dc.contributor.author | Prendergast, AJ | |
dc.contributor.author | Szubert, AJ | |
dc.contributor.author | Berejena, C | |
dc.contributor.author | Pimundu, G | |
dc.contributor.author | Pala, P | |
dc.contributor.author | Shonhai, A | |
dc.contributor.author | Musiime, V | |
dc.contributor.author | Bwakura-Dangarembizi, M | |
dc.contributor.author | Poulsom, H | |
dc.contributor.author | Hunter, P | |
dc.contributor.author | Musoke, P | |
dc.contributor.author | Kihembo, M | |
dc.contributor.author | Munderi, P | |
dc.contributor.author | Gibb, DM | |
dc.contributor.author | Spyer, M | |
dc.contributor.author | Walker, AS | |
dc.contributor.author | Klein, N | |
dc.contributor.author | Team, ARROWT | |
dc.date.accessioned | 2019-02-27T13:23:27Z | |
dc.date.available | 2016-04-04 | |
dc.date.available | 2019-02-27T13:23:27Z | |
dc.date.issued | 2016-05-18 | |
dc.identifier.citation | Team, A. T., et al. (2016). "Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy." The Journal of Infectious Diseases 214(2): 226-236. | en_US |
dc.identifier.issn | 0022-1899 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/55587 | |
dc.description | This article has been accepted for publication in Journal of Infectious Disease. Published by Oxford University Press. | en_US |
dc.description.abstract | Background. Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)–infected children.
Methods. CD4+ T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART.
Results. There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4–11.4 years) and 5.8 years (IQR, 2.3–9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%–9%) and 13% (IQR, 8%–18%), respectively. In multivariable logistic regression, cases had lower age-associated CD4+ T-cell count ratio (calculated as the ratio of the subject's CD4+ T-cell count to the count expected in healthy individuals of the same age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4+ and CD8+ T-cell count ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profound immunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-α levels, and high age-associated CD8+ T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died).
Conclusions. While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes. | en_US |
dc.description.sponsorship | This work was supported by the Medical Research Council, the Department for International Development, the Wellcome Trust (grant 093768/Z/10/Z to A. J. P.), and ViiV Healthcare/GlaxoSmithKline (donation of drugs and funding of viral load assays). | en_US |
dc.format.extent | 226 - 236 | |
dc.language.iso | en | en_US |
dc.publisher | Oxford University Press | en_US |
dc.relation.ispartof | JOURNAL OF INFECTIOUS DISEASES | |
dc.rights | Creative Commons Attribution | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | HIV | en_US |
dc.subject | Africa | en_US |
dc.subject | children | en_US |
dc.subject | inflammation | en_US |
dc.subject | immunosuppression | en_US |
dc.title | Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy | en_US |
dc.type | Article | en_US |
dc.rights.holder | The Author 2016 | |
dc.identifier.doi | 10.1093/infdis/jiw148 | |
pubs.author-url | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000379822900010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a | en_US |
pubs.issue | 2 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 214 | en_US |
dcterms.dateAccepted | 2016-04-04 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |