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Cessation of long-term cotrimoxazole prophylaxis in HIV-infected children does not alter the carriage of antimicrobial resistance genes

Francis, F; Gough, EK; Edens, TJ; Berejena, C; Bwakura-Dangarembizi, M; Shonhai, A; Nathoo, KJ; ... Manges, AR; + view all (2020) Cessation of long-term cotrimoxazole prophylaxis in HIV-infected children does not alter the carriage of antimicrobial resistance genes. JAIDS: Journal of Acquired Immune Deficiency Syndromes​ 10.1097/QAI.0000000000002489. (In press). Green open access

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Abstract

Background: Cotrimoxazole (CTX) is a broad-spectrum antimicrobial, combining trimethoprim and sulfamethoxazole. CTX prophylaxis reduces mortality and morbidity among people living with HIV in regions with high prevalence of bacterial infections and malaria. The Antiretroviral research for Watoto (ARROW) trial evaluated the effect of stopping versus continuing CTX prophylaxis in sub-Saharan Africa. / Methods: In this study, 72 HIV-infected Zimbabwean children, on antiretroviral therapy, provided fecal samples at 84- and 96-weeks after randomization to continue or stop CTX. DNA was extracted for whole metagenome shotgun sequencing, with sequencing reads mapped to the Comprehensive Antibiotic Resistance Database (CARD) to identify CTX and other antimicrobial resistance genes. / Results: There were minimal differences in the carriage of CTX resistance genes between groups. The dfrA1 gene, conferring trimethoprim resistance, was significantly higher in the continue group (p=0.039) and the tetA(P) gene conferring resistance to tetracycline was significantly higher in the stop group (p=0.013). CTX prophylaxis has a role in shaping the resistome, however stopping prophylaxis does not decrease resistance gene abundance. / Conclusion: No differences were observed in resistance gene carriage between the stop and continue groups. The previously shown multi-faceted protective effects of CTX in ARROW Trial clinical outcomes are not outweighed by the risk of multi-drug resistance gene selection due to prophylaxis. These findings are reassuring, given current recommendations for long-term CTX prophylaxis among children living with HIV in sub-Saharan Africa to decrease mortality and morbidity.

Type: Article
Title: Cessation of long-term cotrimoxazole prophylaxis in HIV-infected children does not alter the carriage of antimicrobial resistance genes
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAI.0000000000002489
Publisher version: https://doi.org/10.1097/QAI.0000000000002489
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10109631
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