Effect of Once-Weekly Azithromycin vs Placebo in Children With HIV-Associated Chronic Lung Disease: The BREATHE Randomized Clinical Trial

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 may be effective in treating HCLD through reduc...

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Bibliographic Details
Published in:JAMA network open 2020-12, Vol.3 (12), p.e2028484
Main Authors: Ferrand, Rashida A, McHugh, Grace, Rehman, Andrea M, Mujuru, Hilda, Simms, Victoria, Majonga, Edith D, Nicol, Mark P, Flaegstad, Trond, Gutteberg, Tore J, Gonzalez-Martinez, Carmen, Corbett, Elizabeth L, Rowland-Jones, Sarah L, Kranzer, Katharina, Weiss, Helen A, Odland, Jon O
Format: Article
Language:English
Subjects:
Adolescent
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - adverse effects
Antibiotics
Azithromycin - administration & dosage
Azithromycin - adverse effects
Basale medisinske, odontologiske og veterinærmedisinske fag: 710
Basic medical, dental and veterinary science disciplines: 710
Clinical trials
Double-Blind Method
Drug Dosage Calculations
Female
HIV Infections - complications
Hospitalization - statistics & numerical data
Humans
Lung diseases
Male
Medical disciplines: 700
Medisinske Fag: 700
Online Only
Original Investigation
Pulmonary Disease, Chronic Obstructive - drug therapy
Pulmonary Disease, Chronic Obstructive - etiology
Pulmonary Disease, Chronic Obstructive - physiopathology
Pulmonary Medicine
Respiratory Tract Infections - drug therapy
Respiratory Tract Infections - immunology
Treatment Outcome
VDP
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Summary: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 may be effective in treating HCLD through reducing respiratory tract infections and inflammation. To determine whether prophylactic azithromycin is effective in preventing worsening of lung function and in reducing acute respiratory exacerbations (AREs) in children with HCLD taking ART. This double-blind, placebo-controlled, randomized clinical trial (BREATHE) was conducted between 2016 and 2019, including 12 months of follow-up, at outpatient HIV clinics in 2 public sector hospitals in Malawi and Zimbabwe. Participants were randomized 1:1 to intervention or placebo, and participants and study personnel were blinded to treatment allocation. Participants included children aged 6 to 19 years with perinatally acquired HIV and HCLD (defined as forced expiratory volume in 1 second [FEV1] z score < -1) who were taking ART for 6 months or longer. Data analysis was performed from September 2019 to April 2020. Once-weekly oral azithromycin with weight-based dosing, for 48 weeks. All outcomes were prespecified. The primary outcome was the mean difference in FEV1 z score using intention-to-treat analysis for participants seen at end line. Secondary outcomes included AREs, all-cause hospitalizations, mortality, and weight-for-age z score. A total of 347 individuals (median [interquartile range] age, 15.3 [12.7-17.7] years; 177 boys [51.0%]) were randomized, 174 to the azithromycin group and 173 to the placebo group; 162 participants in the azithromycin group and 146 placebo group participants had a primary outcome available and were analyzed. The mean difference in FEV1 z score was 0.06 (95% CI, -0.10 to 0.21; P = .48) higher in the azithromycin group than in the placebo group, a nonsignificant difference. The rate of AREs was 12.1 events per 100 person-years in the azithromycin group and 24.7 events per 100 person-years in the placebo groups (hazard ratio, 0.50; 95% CI, 0.27 to 0.93; P = .03). The hospitalization rate was 1.3 events per 100 person-years in the azithromycin group and 7.1 events per 100 person-years in the placebo groups, but the difference was not significant (hazard ratio, 0.24; 95% CI, 0.06 to 1.07; P = .06). Three deaths occurred, all in the placebo group. The mean weight-for-age z score was 0.03 (
ISSN:2574-3805
2574-3805
DOI:10.1001/jamanetworkopen.2020.28484