Sexual minority (i.e., non-heterosexual) populations experience higher rates of mental health disorders and health related problems. Unique stressors such as discriminatory experiences, expectations of discrimination, internalization of social stigma, and concealment of sexual orientation, collectively termed “sexual minority stress”, are the primary explanatory model for these health disparities. The goal of this proposal is to build on the candidate’s demonstrated track record of bio-behavioral research with sexual minority populations by developing expertise and gaining meaningful pilot data on the relationship between epigenetic mechanisms (e.g., DNA methylation) and sexual minority stress among sexual minority men living with HIV. This mentored scientist award would facilitate research, training, and mentorship in epigenetics. The proposed study, executed over 12 months, will examine the relationship between sexual minority stress and DNA methylation related to functional inflammatory processes among sexual minority men living with HIV. Leveraging the infrastructure of an existing randomized controlled trial (K23DA039800; Flentje, PI), the cross-sectional associations among sexual minority stress and DNA methylation at baseline of this trial will be examined. Aim 1 will examine whether sexual minority stress is related to differentially methylated regions at sites functionally related to inflammation. Aim 2 will identify if networks of genes related to inflammation show differential patterns of perturbation between high and low minority stress groups. General linear models will test for differentially methylated regions for Aim 1 in models co-varying age, adjusting for multiple hypothesis testing. Aim 2 hypotheses will be tested using pathway enrichment analyses in conjunction with KEGG defined gene sets. The results will inform future work examining the social genomic determinants of health. Taken together, this research and mentorship plan will lay the foundation for future extramural funding examining longitudinal relationships between sexual minority stress and epigenetic changes, as well as which epigenetic markers may predict responsiveness to intervention.