Prognostic Value of Blood Epigenetic Biomarkers of Aging in Persons With Well-Controlled HIV-1 Infection
Year: 2025
Type: article
Abstract: BACKGROUND: Epigenetic age acceleration (EAA) predicts morbidity and mortality in the general population, but its prognostic utility in people with human immunodeficiency virus (HIV) (PWH) on suppressive antiretroviral therapy remains unclear. METHODS: Longitudinal observational cohort of 216 PWH with sustained virological suppression (median 6.5 years) recruited from the DUAL-GESIDA trial and La Paz Aging Cohort (Spain). Baseline blood DNA methylation was assessed to evaluate 8 epigenetic clocks, their principal-component (PC) derivatives, and the telomere length estimator. Over 10 years, we recorded AIDS, serious non-AIDS (SNAEs), and aging-related events. Associations between EAA and outcomes were evaluated by multivariate Cox models. RESULTS: One hundred five participants experienced ≥ 1 event, 162 events recorded in total (1 AIDS event, 65 SNAEs, and 96 aging-related events). A positive EAA by Horvath's clock was associated with a 50% higher risk of aging-related events. Participants with positive EAA according to PC-GrimAge, GrimAge V1-V2, as well as Hannum´s clock experienced more than 2-fold increased risk of SNAEs. Positive EAA by PC-GrimAge and PhenoAge was associated with an increased risk of non-AIDS cancer. Additionally, positive EAA according to GrimAge V1-V2 was linked to a 4-fold increase in all-cause mortality risk. All individuals who died (n = 17) had a baseline DunedinPACE value >1. No associations were found for the composite endpoint or cardiovascular events. CONCLUSIONS: In this preliminary study, GrimAge and PC-GrimAge were associated with increased risk of adverse outcomes in people with well-controlled HIV infection. These findings suggest their potential as long-term health-risk biomarkers, warranting validation in larger cohorts.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciaf537
Authors: Patricia Martínez-Martín, Andrés Esteban-Cantos, Francisco Jurado, Rocío Montejano, Lucía Gutiérrez-García, Alejandro de Gea Grela, Juan Carlos González, Cristina Marcelo, Alejandro Díez Vidal, María del Mar Arcos-Rueda, Rosa De Miguel Buckley, Jose I Bernardino, María Jiménez-González, María de Lagarde, José Sanz-Moreno, Pablo Ryan, Vicente Estrada Pérez, Leire Pérez-Latorre, Juan Emilio Losa-García, Berta Rodés, José R Arribas
Institutions: Hospital Universitario La Paz, Hospital La Paz Institute for Health Research, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Spanish National Cancer Research Centre, Centro de Investigación Biomédica en Red de Cáncer, Hospital Universitario 12 De Octubre, Hospital Universitario Príncipe de Asturias, Hospital Universitario Infanta Leonor, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital Universitario Fundación Alcorcón
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4414678579