Abstract 4365616: Premature Aging is Associated with Abnormal Cardiac Function in Perinatally HIV-Infected Young Adults

Introduction: Children and adolescents with perinatally acquired HIV (PHIV) are now surviving into adulthood due to improved antiretroviral therapy. However, many still face an increased risk of cardiovascular (CV) disease and accelerated biological aging, as indicated by epigenetic biomarkers. Research Questions: Young adults with PHIV will exhibit epigenetic age acceleration, which is associated with alterations in CV structure and function. Aims: To quantify the epigenetic age in monocytes associated with CV function in young adults with PHIV and those who are HIV-exposed uninfected (PHEU) participants of the Adolescent Master Up Protocol (AMP) conducted by the NIH Pediatric HIV/AIDS Cohort Study (PHACS) network. Methods: 123 U.S. young adults (75 PHIV and 48 PHEU) underwent echocardiography and provided monocyte DNA samples for epigenetic analysis. We calculated five epigenetic clocks, with a focus on GrimAge (based on DNA methylation markers of inflammation and metabolic conditions and predicts mortality and health span age-related conditions, including CV risk). We investigated the associations between GrimAge, cardiomyopathy [defined by left ventricular (LV) ejection fraction (LVEF) z-score<-2], and echocardiographic measures, including LVEF and LV mass-to-volume z-scores. Results: PHIV and PHEU exhibited elevated GrimAge relative to their chronological age (PHIV and PHEU mean ages: 23.4 and 22.1 yrs, respectively, mean GrimAge acceleration +17.85 and +15.76 yrs, respectively). Young adults with PHIV, with cardiomyopathy had a higher mean GrimAge (45.7 yrs) than those without cardiomyopathy (40.2 yrs). Regression analyses revealed a significant negative association between GrimAge and the LVEF z-score (slope: –0.30 per 5-year increment in GrimAge, p=0.028), indicating that individuals with a more advanced “biological age” had lower LV systolic function. Additionally, GrimAge showed a positive, but not statistically significant, association with LV mass-to-volume ratio (slope: +0.32, p=0.16), indicating a possible trend toward altered LV structure in individuals with older GrimAge. Conclusion: Young adults with PHIV or PHEU demonstrated premature epigenetic aging when compared to their chronologic age. This was associated with reduced LVEF and potential LV structural remodeling, as indicated by a higher LV mass-to-volume ratio. These findings underscore the value of epigenetic aging measures as potential surrogate endpoints for future adverse CV health in PHIV populations.