Prendergast, Andrew J.Szubert, Alexander J.Berejena, ChipoPimundu, GodfreyPala, PietroShonhai, AnnieMusiime, VictorBwakura-Dangarembizi, MutsaPoulsom, HannahHunter, PatriciaMusoke, PhilippaKihembo, MacklynMunderi, PaulaGibb, Diana M.Spyer, MoiraWalker, A. SarahKlein, Nigel2021-12-152021-12-152016Prendergast, 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/jiw14810.1093/infdis/jiw148https://nru.uncst.go.ug/xmlui/handle/123456789/589Background. 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.enHIVAfricaChildrenInflammationImmunosuppressionArticle