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Microbial translocation does not drive immune activation in Ugandan children with HIV

Fitzgerald, FC; Lhomme, E; Harris, K; Kenny, J; Doyle, R; Kityo, C; Shaw, LP; ... CHAPAS-3 Trial Team; + view all (2019) Microbial translocation does not drive immune activation in Ugandan children with HIV. Journal of Infectious Diseases , 219 (1) pp. 89-100. 10.1093/infdis/jiy495. Green open access

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Abstract

Objective: Immune activation is associated with morbidity/mortality in HIV-infection despite antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods: Nineteen markers of immune activation/inflammation were measured over 96 weeks in HIV-infected Ugandan children in CHAPAS-3 (ISRCTN69078957) and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques including next-generation sequencing. Results: Of 249 children included, 120 were HIV-infected ART-naïve and 22 ART-experienced (median (IQR) age 2.8(1.7-4.0) and 6.5(5.9-9.2) years; median baseline CD4% 20(14-24) and 35(31-39)). 107 were HIV-uninfected controls. Median (IQR) CD4% increase was 17(12-22) at week-96 in ART-naïve children, and viral load was<100 copies/mL in 76%/91% ART-naïve/experienced. Immune activation decreased with ART. Children could be divided by immune activation markers into clusters: cluster-1 (majority HIV-uninfected); cluster-2 (mixed HIV-uninfected/ART-naïve/ART-experienced); and cluster-3 (majority ART-naïve). Immune activation was low in cluster-1, decreased in cluster-3, and persisted in cluster-2. Blood microbial DNA levels were negative/very low across groups, with no difference between clusters except Enterobacteriaceae (higher in cluster-1,p<0.0001). Conclusion: Immune activation decreased with ART, with marker-clustering indicating different activation patterns by HIV/ART status. Levels of bacterial DNA in blood were low regardless of HIV/ART/immune activation status. Microbial translocation did not drive immune activation in this setting.

Type: Article
Title: Microbial translocation does not drive immune activation in Ugandan children with HIV
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/infdis/jiy495
Publisher version: http://doi.org/10.1093/infdis/jiy495
Language: English
Additional information: Copyright © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HIV, children, microbial translocation, immune activation, sequencing, pediatrics, Africa
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10063816
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