Pediatric patients with human immunodeficiency virus (HIV)-associated chronic lung disease (HCLD) receiving azithromycin (AZM) did not have improved lung function, but their risk for a first acute respiratory exacerbation (ARE) was significantly decreased. These findings from a double-blind, placebo-controlled, randomized clinical trial were published in JAMA Network Open.
The Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-Infected Children (BREATHE) study was conducted between 2016 and 2019 in Malawi and Zimbabwe among patients aged 6 to 19 years (N=347). Patients were randomly assigned in a 1:1 ratio to receive weekly weight-based dosing of oral AZM (n=173; 10-19.9 kg: 250 mg; 20-29.9 kg: 500 mg; 30-39.9 kg: 750 mg; ³40 kg: 1250 mg) or placebo (n=174) for 48 weeks. Participants were assessed for forced expiratory volume in 1 second (FEV1) and AREs at 2 weeks and every 12 weeks for the remainder of the study.
Participants had a median age of 15.3 years (interquartile range [IQR], 12.7-17.7), 51.0% were boys, baseline mean FEV1 z score was -2.00 (standard deviation [SD], 0.75). Treatment recipients were significantly younger (median 14.7 vs 15.8 years), fewer were female (46.2% vs 51.7%), and they had lower viral loads (median 2.5 vs 2.7 log10 copies/mL). Statistical analyses were adjusted for these baseline differences.
Adherence to the study protocol was higher among the AZM group (73.4% vs 67.2%), and 88.8% of participants were assessed for FEV1 at study conclusion. Mean FEV1 z scores were -1.90 (SD, 0.90) and -1.95 (SD, 0.91) among the AZM and placebo groups, respectively, corresponding with an adjusted mean difference of 0.06 (95% CI, -0.10 to 0.21; P =.48).
With a total follow-up time of 157 person-years among the AZM group and 154 person-years among the placebo group, AREs were observed among 9.2% of the AZM and 17.2% of the placebo recipients. Risk for first ARE among the AZM group compared with placebo was significantly decreased (hazard ratio [HR], 0.50; 95% CI, 0.27-0.92; P =.03).
Hospitalizations occurred among 1.2% of the AZM and 5.2% of the placebo cohorts. Total risk for hospitalizations was low (HR, 0.24; 95% CI, 0.06-1.07; P =.06). Three placebo recipients died. Malaria was diagnosed among 2 placebo recipients and 1 AZM recipient.
Few adverse events were observed; however, more patients receiving AZM reported minor gastrointestinal symptoms.
This study may have been limited by the low control over quality assessments by clinical staff at the study sites.
These data indicate AZM is an ineffective intervention for improving lung function among pediatric patients with HCLD, but that ARE events are reduced after AZM therapy.
Ferrand RA, McHugh G, Rehman AM, et al; BREATHE Trial Group. Effect of once-weekly azithromycin vs placebo in children with HIV-associated chronic lung disease: the BREATHE Randomized Clinical Trial. JAMA Netw Open. Published online December 17, 2020. doi:10.1001/jamanetworkopen.2020.28484