Prendergast, A;
Szubert, A;
Berejena, C;
Pimundu, G;
Pala, P;
Shonhai, A;
Musiime, V;
... Klein, N; + view all
(2016)
Baseline inflammatory biomarkers identify subgroups of HIV-infected African children with differing responses to antiretroviral therapy.
Journal of Infectious Diseases
, 214
(2)
pp. 226-236.
10.1093/infdis/jiw148.
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Abstract
Background: Identifying determinants of morbidity and mortality may help target future interventions for HIV-infected children. / Methods: CD4, HIV-1 viral load (VL) and biomarkers (CRP/TNF-α/IL-6/sCD14/IL-7) were measured at ART initiation in the ARROW trial (case-cohort design). Cases were deaths, new/recurrent WHO-4 events or immunological non-responders. / Results: There were 115 cases (54 deaths, 45 WHO-4 events, 49 immunological non-responders) and 485 controls. Pre-ART, median(IQR) age of cases vs controls was 8.2(4.4-11.4) vs 5.8(2.3-9.3) and CD4% 4%(1-9)vs 13%(8-18). In multivariable logistic regression, cases had lower CD4-for-age (p<0.0001) and higher IL-6 (p=0.002). Clustering biomarkers and CD4-/CD8-for-age identified 4 groups of children: Group-1 had the most cases (41%; 16% died) and profound immunosuppression; Group-2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression, high inflammatory biomarkers and VL; Group-3 comprised young children with moderate immunosuppression, high TNF-α and CD8-for-age but lower event rates (12% cases; 7% died); Group-4 comprised older children with low inflammatory biomarkers, lower VL and good clinical outcomes (11% cases; 5% died). / Conclusions: While immunosuppression is the major determinant of poor outcome on ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Anti-inflammatory interventions may help improve outcomes.
| Type: | Article |
|---|---|
| Title: | Baseline inflammatory biomarkers identify subgroups of HIV-infected African children with differing responses to antiretroviral therapy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/infdis/jiw148 |
| Publisher version: | http://doi.org/10.1093/infdis/jiw148 |
| Language: | English |
| Additional information: | © The Author 2016. 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. DOI: 10.1093/infdis/jiw148 |
| Keywords: | HIV; Africa; children; inflammation; immunosuppression |
| 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 > 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/1477539 |
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