Cardiovascular Hazards of Abacavir- Versus Tenofovir-Containing Antiretroviral Therapies: Insights From an Analysis of the REPRIEVE Trial Cohort.

IF 3.8 4区医学 Q2 IMMUNOLOGY

Open Forum Infectious Diseases Pub Date : 2025-03-21 eCollection Date: 2025-04-01 DOI:10.1093/ofid/ofaf177

Emma Davies Smith, Carlos Malvestutto, Heather J Ribaudo, Carl J Fichtenbaum, Judith A Aberg, Maya Watanabe, Gerald S Bloomfield, Judith S Currier, Sarah M Chu, Kathleen V Fitch, Marissa R Diggs, Roger Bedimo, Javier Valencia, Cristina Gomez-Ayerbe, Indira Brar, Jose Valdez Madruga, Michael T Lu, Pamela S Douglas, Markella V Zanni, Steven K Grinspoon

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引用次数: 0

Abstract

Background: Prior analyses suggest that the nucleoside reverse transcriptase inhibitor (NRTI) abacavir (ABC), but not tenofovir (TFV), is associated with a 2-fold increase in the hazard of myocardial infarction. the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is ideally suited to evaluate the role of ABC and the TFV backbones, tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), in major adverse cardiovascular events (MACE).

Methods: We compared hazard of first MACE among people living with human immunodeficiency virus (HIV) at low-to-moderate cardiovascular risk using ABC (n = 883), TAF (n = 957), and TDF (n = 4274) at entry. Overlap weights balanced biasing factors, including age, sex at birth, atherosclerotic cardiovascular disease risk, CD4 count, estimated glomerular filtration rate, and anchor antiretroviral therapy. Associations between entry NRTI and MACEs were estimated using a marginal Cox proportional hazards model. Change of NRTI, or "switching," was common during follow-up. Additional associations were estimated by further censoring at first switch and applying time-updated inverse probability of censoring weighting (IPCW).

Results: Baseline-adjusted associations suggest clinically relevant increases in hazard of first MACE for ABC versus TAF (hazard ratio [HR], 1.5 [95% confidence interval {CI}, .9-2.3]) and ABC versus TDF (HR, 1.4 [95% CI, .9-2.1]), but not TAF versus TDF (HR, 0.9 [95% CI, .6-1.5]). With censoring at switch, HRs increased to 1.6 (95% CI, .9-2.7) for ABC versus TAF, 2.0 (95% CI, 1.2-3.4) for ABC versus TDF, and 1.2 (95% CI, .7-2.2) for TAF versus TDF. The largest HR observed was for ABC versus TDF and myocardial infarction (IPCW HR, 3.5 [95% CI, 1.3-9.4]).

Conclusions: Antiretroviral therapies with ABC backbones are associated with an increase in MACE compared to TFV backbones among people living with HIV at low-to-moderate cardiovascular risk.

Clinical trials registration: NCT02344290.

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阿巴卡韦与替诺福韦抗逆转录病毒治疗的心血管危害：来自REPRIEVE试验队列分析的见解

背景：先前的分析表明，核苷类逆转录酶抑制剂（NRTI）阿巴卡韦（ABC）与心肌梗死风险增加2倍相关，而不是替诺福韦（TFV）。预防HIV血管事件的随机试验（REPRIEVE）非常适合评估ABC和TFV主干，替诺福韦阿拉那胺（TAF）和富马酸替诺福韦二氧吡酯（TDF）在主要不良心血管事件（MACE）中的作用。方法：我们采用ABC （n = 883）、TAF （n = 957）和TDF （n = 4274）比较了低至中度心血管风险的人类免疫缺陷病毒（HIV）感染者首次MACE的风险。重叠权重平衡了偏倚因素，包括年龄、出生性别、动脉粥样硬化性心血管疾病风险、CD4计数、估计肾小球滤过率和锚定抗逆转录病毒治疗。使用边际Cox比例风险模型估计入组NRTI和mace之间的关联。NRTI的改变或“转换”在随访期间很常见。通过在第一次切换时进一步审查和应用时间更新的审查加权逆概率（IPCW）来估计其他关联。结果：经基线调整的相关性表明，ABC与TAF相比首次MACE的临床相关风险增加（风险比[HR]， 1.5[95%可信区间{CI}， 0.9 -2.3]）， ABC与TDF (HR, 1.4 [95% CI, 0.9 -2.1])，但TAF与TDF没有增加（HR, 0.9 [95% CI, 0.6 -1.5]）。在切换时进行筛选，ABC与TAF的hr增加到1.6 (95% CI, 0.9 -2.7)， ABC与TDF的hr增加到2.0 (95% CI, 1.2-3.4)， TAF与TDF的hr增加到1.2 （95% CI, 0.7 -2.2）。ABC与TDF和心肌梗死的HR最大（IPCW HR, 3.5 [95% CI, 1.3-9.4]）。结论：在低至中度心血管风险的HIV感染者中，与TFV主干相比，抗逆转录病毒治疗与ABC主干的MACE增加有关。临床试验注册：NCT02344290。

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来源期刊

Open Forum Infectious Diseases Medicine-Neurology (clinical)

CiteScore

6.70

自引率

4.80%

发文量

630

审稿时长

9 weeks

期刊介绍： Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.