Weekly azithromycin for 48 weeks impacts nasopharyngeal microbial prevalence and Streptococcus pneumoniae serotypes in children with HIV-associated chronic lung disease

HIV-associated chronic lung disease (HCLD) accounts for over 50% of deaths in children living with HIV. Azithromycin reduces the risk of respiratory exacerbations in children with HCLD, but its impact on respiratory pathogens and Streptococcus pneumoniae serotypes in HCLD remains partially understood. We investigated the impact of azithromycin on the prevalence and density of respiratory microbes in children enrolled in the BREATHE randomized controlled trial. Nasopharyngeal swabs collected from 287 participants at baseline, 48 and 72 weeks were analysed using nanofluidic qPCR testing for 94 S. pneumoniae serotypes, 12 bacterial species, and eight respiratory viruses. No differences were observed between microbial colonisation in the azithromycin and placebo groups at baseline or 72 weeks. At 48 weeks, overall bacterial colonisation was significantly lower in the azithromycin group compared to placebo (adjusted Odd Ratio [aOR]: 0.45, 95% CI 0.25-0.82; p=0.008), with reduced colonisation of S. pneumoniae (aOR: 0.37; 95% CI: 0.24-0.71; p=0.003) and non-typeable Haemophilus influenzae (aOR: 0.29; 95% CI: 0.14-0.61; p=0.001). The 13-valent pneumococcal conjugate vaccine serotypes (19F and 23F) and non-vaccine type (15A/F) were most commonly observed in both groups at all time points. Findings suggest that azithromycin reduces nasopharyngeal colonisation of certain bacteria in HCLD during treatment but has no long-lasting effects after treatment cessation.Trial registration: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112, registered date: 24/04/2015).