Epigenetic Aging and Associated Factors in Japanese People with HIV: A Protocol for a Single-Center Cross-Sectional Study

Background: Advances in antiretroviral therapy (ART) have transformed human immunodeficiency virus (HIV) infection into a manageable chronic condition. However, people with HIV (PWH) face an increased burden of age-related non-AIDS-defining illnesses. Epigenetic age (EA) and epigenetic age acceleration (EAA), based on DNA methylation, have emerged as objective indicators of biological aging. Although studies in Western countries suggest that EAA levels are elevated in PWH and may decline after ART initiation, evidence in the Japanese population remains scarce. This study aims to characterize EA and EAA in Japanese PWH and to evaluate their associations with the duration of ART, cumulative exposure to specific drug classes, frailty, lifestyle factors, and immunological, metabolic, and inflammatory markers. Methods: This single-center, cross-sectional study involves 100 adult Japanese males with HIV who have received ART for at least 12 months. EA and EAA will be calculated using whole-blood DNA methylation data generated using the Illumina Infinium MethylationEPIC v2.0 BeadChip array and epigenetic clocks developed on Japanese populations. Linear regression models will be used to evaluate the associations between EAA and the factors collected from medical records, laboratory tests, self-administered questionnaires, and comorbidities. Discussion: This study provides baseline data for future longitudinal and comparative studies. The integration of clinical, questionnaire, and omics data facilitates the exploration of biological mechanisms underlying aging in this population. The limitations include the cross-sectional design, which precludes causal inference and the lack of a control group.