. Dirajlal-Fargo S. 03/04/19; 258576; 814 Topic: Other
Dr. Sahera Dirajlal-Fargo
Dr. Sahera Dirajlal-Fargo
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Background: HIV-infection has become a chronic disease in pediatric patients with potential for long-term survival. The risk of cardiometabolic complications in HIV+ and exposed uninfected children (HEU) and their relationship to systemic inflammation is not well established. Our objective was to focus on how insulin resistance is associated with HIV related factors and markers of inflammation, immune activation and gut integrity.

Methods: This is a cross-sectional study in HIV+, HEU and HIV unexposed uninfected (HIV-) children aged 2-10 years old enrolled in Uganda. HIV+ children were on stable ART with HIV-1 RNA< 400 copies/mL. Participants were age, body mass index (BMI) and gender matched 1:1:1. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR). We measured markers of systemic inflammation, monocyte activation and gut integrity. Kruskal-Wallis tests were used to compare markers by HIV status, Pearson correlation and multiple linear regressions were used to assess associations of HOMA-IR with biomarkers.

Results: Overall, 172 participants were enrolled (57 HIV+, 59 HEU and 56 HIV-). Mean age was 7 years, 55% were females and mean BMI was 15. Among HIV+ children, mean CD4 was 34%, 93% had viral load ≤ 20 copies/mL, 77% were on a non-nucleotide reverse transcriptase regimen. Among traditional cardiovascular disease risk factors, HIV+ participants, compared to HEU and HIV- children, had higher waist hip ratio; HDL cholesterol, triglycerides and levels of HOMA-IR (figure). Four HIV+ participants had insulin resistance (HOMA> 2.5). sCD14, beta d glucan (a marker of fungal translocation) and zonulin (a marker of intestinal permeability) were also higher in the HIV+ group (p≤0.01). Factors associated with HOMA-IR included higher BMI, HDL (r≥0.09, p≤0.01), and lower sTNFRI (r=-0.19, p=0.02). HIV related factors were not associated with HOMA-IR (p≥0.08). After adjusting for age, gender, sTNFRI and family history of diabetes, BMI remained independently associated with HOMA-IR (β=0.14, p<0.01).

Conclusions: Despite viral suppression, HIV+ Ugandan children have disturbances in glucose metabolism, immune activation and gut integrity. However, higher BMI, and not immune activation, is associated with insulin resistance in this population. With obesity becoming more frequent in the HIV population, our findings support the need for preventive interventions aimed at weight control in the HIV population, including in children
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