Cannabis Use and Proximal Immune Dysregulation (CUPID)

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PROJECT SUMMARY/ABSTRACT Background. Black sexual minority men (SMM) experience profound HIV-related disparities compared to non- Hispanic White men, acquiring age-related diseases with greater symptom severity earlier in the life course and dying from HIV infection at higher rates. Early life exposure to stress is linked to key biological processes, specifically inflammation and shorter leukocyte telomere length, which are associated with HIV-related comorbidities and age-related diseases. It is well documented that young Black SMM experience multilevel sexual minority stress, such as sexual identity concealment, victimization, and community homophobia - products of stigma which further complicate health outcomes. Thus, understanding factors that may attenuate the effects of inflammation in younger ages is a critical period to mitigate HIV-related disparities later in life. Cannabis use is a noteworthy modifiable factor for investigation, given the substantial evidence of its role in anti- inflammatory processes and its rapidly accelerating legal and social acceptance; however, the rigor of prior research examining the influence of cannabis on inflammation and other key biological processes is limited because studies have mostly been cross-sectional, used self-reported measures of cannabis use, and are not generalizable to young Black SMM with HIV. To address these gaps, this K23 proposal – Cannabis Use and Proximal Immune Dysregulation (CUPID) – will fortify my Career Development efforts to (1) understand how biomarkers of cannabis may influence inflammation and leukocyte telomere length and (2) examine the modifying role of multilevel sexual minority stress. This K23 proposal will chart a pathway to achieve my long- term Career Goals of becoming an R01-funded investigator with expertise in multilevel determinants of biobehavioral processes underpinning HIV-related health disparities to guide the development of interventions with Black SMM with HIV. To accomplish my career goals, I will need training (1) to develop a comprehensive understanding of biomarkers of cannabis use, inflammation, and leukocyte telomere length; (2) to advance my understanding of multilevel sexual minority stress assessment in Black SMM; and (3) to develop expertise in analyzing longitudinal data. An accomplished, interdisciplinary Mentorship Team committed to supporting my transition to an independent investigator will provide guidance on the training and research activities. Specific Aims are (1) to determine the relationship between cannabis use and biomarkers of inflammation and leukocyte telomere length; and (2) to evaluate whether individual- interpersonal- community- and societal level sexual minority stress moderate the relationship of cannabis with inflammation and leukocyte telomere length. CUPID will inform the development of an R01 proposal for a more definitive cohort study to further elucidate the bio- behavioral pathways whereby cannabis use, and sexual minority stress are linked to inflammation and leukocyte telomere length in Black SMM with HIV.