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Inflammatory biomarkers in HIV-infected children hospitalized for severe malnutrition in Uganda and Zimbabwe

Prendergast, Andrew J.a,b; Berejena, Chipoc; Pimundu, Godfreyd; Shonhai, Anniec; Bwakura-Dangarembizi, Mutsac; Musiime, Victord,e; Szubert, Alexander J.a; Cook, Adrian D.a; Spyer, Moira J.a; Nahirya-Ntege, Patriciaf; Kekitiinwa, Adeodatag; Gibb, Diana M.a; Klein, Nigelh; Walker, A. Saraha

doi: 10.1097/QAD.0000000000002231

Objectives: A proportion of HIV-infected children with advanced disease develop severe malnutrition soon after antiretroviral therapy (ART) initiation. We tested the hypothesis that systemic inflammation underlies the pathogenesis of severe malnutrition in HIV-infected children.

Design: Cross-sectional laboratory substudy in 613 HIV-infected children initiating ART in Uganda and Zimbabwe.

Methods: We measured C-reactive protein (CRP), TNFα, IL-6 and soluble CD14 by ELISA in cryopreserved plasma at baseline (pre-ART) and week-4 (children with severe malnutrition only). Independent associations between baseline biomarkers and subsequent hospitalization for severe malnutrition were identified using multivariable fractional polynomial logistic regression.

Results: Compared with children without severe malnutrition (n = 574, median age 6.3 years, median baseline weight-for-age Z-score −2.2), children hospitalized for severe malnutrition post-ART (n = 39, median age 2.3 years, median baseline weight-for-age Z-score −4.8) had higher baseline CRP [median 13.5 (interquartile range 5.5, 41.1) versus 4.1 (1.4, 14.4) mg/l; P = 0.003] and IL-6 [median 9.2 (6.7, 15.6) versus 5.9 (4.6, 9.3) pg/ml; P < 0.0001], but similar overall TNFα, soluble CD14 and HIV viral load (all P > 0.06). In a multivariable model, higher pre-ART IL-6, lower TNFα and lower weight-for-age were independently associated with subsequent hospitalization for severe malnutrition. Between weeks 0 and 4, there was a significant rise in CRP, IL-6 and soluble CD14, and fall in TNFα and HIV viral load in children hospitalized for severe malnutrition (all P < 0.02).

Conclusion: Pre-ART IL-6 and TNFα were more strongly associated with hospitalization for severe malnutrition than CD4+ cell count or viral load, highlighting the importance of inflammation at the time of ART initiation in HIV-infected children.

aMRC Clinical Trials Unit at UCL

bBlizard Institute, Queen Mary University of London, London, UK

cUniversity of Zimbabwe, Harare, Zimbabwe

dJoint Clinical Research Centre

eCollege of Health Sciences, Makerere University, Kampala

fMRC/UVRI Uganda Research Unit on AIDS, Entebbe

gBaylor-Uganda, Mulago Hospital, Kampala, Uganda

hUCL Great Ormond Street Institute of Child Health, London, UK.

Correspondence to Prof. Andrew J. Prendergast, Blizard Institute, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK. Tel: +44 207 882 2269; fax: +44 207 882 2195; e-mail:

Received 26 August, 2018

Revised 22 November, 2018

Accepted 29 November, 2018

Copyright © 2019 Wolters Kluwer Health, Inc.