Azithromycin reduces exacerbations in children with HIV-associated chronic lung disease
Children with HIV-associated chronic lung diseases acute respiratory exacerbations .
“As well as being safe and well-tolerated, the pharmacokinetics of [azithromycin] are unique, with high intracellular uptake and slow hepatic excretion,” Rashida A. Ferrand, PhD, senior lecturer in the department of clinical research at the London School of Hygiene and Tropical Medicine, London, and colleagues wrote. “The resulting high tissue concentrations made once-weekly dosing feasible, possibly reducing nonadherence.”
The double-blind, placebo-controlled, randomized clinical trial (median age, 15.3 years; 51% ) with perinatally acquired HIV and HIV-associated chronic lung disease who were taking antiretroviral therapy for 6 months or longer. articipants to once-weekly oral azithromycin (n = 174) or placebo (n = 173) for 48 weeks.
The primary outcome was mean difference in FEV1 z score using intention-to-treat analysis. Secondary outcomes included acute respiratory exacerbations, all-cause hospitalizations, mortality and weight-for-age z score.
A total of 162 participants in the azithromycin group and 146 participants in the placebo group had primary outcome data available with a nonsignificant in FEV1 z score of 0.06 (95% CI, –0.1-0.21; P = .48).
Acute respiratory exacerbation rates were 12.1 events per 100 person-years in the azithromycin group compared with 24.7 events per 100 person-years in the placebo group (HR = 0.5; 95% CI, 0.27-0.93; P = .03). ospitalization rates were not significant with 1.3 events for the azithromycin group and 7.1 events in the placebo group (HR = 0.24; 95% CI, 0.06-1.07; P= .56). ean weight-for-age z score not significant with a 0.03 (95% CI, –0.08-0.14; P = .56) higher score in the azithromycin group than the placebo group.
Researchers observed 3 deaths in the placebo group and deaths in the azithromycin group. There were no drug-related severe adverse events.
According to the researchers, azithromycin treatment antimicrobial resistance in the airway microbiome, which increase macrolide azithromycin resistance in bystander organisms.
“These concerns justify the need for a selective approach to treatment. Future trials should investigate [azithromycin] therapeutic effects against such factors as disease severity and pattern, functional impairment and exten of immunocompromise to identify patients who would gain most from such an intervention,” the researchers wrote. “Future research should identify patient groups who would benefit most from this intervention, optimum treatment length and dosing schedules and sustainability of treatment effect.”