Distinct lung microbiota associate with HIV-associated chronic lung disease in children

Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in Sub-Saharan Africa, but risk factors for CLD are poorly understood. We hypothesized that distinct airway microbiota exist and differentially relate to the risk of CLD among 202 HIV-infected children aged 6-16 years in Harare, Zimbabwe. We defined CLD by clinical, spirometric, or radiographic criteria, and determined sputum microbiota composition using 16S ribosomal RNA V4 gene region sequencing. Around two fifths of children had CLD according to our definition. Dirichlet multinomial mixtures identified four compositionally distinct sputum microbiota structures. Patients whose sputum microbiota was dominated by Haemophilus, Moraxella or Neisseria (HMN) were at 1.5 times higher risk of CLD than those with Streptococcus or Prevotella (SP)-dominated microbiota (RR=1.48, p=0.035). Cell-free products of HMN sputum microbiota induced features of epithelial disruption and inflammatory gene expression in vitro, indicating enhanced pathogenic potential of these CLD-associated microbiota. Thus, distinct sputum microbiota exist in HIV-positive children and adolescents on ART in Sub-Saharan Africa, with those dominated by Haemophilus, Moraxella or Neisseria associated with enhanced pathogenesis in vitro and increased risk of CLD within the population studied. Future studies are needed to histologically validate a microbiota-informed characterization of HIV-CLD and characterize in vivo metabolome function.