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Current HIV Research

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ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

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Systematic Review Article

Biomarkers of Growth Faltering and Neurodevelopmental Delay in Children who are HIV-Exposed but Uninfected: A Systematic Review

Author(s): Reshma Sirajee, Jason Brophy, Andrea L. Conroy, Sophie Namasopo, Robert O. Opoka, Urvi Rai, Sarah Forgie, Bukola O. Salami and Michael T. Hawkes*

Volume 21, Issue 3, 2023

Published on: 20 July, 2023

Page: [172 - 184] Pages: 13

DOI: 10.2174/1570162X21666230505152846

Price: $65

Abstract

Introduction: Children who are HIV-exposed but uninfected (CHEU) are at risk of linear growth faltering and neurodevelopmental delay. Circulating biomarkers associated with these adverse outcomes may elucidate pathways of injury.

Objective: To identify biomarkers associated with growth faltering and neurodevelopmental delay in CHEU.

Methods: We performed a systematic review of electronic databases MEDLINE (1946-April 2021), EMBASE (1974-April 2021), Scopus (2004-April 2021), and PubMed (1985-April 2021), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42021238363).

Results: We found seven studies associating biomarker abnormalities and growth outcomes in CHEUs and two studies on biomarker abnormalities and neurodevelopmental delay. Biomarker abnormalities associated with growth restriction were: C-reactive protein (CRP), tumour necrosis factor (TNF), interferon-gamma (IFN-γ), interleukin (IL)-12p70, IFN-γ-induced protein-10 (CXCL10/IP-10), lipopolysaccharide binding protein (LBP), insulin-like growth factor-1 (IGF-1), and IGF-binding protein-1 (IGFBP-1). Biomarkers associated with motor, language, and cognitive delay were CRP, IFN-γ, IL-1β, -2, -4, -6, -10, -12p70, neutrophil gelatinase-associated lipocalin (NGAL), granulocyte-macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase- 9 (MMP-9).

Conclusion: Elevated markers of inflammation (acute phase reactants, pro-inflammatory cytokines, chemokines) and intestinal microbial translocation are associated with growth faltering. Elevated markers of inflammation are associated with adverse neurodevelopment.

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Graphical Abstract

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