Investigating the role of altered lung microbiome in fueling Th17 mediated airway inflammation in COPD among HIV-infected individual

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Abstract Chronic Obstructive Pulmonary Disease (COPD) is increasing in prevalence among people living with HIV (PLWH) as the widespread use of antiretroviral therapy (ART) has increased longevity in this population. With the highest density of PLWH, Sub-Saharan Africa has experienced dramatic increases in COPD-related morbidity and mortality. Despite viral suppression, it’s not fully known what drives accelerated lung function decline in this population. Amidst intense exposure to environmental insults, the airways have developed robust protective mechanisms which preserve the airway microenvironment, with highly specialized lung-resident innate and adaptive immune cells fighting off pathogens. However, these protective mechanisms deteriorate with age, resulting in a progressive decline in lung function and COPD development. This decline is worse in the setting of chronic HIV infection. Despite a lack of conclusive evidence, persistent airway immune activation among PLWH possibly drives airway immunosenescence, inflammaging, and progressive lung function decline. It is probable that in the setting of chronic HIV, contraction of the T-cell immune repertoire (immune diversity) increases susceptibility to infections, which drives chronic inflammation, immune exhaustion, and senescence. In this supplementary application, we aim to investigate the effect of HIV on distal airway immunosenescence and inflammaging among individuals with COPD. We hypothesize that: (1) chronic HIV infection accelerates age-dependent contraction of airway T cell receptor diversity; (2) and this reduced diversity is associated with airway inflammation and poor lung function (low FEV1 and FVC). We will use broncho-alveolar lavage samples from our currently running parent R21 study to; (1) determine the effect of chronic HIV on airway TCR diversity and (2) correlate airway TCR diversity indices with levels of inflammaging cytokines in BAL supernatant. This preliminary data will provide a basis to investigate airway inflammaging among PLWH, supplementing our parent R21 objectives of investigating the association between lung microbiome and immune profile in the distal airways of HIV-infected individuals with COPD in a viremically controlled Ugandan HIV cohort.