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Subclinical Vascular Disease in Children With Human Immunodeficiency Virus in Uganda Is Associated With Intestinal
Sahera Dirajlal-Fargo1,2,3, Zainab Albar3, Emily Bowman4
1University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Insights
Children with perinatally acquired HIV (PHIV) in Africa show early cardiovascular disease (CVD) risk and vascular changes. Gut barrier dysfunction may contribute to these subclinical vascular issues despite viral suppression.
Area of Science:
- Pediatrics
- Cardiology
- Infectious Diseases
Background:
- Cardiovascular disease (CVD) risk and mechanisms in children with perinatally acquired HIV (PHIV) in sub-Saharan Africa are understudied.
- PHIV are at risk for long-term health complications, including CVD.
Purpose of the Study:
- To investigate CVD risk factors and subclinical vascular changes in children living with PHIV in sub-Saharan Africa.
- To explore the association between markers of inflammation, immune activation, and gut integrity with vascular changes in PHIV.
Main Methods:
- Evaluated common carotid artery intima-media thickness (IMT) and pulse-wave velocity (PWV) in 101 PHIV and 96 HIV-negative children.
- Measured plasma and cellular markers of monocyte activation, T-cell activation, oxidized lipids, and gut integrity (zonulin).
- PHIV children were on antiretroviral therapy (ART) with suppressed HIV-1 RNA levels.
Main Results:
- PHIV children exhibited higher waist-hip ratio, triglycerides, and insulin resistance compared to HIV-negative children.
- Median IMT was slightly increased in PHIV children, indicating early structural vascular changes.
- Higher levels of intestinal permeability (zonulin) were significantly associated with increased IMT in PHIV, even after adjustments.
Conclusions:
- African children with PHIV demonstrate evidence of CVD risk and structural vascular changes, even with viral suppression.
- Intestinal barrier dysfunction may play a role in the development of subclinical vascular disease in this population.
- Further research is needed to understand and mitigate CVD risk in PHIV.
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.
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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