C27-16 Relationship Between Epithelial Barrier Disruption, Fungal Translocation, Inflammation and Pulmonary Function in People With HIV

Background Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a comorbidity among people with HIV (PWH), yet its pathogenesis in this population remains unclear. One proposed mechanism involves fungal translocation due to compromised epithelial barriers, which may drive systemic inflammation and contribute to pulmonary dysfunction in PWH. Objectives To explore the relationship between epithelial barrier integrity, fungal translocation, systemic inflammation, and pulmonary function in PWH. Methods Sixty-one participants from the Pittsburgh HIV Lung Cohort underwent pulmonary function testing (PFTs). Plasma levels of 25 biomarkers related to epithelial integrity and inflammation were measured. Fungal composition in oral, sputum and stool samples was assessed using ITS sequencing. Circulating fungal components were quantified via plasma 1,3-beta-D-glucan (BDG). Variables were categorized into covariates (age, sex, smoking status), biomarkers, fungal ITS taxonomic abundances and PFT measures. Principal component analysis (PCA) was used for cytokine selection, and linear regression models evaluated inter-variable associations and predictors of pulmonary function. Results All participants were PWH, with 85% male and 48% Caucasian, and a mean age of 53 years. All individuals were receiving antiretroviral therapy (ART), and 89% had undetectable plasma HIV RNA levels. A history of cigarette smoking was reported by 64% of participants. The median CD4+ cell count was 610 cells/µL (IQR: 491). PFT assessments showed a mean post-bronchodilator FEV1pp of 87% (SD: 18%), FVCpp of 93% (SD: 15%), FEV1/FVC ratio of 73% (SD: 10%), and DLCOpp of 76% (SD: 18%). Plasma BDG levels were positively correlated with inflammatory markers sCD14, CCL2 and IL-10. Biomarkers indicative of epithelial barrier disruption—such as RAGE, FABP2, REG3α and Zonulin—were associated with increased systemic inflammation and inversely related to lung function. IL-6 showed a negative association with DLCOpp, while CCL17 and sCD163 were inversely correlated with both FEV1pp and FVCpp. BDG levels were linked to IL-6 and oral Ascomycota Alternaria. In sputum samples, Xylodon and Robbauera were positively associated with FVCpp, whereas Cutaneotrichosporon was negatively associated. Oral Candida was inversely related to FEV1pp, DLCOpp, and FVCpp, while fungal communities in stool samples were not correlated with PFT measures. Conclusions Circulating BDG was associated with systemic inflammation and shifts in fungal composition. Disruption of epithelial barrier integrity may alter fungal ecology, enhance systemic inflammation and lead to pulmonary function decline in PWH despite effective ART. Abbreviation: ITS: internal transcribed spacer; REAG: Receptor for advanced glycation end products; FABP2: intestinal fatty acid binding protein; REG3α: regenerating islet-derived protein 3α.