Monocyte activation and gut barrier dysfunction in South African youth on antiretroviral therapy and their associations with endothelial dysfunction

Sahera Dirajlal-Fargo, Jiao Yu, Zainab Albar, Abdus Sattar, Sana Mahtab, Jennifer Jao, Landon Myer, Heather J. Zar, Grace A. McComsey

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background:There is evidence for endothelial dysfunction in youth living with perinatally acquired HIV (YLPHIV). However, little data exist on its mechanisms.Methods:YLPHIV and age-matched HIV-uninfected (HIV-) youth enrolled in the Cape Town Adolescent Antiretroviral Cohort in South Africa between 9 and 14 years of age were included. YLPHIV were on antiretroviral therapy more than 6 months with viral load less than 400 copies/ml at baseline and 24 months. Serum biomarkers of systemic inflammation, monocyte activation, intestinal integrity, and oxidized LDL-cholesterol were measured at baseline and after 24 months. Endothelial function was measured at 24 months using reactive hyperemic index (RHI); endothelial dysfunction was defined as RHI less than 1.35. Spearman correlation coefficient and quantile regression were used to examine associations between RHI and different biomarkers.Results:We included 266 YLPHIV and 69 HIV- participants. At baseline, median (Q1, Q3) age was 12 (11, 13) years and 53% were females. YLPHIV had poorer endothelial function compared with HIV- youth (RHI = 1.36 vs. 1.52, P < 0.01). At baseline and 24 months, YLPHIV had higher markers of monocyte activation (soluble CD14), gut barrier dysfunction (intestinal fatty acid binding protein) and oxidized LDL-cholesterol (P ≤ 0.04) compared with HIV- youth. Among YLPHIV, soluble CD14 remained associated with endothelial dysfunction after adjusting for age, sex, Tanner stage, and antiretroviral therapy duration (β: -0.05, P = 0.01).Conclusion:Despite viral suppression, South African YLPHIV have poor endothelial function and persistent evidence of monocyte activation and gut barrier dysfunction compared with HIV- youth. The long-term clinical significance of gut integrity and monocyte activation needs to be further assessed in YLPHIV.

Original languageEnglish (US)
Pages (from-to)1615-1623
Number of pages9
JournalAIDS
Volume34
Issue number11
DOIs
StatePublished - Sep 1 2020

Keywords

  • gut integrity
  • inflammation
  • monocyte activation
  • pediatric HIV
  • translocation
  • vascular function

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

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