Cohort Studies of HIV/AIDS and Substance Use in Miami - This is a proposal for the continuation of the well-characterized Miami Adult Studies on HIV (MASH) cohort of middle-to-old, aged people living with and without HIV and substance use followed biannually, with a history of multidisciplinary collaboration. After 3% yearly dropout, MASH (n=1,439) has people living with HIV & cocaine use (n=231), HIV & no cocaine use (n=445), no HIV with cocaine use (n=324), and no HIV with no cocaine use (n=439), followed biannually. The MASH infrastructure has accrued >8,000 visits, >500,000 biospecimens, >900 MRI scans, microbiome and epigenetic data, and a database of >6,000 variables on HIV, substance use, structural factors, and comorbidities. As the only NIDA HIV Cohort in the South, our work addresses NIH-HIV research priorities on the intersection of HIV and substance use, specifically cocaine, which is widely used by people living with HIV (PLWH), and comorbidities including neurocognitive impairment (NCI) and physical frailty, a phenotype of physiological deterioration linked to disability and mortality. We propose to expand the MASH cohort to 1,879 people to increase representation of women while following the participants for HIV, substance use patterns, emergent comorbidities, and poly-social risk. With the new recruitment, MASH will become a cohort of predominantly women, representing a population lacking among NIDA cohorts, yet remains impacted by HIV and substance abuse. The scientific aims of this proposal involve epigenetic, neuroimaging, and neurocognitive patterns of cognitive frailty, and are to (1) longitudinally investigate differential epigenetic patterns in people living with and without HIV and cocaine use that predict cognitive frailty. Epigenetic modifications, an interface between the genome and environment, are associated with HIV, drug abuse, physical frailty, NCI, and social factors, and can predict health outcomes, yet remain understudied in the context of HIV and substance use. Scientific aim (2) is to investigate whether the epigenetic signatures predict structural and functional neuroimaging patterns, which then can predict neurocognitive and physical components of cognitive frailty over time, considering sex and social risk. This work integrates the Health Promotion Research Center Framework to leverage existing relationships with end-users to bridge research and practice. Our goal is to implement research into actionable strategies such as colocation of HIV care and substance abuse treatment, identification of early cognitive frailty diagnostic markers, and prediction of clinical trajectories. By employing multimodal neuroimaging combined with epigenetics, neurocognitive, and physical frailty assessments, this project aims to enable precision medicine approaches in the context of cognitive frailty by identifying specific pathologies in PLWH with cocaine use. By leveraging the unique characteristics of MASH, this study has the potential to generate valuable insights into the interplay of HIV, cocaine use, and cognitive frailty, while the integration of implementation science will inform effective solutions.
