Ambient air pollution is associated with vascular disease in Ugandan HIV-positive adolescents.

OBJECTIVE: In this study, we aim to investigate the relationship between particulate matter, a common proxy indicator for air pollution, and markers of inflammation, monocyte activation, and subclinical vascular disease. DESIGN: A cross-sectional study. METHODS: Adolescents with perinatally acquired HIV (PHIV) and HIV-uninfected adolescents between 10 and 18years living near Kampala, Uganda were included. Daily ambient concentrations of particulate matter (PM2.5) were measured from the Eastern Arica GEOHealth Hub. Outcome variables measured were carotid intima-media thickness (IMT), as well as plasma markers of systemic inflammation, oxidized lipids, and gut integrity. Multivariable quantile regression models were used to explore the relationship between PM2.5 and IMT. RESULTS: One hundred and nineteen participants (69 PHIV, 50 HIV-uninfected) were included. The median (Q1, Q3) age was 12.7 (11.4,14.2) years, 55% were girls. Median daily PM2.5 exposure was 29.08 µg/m3 (23.40, 41.70). There was no significant difference in exposure of PM2.5 between groups (P  = 0.073). PM2.5 significantly correlated with intestinal permeability (zonulin; r = 0.43, P < 0.001), monocyte activation (soluble CD163: r  = 0.25, P = 0.053), and IMT (r  = 0.35, P = 0.004) in PHIV but not in HIV-uninfected (P ≥ 0.05). In multivariable quantile regression, after adjusting for age, sex, poverty level, soluble CD163, and zonulin, daily PM2.5 concentrations remained associated with IMT [ß  = 0.005, 95% CI (0.0003-0.010), P = 0.037] in adolescents with PHIV. CONCLUSION: Adolescents in urban Uganda are exposed to high levels of air pollution. Both PM2.5 and HIV have independently been observed to contribute to atherosclerotic disease, and our findings suggest the combined effects of HIV and air pollution may amplify the development of cardiovascular disease.

Increased monocyte and T-cell activation in treated HIV+ Ugandan children: associations with gut alteration and HIV factors.

INTRODUCTION: The pathophysiology of immune activation and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied. METHODS: We enrolled 101 children living with PHIV and 96 HIV-negative controls (HIV-). All participants were between 10 and 18 years of age with no known active infections. PHIVs were on ART with HIV-1 RNA level 400 copies/ml or less. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4 and CD8), oxidized lipids, markers of gut integrity and fungal translocation. Spearman correlations and linear regression models were used. RESULTS: Overall median (Q1; Q3) age was 13 years (11; 15) and 52% were girls. Groups were similar by age, sex and BMI. Median ART duration was 10 years (8; 11). PHIVs had higher monocyte and T-cell activation; higher sCD14 (P = 0.01) and elevated frequencies of nonclassical monocytes (P < 0.001 for both). Markers of systemic inflammation (hsCRP), fungal translocation (BDG), intestinal permeability (zonulin) and oxidized lipids (ox LDL) correlated with monocyte and T-cell activation in PHIV (≤0.05). After adjusting for age, sex, ART duration, protease inhibitor and nonnucleoside reverse transcriptase inhibitor use, a modest association between BDG and activated CD4 T cells was observed (ß=0.65, P < 0.01). Oxidized LDL was inversely associated with activated T cells, inflammatory and nonclassical monocytes (P < 0.01). CONCLUSION: Ugandan children with perinatally acquired HIV with viral suppression have evidence of ongoing immune activation. Intestinal barrier dysfunction and fungal translocation may be involved in chronic immune dysfunction.

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

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 (ß = 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.