Impact of long-term azithromycin treatment on the respiratory microbiome in HIV-associated chronic lung disease

Obliterative bronchiolitis is a recently diagnosed chronic lung disease (CLD) detected in 30% of older children and adolescents living with HIV in Sub-Saharan Africa. Although there are no management guidelines, long-term azithromycin has been suggested as a treatment option due to its dual antimicrobial and immunomodulatory action and effectiveness in other CLDs such as cystic fibrosis, bronchiectasis and asthma. However, its effect on the respiratory bacterial community in this disease context remains unknown. Therefore, this study aims to investigate the impact of 48 weeks of once-weekly, weight-based dosing of azithromycin on the respiratory microbiome of children and adolescents with HIV-associated CLD in an individually randomised, placebo-controlled, double-blinded clinical trial in Zimbabwe and Malawi. We also assessed the persistence of the azithromycin effect on the respiratory microbiome six months post-intervention. Finally, we evaluated the differences in the respiratory microbiome of HIV-infected children with and without CLD. This study's findings extend our understanding of the pathogenesis of this novel CLD and the mechanisms underlying the effectiveness of azithromycin.