Abstract
BackgroundIn the BREATHE trial weekly azithromycin decreased the rate of acute respiratory exacerbations (AREs) compared to placebo among children and adolescents with HIV-associated chronic lung disease (CLD) taking antiretroviral therapy (ART). The aim of this analysis was to identify risk factors associated with AREs and mediators of the effect of azithromycin on AREs.MethodsThe primary outcome of this analysis was the rate of AREs by study arm up to 49 weeks. We analysed rates using Poisson regression with random intercepts. Interaction terms were fitted for potential effect modifiers. Participants were recruited from Zimbabwe and Malawi between15 June 2016 and 4 September 2018.FindingsWe analysed data from 345 participants (171 allocated to azithromycin and 174 allocated to placebo). Rates of AREs were higher among those with an abnormally high respiratory rate at baseline (adjusted rate ratio (aRR) 2.08 95% CI 1.10-3.95 p-value 0.02) and among those with a CD4 cell count <200 cells/mm3 (aRR 2.71; 95% CI 1.27-5.76; p-value 0.008). We found some evidence for variation in the effect of azithromycin by sex (p-value for interaction=0.07); males had a greater reduction in the rate of ARE with azithromycin treatment than females. We found that azithromycin had a greater impact on reducing AREs in participants with chronic respiratory symptoms at baseline, those on 1st line ART, with a FEV1 score >-2 and participants without baseline resistance to azithromycin. However, there was no statistical evidence for interaction due to low statistical power.InterpretationThese may represent subgroups who may benefit the most from treatment with weekly azithromycin, which could help guide targeted treatment.FundingThere was no funding source for this post hoc analysis.
Highlights
IntroductionThe scale-up of paediatric antiretroviral therapy (ART) has resulted in a dramatic increase in survival such that children who would have died in infancy or early childhood are surviving to
The scale-up of paediatric antiretroviral therapy (ART) has resulted in a dramatic increase in survival such that children who would have died in infancy or early childhood are surviving to Research in contextEvidence before this studyAt present little evidence exists on the management of chronic lung disease (CLD) in children and adolescents with Human immunodeficiency virus (HIV)
Adjusted random effects Poisson regression models were used to explore whether the effect of azithromycin on acute respiratory exacerbations (AREs) was modified by baseline risk factors including age group, sex, forced expiratory volume in 1 second (FEV1) Z-score, CD4 cell count, HIV viral load (VL), history of treatment for TB, weight-for-age Z-score, height-for-age Z-score, presence of cough and tachypnoea, and carriage of azithromycinresistant bacteria, and time variables
Summary
The scale-up of paediatric antiretroviral therapy (ART) has resulted in a dramatic increase in survival such that children who would have died in infancy or early childhood are surviving to. The BREATHE trial found that treatment with weekly azithromycin for 48 weeks did not result in improved lung function but did significantly lower the risk of acute respiratory exacerbations In this post hoc analysis of the BREATHE trial we examined risk factors for acute respiratory exacerbations (AREs), and factors that modify the association between weekly azithromycin and risk of AREs. We found that a baseline abnormally high respiratory rate and CD4 count
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