Longitudinal Study of HIV and Aging in Brazil

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PROJECT SUMMARY This study will investigate the clinical outcomes and immunometabolism consequences associated with gut microbiome profiles in older people living with HIV. Adverse shifts in the gut microbiome have been associated with chronic non-communicable diseases (particularly cardiovascular disease [CVD]) and HIV infection. Composition of the gut microbiome is also associated with measures of healthy aging and development of frailty, sarcopenia, and cognitive decline in aging adults. Our understanding of how the gut microbiome and its potential immune and metabolic pathways contribute to the excess burden of CVD and geriatric syndromes in older adults with HIV is incomplete. This data is particularly needed from global settings where differences in HIV disease history, endemic co-infections, and social and economic settings shape the microbiome composition. Using previously collected samples from a large, longitudinal cohort study of aging adults with HIV in Brazil, this study will examine (1) the microbiome composition and functional profiles associated with CVD and geriatric syndromes and (2) the microbiome metabolites associated with inflammatory pathways which contribute to those conditions. Leveraging the rich clinical and social data collected in the Longitudinal Study of HIV and Aging in Brazil (R01AG071439), we will first characterize the gut microbiome composition of all participants (n=700) to examine how the microbiome profiles predict prevalent CVD and geriatric syndromes, after accounting for confounders such as age, HIV disease biomarkers (including CD4 cell count nadir), presence of chronic co-infections, and socioeconomic factors. In a nested cohort (n=90 participants), we will examine more specifically whether the presence of pro-inflammatory microbiome species predicts prevalent CVD and geriatric syndromes using cutting-edge, molecular genomic approaches. Finally, to explore potential immunometabolism mechanisms of gut dysbiosis and CVD and geriatric syndromes, we will measure whether alterations in plasma microbiome metabolites (amino acids and short chain fatty acids) predict elevations in specific inflammatory pathways associated with CVD and geriatric syndromes in adults with HIV. Building upon a robust, international collaborative study exploring how chronic co-infections affect aging outcomes in adults with HIV, this supplemental study adds the important examination into the role of commensal microbes. The supplemental study will be led by key study co-investigators and further enrich the collaborative network across the hemisphere.