CAUSALab and Department of Epidemiology, Harvard T H Chan School of Public Health, Harvard University, Boston, MA, USA.
CAUSALab and Department of Epidemiology, Harvard T H Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Lancet HIV. 2023 Nov;10(11):e723-e732. doi: 10.1016/S2352-3018(23)00233-3.
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.
最近的一项观察性研究表明，与接受其他抗逆转录病毒治疗方案（ART）的 HIV 初治患者相比，接受整合酶链转移抑制剂（INSTI）为基础的 ART 的 HIV 初治患者发生心血管事件的风险可能更高。我们旨在分别在 HIV 初治和 HIV 经治患者中模拟目标试验，以检查使用 INSTI 为基础的方案与其他 ART 方案对 4 年心血管事件风险的影响。
我们使用来自欧洲和北美的两个国际 HIV 队列联盟的 12 个队列的常规记录临床数据，这些数据来自欧洲和北美的 HIV 队列。对于从未接受过 ART（即 HIV 初治）的个体的目标试验，入选标准为年龄≥18 岁，在接受 ART 前可检测到 HIV-RNA（>50 拷贝/mL），且无心血管事件或癌症病史。对于之前使用过非 INSTI 为基础的 ART（即 HIV 经治）的个体的目标试验的入选标准相同，只是个体必须至少使用过一种非 INSTI 为基础的 ART 方案且病毒抑制（<50 拷贝/mL）。我们评估了从 2013 年 1 月至 2023 年 1 月每个个体月的两个试验的入选资格，并根据他们的数据为个体分配治疗策略。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标准化的 4 年心血管事件（心肌梗死、中风或有创性心血管手术）风险。在方案符合分析中，如果个体偏离其分配的治疗策略超过 2 个月，我们对个体进行了 censoring，并通过其随时间变化的未 censoring 概率的倒数对未 censored 个体进行加权。权重的分母通过包含基线和时间变化协变量的汇总逻辑模型进行估计。
在 HIV 初治个体中，包括了 10767 名 INSTI 起始者和 8292 名非 INSTI 起始者。INSTI 起始者中发生了 43 例心血管事件（中位随访 29 个月；IQR 15-45），非 INSTI 起始者中发生了 52 例（39 个月；18-47）：INSTI 起始者的标准化 4 年风险为 0.76%（95%CI 0.51-1.04），非 INSTI 起始者为 0.75%（0.54-0.98）；风险比 1.01（0.57-1.57）；风险差异 0.0089%（-0.43-0.36）。在 HIV 经治个体中，包括了 7875 名 INSTI 起始者和 373965 名非 INSTI 起始者。INSTI 起始者中发生了 56 例事件（中位随访 18 个月；IQR 9-29），非 INSTI 起始者中发生了 3103 例（808 例）（26 个月；15-37）：INSTI 起始者的标准化 4 年风险为 1.41%（95%CI 0.88-2.03），非 INSTI 起始者为 1.48%（1.28-1.71）；风险比 0.95（0.60-1.36）；风险差异 -0.068%（-0.60-0.52）。
我们估计，在 HIV 初治和 HIV 经治患者中，使用 INSTI 并不会导致心血管事件的临床意义上的增加。
美国国立过敏和传染病研究所和美国国家酒精滥用和酒精中毒研究所。
