Risk of clinical events in virologically suppressed people with HIV switching to a two-drug regimen vs. remaining on a three-drug regimen: a target trial emulation.
Cristina Mussini, Andrea Giacomelli, Eugenia Quiros-Roldan, Valentina Mazzotta, Antonio Di Biagio, Andrea De Vito, Andrea Costantini, Gabriella D'Ettorre, Andrea Giacometti, Alessandra Vergori, Alessandro Tavelli, Vincenzo Malagnino, Antonella Castagna, Johanna Chester, Andrea Antinori, Antonella d'Arminio Monforte, Alessandro Cozzi-Lepri
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引用次数: 0
Abstract
Background: Guidelines support the switch to a two-drug regimen (2DR) in virologically suppressed people with HIV (PWH) on a three-drug regimen (3DR). Randomized clinical trials have not included clinical outcomes in study endpoints. We provide estimates of 3-year clinical risk by means of a target trial emulation using the data of a large cohort of PWH in Italy.
Methods: PWH from the Icona Foundation Study who were virologically suppressed (HIV-RNA ≤50 copies/mL) for ≥6 months on a 3DR on or after November 2014, were enrolled (database closure on July 31, 2024). PWH were classified according to therapeutic strategies: switching to 2DR (protease inhibitors or dolutegravir plus lamivudine or dolutegravir plus rilpivirine) or remaining on 3DR (any combination). The primary endpoint was the time to the first clinical composite event (cardiovascular disease [CVD], cancer [AIDS and non-AIDS related], or death). We calculated the difference in 3-year risk between therapeutic strategies, estimated using a weighted non-parametric Kaplan-Meier estimator.
Findings: 7672 participants entered the analysis: 629 (8.2%) switching to 2DR and 7043 (91.8%) remaining on 3DR. Over the 3-year follow-up, 408 events were registered (64 CVD, 234 cancer, and 110 deaths). The 3-year adjusted risk estimate was 2.55 (95% CI 1.72, 5.33) in 2DR vs. 4.69 (95% CI 4.48, 6.17) in 3DR. The difference (-2.15% [95% CI -3.56%, -0.20%]) in favor of 2DR was mainly driven by events of non-AIDS related cancer and mortality.
Interpretation: This study provides evidence that virologically suppressed PWH can be safely switched to 2DR, and may slightly reduce the 3-year risk of a composite clinical outcome.
Funding: The Icona Foundation Study is supported by unrestricted grants from Gilead Sciences, ViiV Healthcare, Merck Sharpe & Dohme.
背景：指南支持在病毒学抑制的HIV感染者（PWH）中使用三药方案（3DR）切换到双药方案（2DR）。随机临床试验未将临床结果纳入研究终点。我们利用意大利一大批PWH患者的数据，通过目标试验模拟，提供了3年临床风险的估计。方法：纳入2014年11月或之后接受3DR治疗且病毒学抑制（HIV-RNA≤50拷贝/mL）≥6个月的来自Icona基金会研究的PWH（数据库于2024年7月31日关闭）。根据治疗策略对PWH进行分类：切换到2DR（蛋白酶抑制剂或多替格拉韦加拉米夫定或多替格拉韦加利匹韦林）或继续使用3DR（任何组合）。主要终点是发生第一次临床复合事件（心血管疾病[CVD]、癌症[艾滋病和非艾滋病相关]或死亡）的时间。我们计算了不同治疗策略的3年风险差异，使用加权非参数Kaplan-Meier估计器进行估计。结果：7672名参与者进入分析：629名（8.2%）转向2DR， 7043名（91.8%）继续使用3DR。在3年的随访中，记录了408例事件（64例心血管疾病，234例癌症，110例死亡）。2期患者3年调整后的风险估计值为2.55 (95% CI 1.72, 5.33)， 3期患者为4.69 （95% CI 4.48, 6.17）。支持2DR的差异（-2.15% [95% CI -3.56%, -0.20%]）主要是由非艾滋病相关癌症事件和死亡率驱动的。解释：该研究提供了病毒学抑制的PWH可以安全地转换为2DR的证据，并可能略微降低3年复合临床结果的风险。资助：Icona基金会研究由吉利德科学公司、ViiV医疗保健公司、默沙东公司提供无限制资助。
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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