Abstract
Chronic obstructive pulmonary disease (COPD) is increasingly recognized among people living with HIV in sub-Saharan Africa, yet the mechanisms linking airway microbial ecology to chronic inflammation remain poorly understood. Here, we study 200 adults stratified by HIV and COPD status, including 160 participants with two-year longitudinal follow-up, using an integrated multi-omics framework combining sputum 16S rRNA profiling, bacterial outer membrane vesicle quantification, airway cytokine profiling, CyTOF immune phenotyping, bulk transcriptomics of induced sputum, bronchoalveolar lavage and peripheral blood, and bronchoalveolar lavage single-cell RNA sequencing-guided deconvolution. We find that sputum microbial communities are shaped predominantly by temporal ecological turnover rather than HIV or COPD status. Although microbial diversity, microbiome instability, outer membrane vesicle burden and inferred airway cellular composition remain largely preserved, HIV-associated COPD exhibits disease-specific microbial signatures together with inflammatory transcriptional remodeling concentrated in induced sputum. Integrated analyses identify selective host-microbe interaction networks linking discrete microbial taxa with inflammatory, immune and transcriptional programmes.