BackgroundPersons living with human immunodeficiency virus (PLWH) face an increased burden of chronic obstructive pulmonary disease (COPD). Repeated pulmonary infections, antibiotic exposures, and immunosuppression may contribute to an altered small airway epithelium (SAE) microbiome.MethodsSAE cells were collected from 28 PLWH and 48 HIV- controls through bronchoscopic cytologic brushings. DNA extracted from SAE cells was subjected to 16S rRNA amplification and sequencing. Comparisons of alpha and beta diversity between HIV+ and HIV- groups were performed and key operational taxonomic units (OTUs) distinguishing the two groups were identified using the Boruta feature selection after Random Forest Analysis.ResultsPLWH demonstrated significantly reduced Shannon diversity compared with HIV- volunteers (1.82 ± 0.10 vs. 2.20 ± 0.073, p = 0.0024). This was primarily driven by a reduction in bacterial richness (23.29 ± 2.75 for PLWH and 46.04 ± 3.716 for HIV-, p < 0.0001). Phyla distribution was significantly altered among PLWH, with an increase in relative abundance of Proteobacteria (p = 0.0003) and a decrease in Bacteroidetes (p = 0.0068) and Firmicutes (p = 0.0002). Six discriminative OTUs were found to distinguish PLWH from HIV- volunteers, aligning to Veillonellaceae, Fusobacterium, Verrucomicrobiaceae, Prevotella, Veillonella, and Campylobacter.ConclusionsCompared to HIV- controls, PLWH’s SAE microbiome is marked by reduced bacterial diversity and richness with significant differences in community composition.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0835-7) contains supplementary material, which is available to authorized users.