案并进行病毒抑制（每毫升≤50 个拷贝）。我们评估了 2013 年 1 月至 2023 年 1 月期间每个人月参加两项试验的资格，并为个体分配与其数据相符的治疗策略。我们通过调整时间和基线协变量的汇总逻辑回归模型估计了心血管事件（心肌梗死、中风或侵入性心血管手术）的标准化 4 年风险。在按方案分析中，如果个体偏离指定治疗策略超过 2 个月，我们会对个体进行审查，并根据其保持未经审查的时变概率的倒数对未经审查的个体进行加权。权重的分母是通过包含基线和时变协变量的合并逻辑模型估计的。对未接受 ART 的个体进行的分析包括 10 767 INSTI 发起者和 8292 INSTI 非发起者。 INSTI 发起者中有 43 起心血管事件（中位随访 29 个月；IQR 15-45），非发起者中有 52 起（39 个月；18-47）：标准化 4 年风险为 0·76% (95%) INSTI 引发剂中 CI 0·51 至 1·04)，非 INSTI 引发剂中 CI 0·75%（0·54 至 0·98）；风险比1·01（0·57至1·57）；风险差异 0·0089%（-0·43 至 0·36）。对有 ART 经验的个体进行的分析包括 7875 名 INSTI 发起者和 373 965 名非发起者。 INSTI 发起者中有 56 起事件（中位随访 18 个月；IQR 9-29），非 INSTI 发起者中有 3103 起事件（808 个独特）（26 个月；15-37）：标准化 4 年风险INSTI 引发剂中为 1·41%（95% CI 0·88 至 2·03），非引发剂中为 1·48%（1·28 至 1·71）；风险比0·95（0·60至1·36）；风险差异 -0·068%（-0·60 至 0·52）。我们估计，对于未接受过 ART 治疗和经历过 ART 治疗的 HIV 感染者，使用 INSTI 不会导致具有临床意义的心血管事件增加。和传染病以及国家酒精滥用和酒精中毒研究所。版权所有 © 2023 Elsevier Ltd。保留所有权利。

A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events.We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates.The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52).We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV.National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.Copyright © 2023 Elsevier Ltd. All rights reserved.