Enrichment of the airway microbiome in people living with HIV with potential pathogenic bacteria despite antiretroviral therapy

Abstract

Background: Long-term antiretroviral therapy (ART) enables people living with HIV (PLW-HIV) to be healthier and live longer; though they remain at greater risk of pneumonia and chronic lung disease than the general population. Lung microbial dysbiosis has been shown to contribute to respiratory disease. Methods: 16S-rRNA gene sequencing on the Miseq-platform and qPCR for typical respiratory pathogens were performed on sputum samples collected from 64 PLW-HIV (median blood CD4 count 676 cells/mL) and 38 HIV-negative participants.Finding: Richness and a-diversity as well as the relative-abundance (RA) of the major taxa (RA>1%) were similar between both groups. In unweighted-Unifrac ß-diversity, the samples from PLW-HIV showed greater diversity, in contrast to the HIV negative samples which clustered together. Gut bacterial taxa such as Bilophila and members of Enterobacteriaceae as well as pathogenic respiratory taxa (Staphylococcus, Pseudomonas and Klebsiella) were significantly more frequent in PLW-HIV and almost absent in the HIV-negative group. Carriage of these taxa was correlated with the length of time between HIV diagnosis and initiation of ART (Spearman-rho=0¢279, p=0¢028). Interpretation: Although the core airway microbiome was indistinguishable between PLW-HIV on effective ART and HIV-negative participants, PLW-HIV's respiratory microbiome was enriched with potential respiratory pathogens and gut bacteria. The observed differences in PLW-HIV may be due to HIV infection altering the local lung microenvironment to be more permissive to harbour pathogenic bacteria that could contribute to respiratory comorbidities. Prompt start of ART for PLW-HIV may reduce this risk.

Sputum Microbiome and Chronic Obstructive Pulmonary Disease in a Rural Ugandan Cohort of Well-Controlled HIV Infection

“…No participant reported the use of any recreational drugs ( Table 3 ). Our cohort results were compared to the sputum microbiome data from a UK-based HIV cohort ( 16 ). In this cohort, sputum samples were collected from 64 HIV-infected individuals with a median CD4 count of 676 cells/μL and 38 HIV-negative individuals.…”

“…The spirometric patterns were normal for most participants, with only 10 HIV-infected and two HIV-negative participants reported with COPD (defined as forced expiratory volume in 1 second [FEV 1 ]/Forced vital capacity [FVC] < 0.7). All participants were free of symptoms of acute respiratory illness at the time of recruitment ( 16 ).…”

“…Finally, we compared our results with sputum microbiome data from a UK-based HIV cohort ( 16 ). The recruitment criteria and the sequencing used in the UK cohort were similar to the ones used in our cohort.…”

“…We analyzed the sputum microbiota among COPD and HIV-infected individuals with this aim. Finally, we compared our results with sputum microbiome data from a UK-based HIV cohort to identify geographical characteristics of microbial composition ( 16 ).…”

Pulmonary Immune Dysregulation and Viral Persistence During HIV Infection

“…Impaired lung immune function and HIV reservoir expansion are likely amplified through exacerbated inflammation caused by microbial dysbiosis in the lung and gut of PLWH (145,(205)(206)(207)(208). Although the gastrointestinal and respiratory tracts are separate organs, they share a common mucosal immune system known as the gut-lung axis (209).…”