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Effect of azithromycin on incidence of acute respiratory exacerbations in children with HIV taking antiretroviral therapy and co-morbid chronic lung disease: a secondary analysis of the BREATHE trial

Price, Amy, McHugh, Grace, Simms, Victoria, Semphere, Robina, Ngwira, Lucky-Gift, Bandason, Tsitsi, Mujuru, Hilda, Odland, Jon O, Ferrand, Rashida A and Rehman, Andrea M (2021) 'Effect of azithromycin on incidence of acute respiratory exacerbations in children with HIV taking antiretroviral therapy and co-morbid chronic lung disease: a secondary analysis of the BREATHE trial'. EClinicalMedicine, Vol 42, Issue 101195.

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Abstract

Background: In 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.
Methods: The 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.
Findings: We analysed data from 345 participants (171 allocated to azithromycin and 174 allocated to placebo). In the placebo arm, the rate of AREs were higher among those with an abnormally high respiratory rate at baseline (adjusted rate ratio (aRR) 2.90 95% CI 1.30-6.46 p-value 0.0068) and among those with a CD4 cell count <200 cells/mm3 (aRR 2.50; 95%CI 1.04-5.97; p-value 0.0387). We found some evidence for heterogeneity in the effect of azithromycin by sex (p-value for interaction=0.0660); males had a greater reduction in the rate of ARE with azithromycin treatment compared to females. There was weak evidence of azithromycin having 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.
Interpretation: These may represent subgroups who may benefit the most from treatment with weekly azithromycin
Funding: Global Health and Vaccination Programme of the Norwegian Research Council.

Item Type: Article
Subjects: WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.2 Therapy
WF Respiratory System > Lungs > WF 600 Lungs
WS Pediatrics > Diseases of Children and Adolescents > By System > WS 280 Respiratory system
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.eclinm.2021.101195
Depositing User: Debbie Jenkins
Date Deposited: 04 Jan 2022 13:52
Last Modified: 04 Jan 2022 13:52
URI: https://archive.lstmed.ac.uk/id/eprint/19670

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