Endothelial activation is associated with intestinal epithelial injury, systemic inflammation and treatment regimen in children living with vertically acquired HIV-1 infection

B Choudhury; J Brown; D G Ransy; J Brophy; F Kakkar; A Bitnun; L Samson; S Read; H Soudeyns; W Vaudry; S Houston; M T Hawkes

doi:10.1111/hiv.13012

Endothelial activation is associated with intestinal epithelial injury, systemic inflammation and treatment regimen in children living with vertically acquired HIV-1 infection

HIV Med. 2021 Apr;22(4):273-282. doi: 10.1111/hiv.13012. Epub 2020 Nov 5.

Authors

B Choudhury¹, J Brown², D G Ransy³, J Brophy^{4

5}, F Kakkar⁶, A Bitnun⁷, L Samson⁴, S Read⁷, H Soudeyns^{3

8}, W Vaudry¹, S Houston^{9

10}, M T Hawkes^{1

10

11

12

13}

Affiliations

¹ Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
² Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
³ Unité d'immunopathologie virale, Centre de recherche du CHU Sainte-Justine, Montréal, QC, Canada.
⁴ Division of Infectious Diseases, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
⁵ Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada.
⁷ Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
⁸ Department of Microbiology, Infectiology & Immunology, Université de Montréal, Montréal, QC, Canada.
⁹ Department of Medicine, Division of Infectious Diseases, University of Alberta, Edmonton, AB, Canada.
¹⁰ School of Public Health, University of Alberta, Edmonton, AB, Canada.
¹¹ Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
¹² Stollery Science Lab, Edmonton, AB, Canada.
¹³ Women and Children's Health Research Institute, Edmonton, AB, Canada.

PMID: 33151601
DOI: 10.1111/hiv.13012

Abstract

Background: Premature development of cardiovascular disease in children living with HIV-1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH.

Methods: This was a cross-sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation-Canadian Child Cure Cohort (EPIC⁴ ) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury [intestinal fatty acid binding protein-1 (IFABP)], systemic inflammation [tumour necrosis factor (TNF) and interleukin-6 (IL-6)] and endothelial activation [angiopoietin-2 (Ang2), soluble vascular endothelial growth factor-1 (sVEGFR1) and soluble endoglin (sEng)] were quantified by enzyme-linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways.

Results: Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P < 0.001 for all correlations). An endothelial activation index, derived by factor analysis of the three endothelial biomarkers, was correlated with TNF (ρ = 0.47, P < 0.001), IL-6 (ρ = 0.60, P < 0.001) and intestinal fatty acid binding protein-1 (ρ = 0.67, P < 0.001). Current or past treatment with ritonavir-boosted lopinavir (LPV/r) was associated with endothelial activation (odds ratio = 5.0, 95% CI: 1.7-17, P = 0.0020).

Conclusions: Endothelial activation is prevalent in CLWH despite viral suppression with combination ART and is associated with intestinal epithelial injury, systemic inflammation and treatment with LPV/r.

Keywords: HIV; child; endothelium; inflammation; intestinal epithelial injury; microbial translocation.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Canada
Child
Cross-Sectional Studies
HIV Infections* / complications
HIV-1*
Humans
Inflammation
Vascular Endothelial Growth Factor A

Substances

Biomarkers
Vascular Endothelial Growth Factor A

Grants and funding

CIHR/Canada