AWARE Project 1: Impact of unhealthy alcohol use, HIV reservoirs, and social disadvantage on candidate biomarkers of inflammaging

Yale University, New Haven CT

Investigators

Abstract

AWARE PROJECT 1 (BIOMARKERS) The concept of inflammaging brings together biological phenomena accentuated in people aging with HIV (i.e., chronic inflammation, immune dysfunction, comorbid disease). The Alcohol Harm Paradox (see Overall grant) suggest that those living in socio-economically disadvantaged communities may experience more inflammaging than those without these exposures. Our goal is to better understand the biology underpinning how exposure to unhealthy alcohol use and socio-economically disadvantaged communities contribute to inflammaging in the context of HIV infection. We propose a novel operationalization of inflammaging relevant to people with HIV comprising biological age acceleration, HIV reservoir size, and embodied social adversity. Our approach recognizes and seeks to describe the multiple, interacting, biological effects of these complex exposures. We anticipate that the findings will provide biological insights on inflammaging that may help tailor future interventions to promote healthier aging in people with HIV (PWH). Biological age acceleration, occurs when the rate of biological aging exceeds that of chronological aging and is associated with morbidity and mortality. No established biological age estimator (clock) targets inflammaging. Aim 1 will determine the association of unhealthy alcohol use and biological (multi-omic) age acceleration including biological aging estimated using a novel inflammation-derived clock. HIV latency and resulting persistence in cellular reservoirs drives and is driven by inflammation and immune activation and are the major obstacles to curing HIV. Yet, despite known immunomodulatory effects of alcohol, the relationship of alcohol and HIV reservoir size has not been studied. Aim 2 will determine the association of A) alcohol use and HIV reservoir size in CD4+ T-cells; and B) HIV reservoir size and biological age acceleration in people with HIV. Conserved Transcriptional Response to Adversity (CTRA) expression is a pattern of dysregulated immunologic/inflammatory gene expression profiles observed in those with extended exposures to adverse environmental conditions (e.g., poverty, chronic stress). How alcohol use alters CTRA expression is poorly understood generally and in the context of HIV. Aim 3 will explore A) the association of alcohol use and CTRA expression; B) the correlates of CTRA expression in PWH including socioeconomic deprivation; and C) association of CTRA and biological age acceleration. Our work paves the way for future mechanistic studies explaining how unhealthy alcohol use causes negative health consequences among PWH. This body of work will also identify novel biomarkers of inflammaging relevant in future alcohol intervention studies in the context of HIV.