Longitudinal Trajectories of Physical and Cognitive Function among Persons Aging with HIV

Older persons with HIV (PWH) experience high rates of cognitive impairment and accelerated declines in function compared to the general population. Such functional status declines have been associated with significant morbidity and mortality in among PWH. In the general elderly population, longitudinal dynamic relationships between physical and cognitive function have been identified. In PWH, cross-sectional associations between impaired cognition and physical function have been previously noted, but longitudinal trajectories of cognitive and physical function and how they relate to one another have not been evaluated. Metformin has shown promise as a senolytic agent. Clinical trials are underway to investigate use of metformin in preventing age-related declines in among elderly adults without HIV. This proposal will investigate the longitudinal relationship between cognitive and physical function in PWH and assess the potential impact of metformin on these trajectories. The proposed study will utilize data available from three large prospective, observational cohorts of men and women with or at risk for HIV. This investigation will be the first to comprehensively examine longitudinal associations between cognitive and physical function in a large group of PWH and assess the impact of metformin therapy on these outcomes in PWH. These results can inform the focus and ideal timing of interventions, such as a formal clinical trial of metformin, to prevent cognitive and physical function declines among older PWH. Moreover, this proposal aligns with the GEMSSTAR program’s mission to support a young investigator seeking to bridge aging and HIV research to improve care for older PWH.