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Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV

Authors :
Fitzgerald, Felicity C
Lhomme, Edouard
Harris, Kathryn
Kenny, Julia
Doyle, Ronan
Kityo, Cissy
Shaw, Liam P
Abongomera, George
Musiime, Victor
Cook, Adrian
Brown, Julianne R
Brooks, Anthony
Owen-Powell, Ellen
Gibb, Diana M
Prendergast, Andrew J
Sarah Walker, A
Thiebaut, Rodolphe
Klein, Nigel
University College of London [London] (UCL)
Statistics In System biology and Translational Medicine (SISTM)
Inria Bordeaux - Sud-Ouest
Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH)
Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Bordeaux population health (BPH)
Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Great Ormond Street Hospital for Children [London] (GOSH)
Joint Clinical Research Centre
Queen Mary University of London (QMUL)
This work was supported by the Medical Research Council (MRC
grant MR/K023535/1 to F. F., grant MC_UU_12023/26 to the MRC Clinical Trials Unit at University College London [UCL], and support to CHAPAS-3), the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children National Health Service Foundation Trust (support to F. F.), UCL (support to F. F.), the Wellcome Trust (108065/Z/15/Z to A. J. P.), the European Developing Countries Clinical Trials Partnership (IP.2007.33011.006 to CHAPAS-3), the United Kingdom Department for International Development (support to CHAPAS-3), the Ministerio de Sanidady Consumo Spain (support to CHAPAS-3), and Cipla.
Source :
The Journal of Infectious Diseases, Journal of Infectious Diseases, Journal of Infectious Diseases, Oxford University Press (OUP), 2019, 219 (1), pp.89-100. ⟨10.1093/infdis/jiy495⟩, Journal of Infectious Diseases, 2019, 219 (1), pp.89-100. ⟨10.1093/infdis/jiy495⟩
Publication Year :
2018
Publisher :
Oxford University Press, 2018.

Abstract

Objective Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing. Results Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7–4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%–24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9–9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%–39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12–22 percentage points) at week 96 among ART-naive children, and the viral load was<br />We found no evidence of an association between microbial translocation and immune activation in Ugandan human immunodeficiency virus (HIV)–infected children over time during receipt of antiretroviral therapy or in comparison to HIV-uninfected controls. In this setting, other factors may be driving immune activation in both infected and uninfected children.

Details

Language :
English
ISSN :
15376613 and 00221899
Volume :
219
Issue :
1
Database :
OpenAIRE
Journal :
The Journal of Infectious Diseases
Accession number :
edsair.pmid.dedup....6baa47e4196a586ac58c6e0bb8855c3a