Mussini Cristina, Giacomelli Andrea, Quiros-Roldan Eugenia, Mazzotta Valentina, Di Biagio Antonio, De Vito Andrea, Costantini Andrea, D'Ettorre Gabriella, Giacometti Andrea, Vergori Alessandra, Tavelli Alessandro, Malagnino Vincenzo, Castagna Antonella, Chester Johanna, Antinori Andrea, d'Arminio Monforte Antonella, Cozzi-Lepri Alessandro
Infectious Diseases Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena; University of Modena and Reggio Emilia, School of Medicine, Modena, Italy.
Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, III Infectious Disease Unit, ASST-Fatebenefratelli Sacco Milano, Italy.
EClinicalMedicine. 2025 Jul 24;86:103368. doi: 10.1016/j.eclinm.2025.103368. eCollection 2025 Aug.
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.
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.
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.
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.
The Icona Foundation Study is supported by unrestricted grants from Gilead Sciences, ViiV Healthcare, Merck Sharpe & Dohme.
指南支持病毒学抑制的接受三联药物治疗方案（3DR）的HIV感染者（PWH）换用两联药物治疗方案（2DR）。随机临床试验未将临床结局纳入研究终点。我们利用意大利一大群PWH的数据，通过目标试验模拟来估计3年临床风险。
纳入2014年11月1日或之后接受3DR且病毒学抑制（HIV-RNA≤50拷贝/毫升）≥6个月的伊科纳基金会研究中的PWH（数据库于2024年7月31日关闭）。PWH根据治疗策略分类：换用2DR（蛋白酶抑制剂或多替拉韦加拉米夫定或多替拉韦加rilpivirine）或继续接受3DR（任何组合）。主要终点是首次发生临床复合事件（心血管疾病[CVD]、癌症[艾滋病相关和非艾滋病相关]或死亡）的时间。我们计算了治疗策略之间3年风险的差异，使用加权非参数Kaplan-Meier估计器进行估计。
7672名参与者进入分析：629名（8.2%）换用2DR，7043名（91.8%）继续接受3DR。在3年随访期间，记录了408起事件（64起CVD、234起癌症和110起死亡）。2DR组的3年调整风险估计值为2.55（95%CI 1.72，5.33），3DR组为4.69（95%CI 4.48，6.17）。有利于2DR的差异（-2.15%[95%CI -3.56%，-0.20%]）主要由非艾滋病相关癌症和死亡事件驱动。
本研究提供了证据，表明病毒学抑制的PWH可以安全地换用2DR，并且可能略微降低3年复合临床结局的风险。
伊科纳基金会研究由吉利德科学公司、维泰凯医药公司、默克夏普&多美公司的无限制赠款资助。
