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4 results on '"Kihembo, Macklyn"'

2. The impact of viraemia on inflammatory biomarkers and CD4 cell subpopulations in HIV-infected children in sub-Saharan Africa

Author

Prendergast, Andrew J., primary, Szubert, Alexander J., additional, Pimundu, Godfrey, additional, Berejena, Chipo, additional, Pala, Pietro, additional, Shonhai, Annie, additional, Hunter, Patricia, additional, Arrigoni, Francesca I.F., additional, Musiime, Victor, additional, Bwakura-Dangarembizi, Mutsa, additional, Musoke, Philippa, additional, Poulsom, Hannah, additional, Kihembo, Macklyn, additional, Munderi, Paula, additional, Gibb, Diana M., additional, Spyer, Moira J., additional, Walker, A. Sarah, additional, and Klein, Nigel, additional

Published
2021
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3. Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy

Author

Prendergast, Andrew J, Szubert, Alexander J, Berejena, Chipo, Pimundu, Godfrey, Pala, Pietro, Shonhai, Annie, Musiime, Victor, Bwakura-Dangarembizi, Mutsa, Poulsom, Hannah, Hunter, Patricia, Musoke, Philippa, Kihembo, Macklyn, Munderi, Paula, Gibb, Diana M, Spyer, Moira, Walker, A Sarah, Klein, Nigel, and ARROW Trial Team

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.

Published
2016

4. Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy.

Author

Prendergast AJ, Szubert AJ, Berejena C, Pimundu G, Pala P, Shonhai A, Musiime V, Bwakura-Dangarembizi M, Poulsom H, Hunter P, Musoke P, Kihembo M, Munderi P, Gibb DM, Spyer M, Walker AS, and Klein N

Subjects
Africa, C-Reactive Protein analysis, CD4 Lymphocyte Count, Child, Child, Preschool, Female, HIV isolation & purification, HIV Infections mortality, Humans, Interleukin-6 blood, Lipopolysaccharide Receptors blood, Longitudinal Studies, Male, Survival Analysis, Tumor Necrosis Factor-alpha blood, Viral Load, Anti-Retroviral Agents therapeutic use, Biomarkers blood, HIV Infections drug therapy, HIV Infections pathology, Inflammation pathology
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., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Published
2016
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