Subclinical Vascular Disease in Children With Human Immunodeficiency Virus in Uganda Is Associated With Intestinal Barrier Dysfunction

乌干达人类免疫缺陷病毒感染儿童的亚临床血管疾病与肠道屏障功能障碍有关

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作者:Sahera Dirajlal-Fargo, Zainab Albar, Emily Bowman, Danielle Labbato, Abdus Sattar, Christine Karungi, Chris T Longenecker, Rashida Nazzinda, Nicholas Funderburg, Cissy Kityo, Victor Musiime, Grace A McComsey

Background

The risk of cardiovascular disease (CVD) and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied.

Conclusions

Our study shows that African PHIV have evidence of CVD risk and structural vascular changes despite viral suppression. Intestinal intestinal barrier dysfunction may be involved in the pathogenesis of subclinical vascular disease in this population.

Methods

Mean common carotid artery intima-media thickness (IMT) and pulse-wave velocity (PWV) were evaluated in 101 PHIV and 96 HIV-negative (HIV-) children. PHIV were on ART, with HIV-1 RNA levels ≤400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation, oxidized lipids, and gut integrity.

Results

Overall median (interquartile range, Q1-Q3) age was 13 (11-15) years and 52% were females. Groups were similar by age, sex, and BMI. Median ART duration was 10 (8-11) years. PHIV had higher waist-hip ratio, triglycerides, and insulin resistance (P ≤ .03). Median IMT was slightly thicker in PHIVs than HIV- children (1.05 vs 1.02 mm for mean IMT and 1.25 vs 1.21 mm for max IMT; P < .05), while PWV did not differ between groups (P = .06). In univariate analyses, lower BMI and oxidized LDL, and higher waist-hip ratio, hsCRP, and zonulin correlated with thicker IMT in PHIV (P ≤ .05). After adjustment for age, BMI, sex, CD4 cell count, triglycerides, and separately adding sCD163, sCD14, and hsCRP, higher levels of intestinal permeability as measured by zonulin remained associated with IMT (β = 0.03 and 0.02, respectively; P ≤ .03). Conclusions: Our study shows that African PHIV have evidence of CVD risk and structural vascular changes despite viral suppression. Intestinal intestinal barrier dysfunction may be involved in the pathogenesis of subclinical vascular disease in this population.

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