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.


Journal

EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727

Informations de publication

Date de publication:
Dec 2021
Historique:
received: 22 06 2021
revised: 23 10 2021
accepted: 25 10 2021
entrez: 25 11 2021
pubmed: 26 11 2021
medline: 26 11 2021
Statut: epublish

Résumé

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. 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. Participants were recruited from Zimbabwe and Malawi between15 June 2016 and 4 September 2018. We analysed data from 345 participants (171 allocated to azithromycin and 174 allocated to placebo). Rates of AREs were higher among those with an abnormally high respiratory rate at baseline (adjusted rate ratio (aRR) 2.08 95% CI 1.10-3.95 p-value 0.02) and among those with a CD4 cell count <200 cells/mm These may represent subgroups who may benefit the most from treatment with weekly azithromycin, which could help guide targeted treatment. There was no funding source for this post hoc analysis.

Sections du résumé

BACKGROUND 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 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. Participants were recruited from Zimbabwe and Malawi between15 June 2016 and 4 September 2018.
FINDINGS RESULTS
We analysed data from 345 participants (171 allocated to azithromycin and 174 allocated to placebo). Rates of AREs were higher among those with an abnormally high respiratory rate at baseline (adjusted rate ratio (aRR) 2.08 95% CI 1.10-3.95 p-value 0.02) and among those with a CD4 cell count <200 cells/mm
INTERPRETATION CONCLUSIONS
These may represent subgroups who may benefit the most from treatment with weekly azithromycin, which could help guide targeted treatment.
FUNDING BACKGROUND
There was no funding source for this post hoc analysis.

Identifiants

pubmed: 34820609
doi: 10.1016/j.eclinm.2021.101195
pii: S2589-5370(21)00476-4
pmc: PMC8599092
doi:

Types de publication

Journal Article

Langues

eng

Pagination

101195

Subventions

Organisme : Medical Research Council
ID : MR/R010161/1
Pays : United Kingdom

Informations de copyright

© 2021 The Author(s).

Déclaration de conflit d'intérêts

Dr Ferrand is funded by the Wellcome Trust. Drs Rehman, and Simms are partly funded by grant MR/R010161/1 from the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. The remaining authors declare no conflict of interest.

Références

Infection. 2017 Dec;45(6):801-809
pubmed: 28660356
Public Health Nutr. 2001 Jun;4(3):757-64
pubmed: 11415482
Clin Infect Dis. 2018 Jan 6;66(2):274-281
pubmed: 29020237
Lancet Respir Med. 2013 Oct;1(8):610-620
pubmed: 24461664
Chest. 2010 Jul;138(1):158-64
pubmed: 20173055
J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):275-281
pubmed: 27171738
S Afr Med J. 2018 Dec 13;109(1):27-34
pubmed: 30606301
Trials. 2017 Dec 28;18(1):622
pubmed: 29282143
Ann Am Thorac Soc. 2017 May;14(5):722-729
pubmed: 28248548
BMC Infect Dis. 2021 Feb 25;21(1):216
pubmed: 33632144
N Engl J Med. 2007 Nov 22;357(21):2189-94
pubmed: 18032770
Clin Infect Dis. 2003 May 15;36(10):e127-30
pubmed: 12746792
PLoS Med. 2012 Feb;9(2):e1001167
pubmed: 22346735
S Afr Med J. 1999 Oct;89(10):1079-84
pubmed: 10582064
Trop Med Int Health. 2018 Feb;23(2):149-155
pubmed: 29160948
PLoS Med. 2017 Nov 7;14(11):e1002407
pubmed: 29112692
Clin Infect Dis. 2020 Jan 16;70(3):483-490
pubmed: 30938406
AIDS. 2016 Nov 28;30(18):2795-2803
pubmed: 27662546
Lancet. 2011 Mar 19;377(9770):1011-8
pubmed: 21411136
JAMA Netw Open. 2020 Dec 1;3(12):e2028484
pubmed: 33331916
Arch Dis Child. 1995 Jul;73(1):25-9
pubmed: 7639544
Pediatr Pulmonol. 2011 Apr;46(4):393-400
pubmed: 20967845
Chest. 2002 Jan;121(1):64-72
pubmed: 11796433
Perspect Clin Res. 2016 Apr-Jun;7(2):106-7
pubmed: 27141478

Auteurs

Amy Price (A)

Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.

Grace McHugh (G)

Biomedical Research and Training Institute, Harare, Zimbabwe.

Victoria Simms (V)

Biomedical Research and Training Institute, Harare, Zimbabwe.
MRC International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

Robina Semphere (R)

Department of Microbiology & HNTI, College of Medicine, Blantyre, Malawi.

Lucky G Ngwira (LG)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.

Tsitsi Bandason (T)

Biomedical Research and Training Institute, Harare, Zimbabwe.

Hilda Mujuru (H)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Jon O Odland (JO)

Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.

Rashida A Ferrand (RA)

Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
Biomedical Research and Training Institute, Harare, Zimbabwe.

Andrea M Rehman (AM)

MRC International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

Classifications MeSH