Effect of Pitavastatin on Epigenetic Aging Biomarkers in People With HIV: Pilot Substudy of the REPRIEVE Trial

作者：Michael J. Corley, Maya Watanabe, Alina P.S. Pang, Varun B. Dwaraka, Ryan Smith, Wadzanai Samaneka, Sarah Henn, Sonal S. Munsiff, María Saumoy, Sara McCallum, Kathleen V. Fitch, Sarah M Chu, Marissa R Diggs, Judith A. Aberg, Carlos Malvestutto, Carl J. Fichtenbaum, Judith S. Currier, Markella V. Zanni, Pamela S. Douglas, Michael T. Lu, Alan Landay, Kristine M. Erlandson, Heather J. Ribaudo, Steven Grinspoon · 发表于：Clinical Infectious Diseases · 年份：2025 · DOI：10.1093/cid/ciaf247 · 被引用次数：8 · 研究领域：HIV-related health complications and treatments、Epigenetics and DNA Methylation、HIV/AIDS drug development and treatment

BACKGROUND: People with human immunodeficiency virus (HIV, PWH) exhibit increased cardiovascular disease (CVD) risk and accelerated biological aging. REPRIEVE demonstrated that pitavastatin reduced major adverse cardiovascular events (MACE) in antiretroviral therapy (ART)-treated PWH with low-to-moderate traditional cardiovascular risk. It remains unknown whether statin therapy can modulate epigenetic aging in PWH. METHODS: We assessed epigenetic aging biomarkers using DNA methylation profiles from peripheral blood mononuclear cells (PBMCs) in a subset of 99 randomly selected US REPRIEVE participants (65 pitavastatin, 34 placebo) at baseline and 24 months. The primary outcomes were changes in second- and third-generation epigenetic clocks PCGrimAge (trained on mortality risk) and DunedinPACE (trained on rate of age-related multi-organ decline). RESULTS: Median chronological age was 57.0 (Q1, Q3: 56, 58) years and 100% of participants demonstrated epigenetic age acceleration, measured by the difference in PCGrimAge and chronological age (median difference 7.08 years [Q1, Q3: 4.69, 9.64]) at entry. Over 24 months, PCGrimAge remained accelerated with no significant differences between treatment arms (P = .89). However, the median pace of aging by the DunedinPACE increased in the placebo arm (0.036, Q1, Q3 [-0.018, 0.10], P = .021) but not in the pitavastatin arm (0.001, Q1, Q3 [-0.031, 0.036], [P = .77]), treatment group difference (P = .049). CONCLUSIONS: In this pilot study of...