MACS/WIHS -CCS-Supplement

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PROJECT ABSTRACT FY 2022 OAR Strategic Funds are requested to perform a detailed investigation of the relationship of the oral microbiome, immune response, and HIV to chronic obstructive pulmonary disease (COPD). COPD, including airway obstruction and emphysema, is an increasing health problem in people with HIV (PWH) even in the current era of antiretroviral therapy (ART). Our preliminary data suggest that the oral microbiome is associated with lung function, but we lack a detailed understanding of the role of particular microbial communities and the potential mechanisms underpinning the association, which currently impedes development of intervention strategies. We will utilize oral data, microbiome analyses, blood specimens, and pulmonary function measures already being collected throughout MWCCS in visits 102 and 103 in order to analyze the relationship of oral health and the oral microbiome to lung function. We will also perform measurements of peripheral cytokines, inflammatory responses, and the oral cavity environment to assess potential mechanisms linking the microbiome to lung health. These investigations will be performed in all individuals who have completed pulmonary function testing across MWCCS. We will then perform detailed oral evaluations and collect microbial samples from multiple oral niches in a subset of participants to better delineate relationships of specific oral health components and lung function at Pitt and UNC. Using a novel technique to identify immunoglobulin-bound bacteria and fungi, we will identify key microbes that drive host response and are related to COPD. These investigations will identify potentially modifiable targets contributing to COPD in PWH. We will address NIH high priority AIDS-designated topics of: 1) a common and high-burden HIV- associated comorbidity; 2) interdisciplinary collaborations among experts in pulmonary disease, microbiome, dental medicine, and analytics; 3) disparities in HIV given impact of social determinants of health on both lung function and oral health; 4) fundamental discovery in cross-cutting science; and 5) training the next generation of HIV investigators. These investigations will build on the previous research conducted by the MWCCS and provide insight into a novel mechanism of HIV-associated lung disease with potential to develop new interventions to modulate the oral microbiome to improve pulmonary function.