TY - JOUR
T1 - Monocyte activation and gut barrier dysfunction in South African youth on antiretroviral therapy and their associations with endothelial dysfunction
AU - Dirajlal-Fargo, Sahera
AU - Yu, Jiao
AU - Albar, Zainab
AU - Sattar, Abdus
AU - Mahtab, Sana
AU - Jao, Jennifer
AU - Myer, Landon
AU - Zar, Heather J.
AU - McComsey, Grace A.
N1 - Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - gut integrity
KW - inflammation
KW - monocyte activation
KW - pediatric HIV
KW - translocation
KW - vascular function
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U2 - 10.1097/QAD.0000000000002615
DO - 10.1097/QAD.0000000000002615
M3 - Article
C2 - 32769763
AN - SCOPUS:85089301824
SN - 0269-9370
VL - 34
SP - 1615
EP - 1623
JO - AIDS
JF - AIDS
IS - 11
ER -