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AZITHROMYCIN FOR TREATMENT OF HIV-RELATED CHRONIC LUNG DISEASE IN AFRICAN CHILDREN
Rashida A. Ferrand1, Grace McHugh2, Andrea M. Rehman1, Hilda Mujuru3, Mark Nicol4, Sarah Rowland-Jones5, Trond Flaegstad6, Tore Gurtteberg6, Victoria Simms1
1London School of Hygiene & Tropical Medicine, London, UK,2Biomedical Research and Training Institute, Harare, Zimbabwe,3University of Zimbabwe, Harare, Zimbabwe,4University of Cape Town, Cape Town, South Africa,5University of Oxford, Oxford, UK,6Arctic University of Norway, Tromso, Norway
HIV-related chronic lung disease (HCLD) in children and adolescents is associated with substantial morbidity, despite antiretroviral therapy (ART). HCLD may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesized that azithromycin (AZM) would improve lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation.
We conducted a randomized double-blinded, placebo-controlled trial among children aged 6-19 years on ART with HCLD (defined as FEV1 Z-score<-1) in Malawi and Zimbabwe. Once-weekly AZM (with weight-based dosing) or placebo was administered for 48 weeks. Primary outcome was mean difference in FEV1 Z-score. Secondary outcomes were mortality, hospitalisations and acute respiratory exacerbations (ARE). Outcomes were adjusted for age, sex, trial site and HIV viral load (VL) at baseline, using robust standards errors for multiple event data.
A total of 347 children were recruited (49% female, median age 15.3 years) of whom 44% had a VL>1000copies/ml and 74% were on first-line ART; 90% were taking cotrimoxazole prophylaxis and the median CD4 count was 571cells/l. Previous treatment for tuberculosis was reported by 28% and chronic cough by 9%, and 44% had an abnormally high respiratory rate. We randomized 174 to AZM and 173 to placebo. At the end of 48 weeks of treatment, the mean difference between arms in FEV1 Z-score was 0.06 (95% CI 0.10, 0.21; p=0.48). There was a significant difference in incidence of ARE, adjusted incidence rate ratio 0.50 (95% CI 0.25, 1.00; p=0.05) (Figure 1). The rate ratio for hospitalizations was 0.24 (0.06-1.07, p=0.061) comparing AZM to placebo. Mortality was 0/100pyrs in the AZM vs 1.95/100pyrs in the placebo arm.
This is the first ever trial of an intervention to address HCLD in children. While once-weekly AZM had no effect on pulmonary function, it reduced mortality, hospitalizations and incidence of AREs. AZM is an effective intervention in reducing morbidity associated with HCLD in children and adolescents.