Longitudinal Changes in Epigenetic Age Acceleration in Aviremic Human Immunodeficiency Virus–Infected Recipients of Long-term Antiretroviral Treatment
Andrés Esteban-Cantos, Rocío Montejano, Javier Rodríguez-Centeno, Gabriel Saiz-Medrano, Rosa de Miguel Buckley, Pilar Barrúz, José Ignacio Bernardino, Beatriz Mena-Garay, Julen Cadiñanos, María Jiménez-González, Julián Nevado, Eulalia Valencia, Mario Mayoral-Muñoz, José Ramón Arribas, Berta Rodés
Abstract
BACKGROUND: Human immunodeficiency virus (HIV) infection induces epigenetic age acceleration (EAA), but it remains unclear whether epigenetic aging continues to accelerate during successful antiretroviral therapy (ART) and prolonged virological suppression. METHODS: We longitudinally analyzed 63 long-term aviremic HIV-infected adults. Using blood DNA methylation patterns, we calculated EAA measures based on 3 epigenetic clocks (Horvath's clock, PhenoAge, and GrimAge). We recorded the emergence of serious AIDS-related and non-AIDS-related events throughout the study to assess its association with EAA. RESULTS: All participants were on stable ART and were virologically suppressed. After 4 years of follow-up, PhenoAge-EAA and GrimAge-EAA showed no differences, whereas Horvath-EAA slightly decreased (median difference, -0.53 years; P = .015). Longitudinal changes in EAA measures were independent of changes in CD4 cell counts, the ART regimen, or other HIV-related factors. Nineteen percent of participants experienced a serious clinical event during the study. Horvath-EAA was significantly higher at baseline in participants with clinical events (P = .027). After adjusting for confounders, we found a trend toward an association of higher levels of all EAA measures at baseline with serious clinical events. CONCLUSIONS: Epigenetic aging did not accelerate in long-term aviremic HIV-infected adults after 4 years of successful ART. EAA measures deserve further study as potential tools for predicting clinical events.