This Project Grant award of $2,331,737 from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) will fund a comprehensive study to investigate the impact of methamphetamine (MA) use on HIV persistence, immune dysfunction, and clinical outcomes among people living with HIV (PWH) on antiretroviral therapy (ART). The study will leverage three unique cohorts to perform the first-in-human investigations directly quantifying MA concentrations in blood, cerebrospinal fluid, and tissues of PWH on ART, and relate these to measures of HIV persistence, host inflammation, and organ damage in the central nervous and cardiovascular systems. The award will support the use of innovative techniques, including whole-body PET imaging, multi-omic assays, and high-resolution reservoir analyses, to provide a detailed pathophysiological understanding of the additive effects of MA and HIV on clinical morbidity. This research aims to identify novel therapeutic targets to reduce immune dysfunction, HIV persistence, and inflammation in PWH with MA use, ultimately improving chances of HIV cure in this population.
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