Pneumonia Surveillance in Ugandans with HIV Through the Lens of Culture-Independent Metatranscriptomics: A Cross Sectional Study

Background: Pneumonia is a leading cause of death worldwide and is a major healthcare challenge for HIV-infected persons. Despite this, the etiology of pneumonia in this population remains poorly understood.Methods: We employed a combination of bulk RNA sequencing of bronchoalveolar lavage fluid and standard culture- and PCR-based diagnostics to survey the landscape of transcriptionally active respiratory pathogens in 217 Ugandan patients with HIV who were hospitalized for pneumonia.Findings: A microbiologic diagnosis was obtained in 211 (97.2%) of individuals, with at least one microorganism of established respiratory pathogenicity identified in 113 (52.1%) of patients, and a microbe of possible pathogenicity identified in 94 (47.9%) of patients. Mycobacterium tuberculosis (MTB) was the most commonly identified established pathogen in 35 (16.1%) of the patients and bacterial or viral co-infections were found in 13 (37.2%) of MTB-positive individuals. Streptococcus mitis, not previously reported as a cause of pneumonia in patients with HIV, was the most commonly identified bacterial organism (n=37, 17.1% of patients), and Hemophilus influenzae was the most commonly identified established bacterial pathogen (n=20, 9.2% of patients). Pneumocystis jirovecii, Hemophilus influenza, human rhinovirus, Streptococcus species and Veillonella species were more prevalent in patients with a CD4 T-cell count of <200 cells/uL. Streptococcus species, human herpes virus 4, and Veillonella species were associated with increased 70-day mortality.Interpretation: We advance understanding of the microbiologic landscape of lower respiratory tract infections in the vulnerable demographic of persons living with HIV in a representative and understudied sub-Saharan African region.