Abstract Chronic obstructive pulmonary disease (COPD) is increasing in prevalence among people living with HIV (PLWH) as widespread use of Antiretroviral Therapy (ART) has increased longevity in this population. In rural Ugandan ART clinics, we report COPD prevalence of 6.22%. Currently, it’s not fully known what drives chronic lung inflammation in PLWH despite being virologically suppressed on ART. There is need to explore factors driving chronic airway inflammation among PLWH. Airway microbiome has been implicated in the pathogenesis of COPD. Using 16S ribosomal RNA gene (rDNA) sequencing on induced sputum samples from 200 adults with equal numbers of participants by HIV and COPD status in our rural Ugandan cohort, we show that among PLWH, airway enrichment with Staphylococcus spp as well as depletion of Pseudopropionibacterium and Porphyromonas spp are associated with COPD. Currently, we don’t fully understand how such genera drive chronic airway inflammation. In this study, we will determine the association between lung microbiome and immune responses (particularly Th17/Treg responses) in the distal airways of PLWH with COPD in a viremically controlled Ugandan cohort using BAL samples. We hypothesize that: (i) a Th17-driven pro-inflammatory immune response predominates in the distal airways of PLWH with COPD and (ii) specific distal airway microbial species (signatures) are associated with Th17-immune response among PLHW with COPD. In this study, we will determine (1): the distal airway immune profile among individuals with HIV and COPD in Uganda and (2) the association between lung microbiome and distal airway immune responses using BAL samples.

Project Narrative World over, a significant reduction in HIV-associated mortality has substantially increased life expectancy, with estimates among people living with HIV (PLWH) now approaching that of the general population. Consequently, there has been increased attention among survivors to the emerging global burden of non- communicable diseases such as chronic obstructive pulmonary disease (COPD). Sub-Saharan Africa, with the highest density of PLWHA, has experienced dramatic increases in COPD related morbidity and mortality. It’s not fully known what drives chronic lung inflammation in PLWHA population well-controlled on ART. In this grant proposal, we will determine the association between lung microbiome and immune responses (particularly Th17/Treg responses) in the distal airways of PLWH with COPD in a viremically controlled Ugandan cohort using bronchoalveolar lavage (BAL). This study will be conducted in a setting with a high prevalence of people living with HIV (PLWH) and COPD. Understanding the relationship between lung microbiome and the orchestrated immune responses (particularly Th17/Treg responses) in the distal airways of PLWH with COPD will provide insight into the role of lung microbiome and mechanisms of COPD among PLWH.