Effect of advanced HIV infection on the respiratory microbiome

Rationale: Previous work found the lung microbiome in healthy subjects infected with HIV was similar to that in uninfected subjects. We hypothesized the lung microbiome from subjects infected with HIV with more advanced disease would differ from that of an uninfected control population. Objectives: To measure the lung microbiome in an HIV-infected population with advanced disease. Methods: 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from30subjects infectedwithHIV with advanced disease (baseline mean CD4 count, 262 cells/mm³) before and up to 3 years after starting highly active antiretroviral therapy (HAART) and compared with 22 uninfected control subjects. Measurements and Main Results: The lung microbiome in subjects infected with HIV with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared with uninfected BAL. Differences improved with HAART, but still persisted up to 3 years after starting therapy. Population dispersion in the group infected with HIV was significantly greater than in the uninfected cohort and declined after treatment. There were differences in the relativeabundanceofsomebacteria between the two groupsat baseline and after 1 year of therapy. After 1 year on HAART, HIV BAL contained an increased abundance of Prevotella and Veillonella, bacteria previously associated with lung inflammation. Conclusions: The lung microbiome in subjects infected with HIV with advanced disease is altered compared with an uninfected population both in diversity and bacterial composition. Differences remain up to 3 years after starting HAART. We speculate an altered lung microbiome in HIV infection may contribute to chronic inflammation and lung complications seen in the HAART era.