Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy
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Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
The Journal of infectious diseases
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 immunologicalresponse) 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 CD4were 4% (IQR, 1%–9%) and 13% (IQR, 8%–18%), respectively. In multivariable logistic regression, cases had lower age-associatedCD4+ T-cell count ratio (calculated as the ratio of the subject’s CD4+ T-cell count to the count expected in healthy individuals of thesame age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4+ and CD8+ T-cellcount ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profoundimmunosuppression; 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.
Description
Keywords
HIV, Africa, Children, Inflammation, Immunosuppression
Citation
Prendergast, A. J., Szubert, A. J., Berejena, C., Pimundu, G., Pala, P., Shonhai, A., ... & ARROW Trial Team. (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.DOI: 10.1093/infdis/jiw148