Study title: Bronchopulmonary function in response to azithromycin treatment for chronic lung disease in HIV-infected Children (BREATHE)

Lead Researcher(s)

Rashida Ferrand, Jon Odland, Liz Corbett,  Grace Mchugh, Sarah Rowland-Jones

Funder(s)

GLOBVAC, Medical Research Council of Norway

Partner(s)

London School of Hygiene and Tropical Medicine, University of Zimbabwe, Malawi-Liverpool Wellcome Trust Clinical Research programme, University of Oxford, University of Cape Town, The Arctic University of Norway

Background

HIV-associated chronic lung disease (HCLD) in children is associated with small airways disease, is common despite antiretroviral therapy (ART), and is associated with substantial morbidity. Azithromycin has antibiotic and immunomodulatory activity and the hypothesis was that azithromycin may be effective in treating HCLD through reducing respiratory tract infections and inflammation.

Study aim(s)

To investigate the impact of weekly azithromycin treatment on lung function and morbidity in children with HIV-associated chronic lung disease.  

Study design

BREATHE was a double-blind, placebo-controlled randomised clinical trial conducted in Zimbabwe and Malawi of weekly azithromycin among children with HIV established on antiretroviral therapy children who are stable on antiretroviral therapy who have chronic lung disease.

400 children with HIV aged 6-16 years with a CLD (defined as Forced Expiratory Volume in 1 second (FEV1) z score<-1 were randomised 1:1 to weekly weight-based azithromycin or placebo for 12 months. The primary outcome was the mean difference in FEV1 z score. Secondary outcomes included acute respiratory exacerbations, all-cause hospitalizations and mortality.

Laboratory sub-studies included the effect of azithromycin on antimicrobial resistance, the diversity and composition of the respiratory and gut microbiome and on biomarkers of systemic inflammation.

Study dates

Sept 2014-Dec 2020