680-T.

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Glucose Homeostasis, Serum Lipids, and Abdominal Adipose Tissue Distribution in Protease Inhibitor (PI)-Treated and Naïve HIV-Infected Children
A. Bitnun*, E. Sochett, P. Babyn, C. Arneson, S. Holowka, S. Read, and S. King
Hosp. for Sick Children, Univ. of Toronto, ON, Canada
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Background: The purpose of this study is to determine the extent and severity of abnormalities of glucose homeostasis, serum lipids, and abdominal adipose tissue distribution in PI-treated and PI-naïve HIV-infected children.
Methods: Study patients were recruited from consenting PI-treated and PI-naïve HIV-infected children 3-18 years of age. Metabolic evaluation included measurement of fasting serum total (T), HDL and LDL cholesterol ©, triglycerides (TG), glucose, insulin, proinsulin, and C-peptide as well as a single slice abdominal CT scan. Insulin resistance (IR) was estimated using the homeostatic model assessment-insulin resistance (HOMA-IR). Insulin sensitivity (IS) was determined using a frequent sampling intravenous glucose tolerance test for a subset of PI-treated children.
Results: 30 PI-treated and 20 PI-naïve subjects were included. The mean age, viral load, and CD4 count were 8.6 years, 14,602 copies/mL and 1004 cells/muL for PI-treated and 9.2 years, 18,274 copies/mL and 723 cells/muL for PI-naïve subjects. PI-treated children had received PIs for a mean duration of 22.6 months (range 8-46). Fasting serum TC, LDLC, and TG but not glucose, insulin, proinsulin or C-peptide levels were significantly higher in PI-treated than PI-naïve children. HDLC was similar in the 2 groups. The mean TC, LDLC, and TG in PI-treated and PI-naïve children were 5.13 mmol/L (range 3.37-10.78), 3.26 mmol/L (range 1.59-8.30), and 1.83 mmol/L (range 0.67-6.84) and 4.02 mmol/L (range 2.81-5.41), 2.48 mmol/L (range 1.38-4.02), and 0.98 mmol/L (range 0.41-2.41), respectively. HOMA-IR and visceral to subcutaneous adipose tissue (V/SC) ratio were similar in the 2 groups. Reduced IS (IS index <0.5x10-4[pmol/L]-1min-1) was demonstrated in 30% (7/23) of PI-treated children (mean 1.08, range 0.04-4.7). IS correlated negatively with age (p = 0.0099) and V/SC ratio (p = 0.0073), but did not correlate with duration of PI therapy, d4T exposure, viral load, or CD4 count.
Conclusions: In HIV-infected children, PI therapy is associated with elevated levels of TC, LDLC, and TG but not with IR or visceral adipose tissue accumulation. In PI-treated children IS is closely associated with age and visceral adiposity but not with duration of PI therapy or d4T exposure.
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