Metabolic abnormalities in protease inhibitor-treated and protease naïve children

There is currently a paucity of data pertaining to what is broadly termed the lipodystrophy syndrome, in children. A report published in AIDS compares the glucose homeostasis and serum lipid profiles of PI-treated and PI-naïve HIV-positive children and the abdominal adiposal tissue distribution of PI–treated, PI –naïve and HIV-negative children.

This was a cross-sectional study involving HIV-positive children (30 PI-treated, 20 PI-naïve), three–18 years of age, 76% prepubertal, in a paediatric tertiary care centre. PI treated was defined as treatment for a minimum of three months prior to enrolment. The mean duration of PI therapy in the PI group was 22 –/+8.9 months. PI treated was defined as receiving HAART plus at least two non-PI drugs. The children were receiving ritonavir (n=12), nelfinavir (n=13), indinavir (n=2), lopinavir (n=1), ritonavir+nelfinavir (n=1), and nelfinavir+saquinavir (n=1). In the PI-naive group four were antiretroviral naïve, 14 were on two NRTI and two were on two NRTI and an NNRTI. A group of 52 uninfected underwent CT scan as an additional comparison with respect to abdominal tissue distribution.

Total, HDL and LDL-cholesterol, triglycerides, glucose, insulin, proinsulin and C-peptide were determined in the fasting state. Insulin resistance was assessed using the homeostatic model assessment–insulin resistance (HOMA–IR). Abdominal adipose tissue distribution was determined by single-slice computed tomography at the umbilical level.

The investigators found that PI-treated children had significantly higher total cholesterol (p= 0.0021), LDL-cholesterol (p= 0.019) and triglycerides (p= 0.0018). Serum glucose, insulin, proinsulin and C-peptide, the insulin: glucose ratio, insulin resistance, estimated by the homeostatic model assessment-insulin resistance (HOMA–IR) and abdominal adipose tissue distribution were similar in both groups.

They reported that viral load, CD4 cell count and stavudine therapy were not significantly associated with serum lipids, insulin resistance or abdominal adipose tissue distribution. The strongest predictor associated with fasting serum insulin and HOMA–IR was the Tanner stage, which is the most widely used clinical scale for assessing pubertal development. Age was the most significant predictive variable of the visceral: subcutaneous adipose tissue ratio.

The investigators concluded that in this cohort of predominantly prepubertal HIV-positive children “PI therapy was associated with an atherogenic dyslipidemia but not with insulin resistance or abnormal abdominal adipose tissue distribution.” and that “the results suggest that children, particularly prepubertal children, are less susceptible than adults to PI-induced changes in glucose homeostasis and abdominal adipose tissue distribution.” They also write “…routine monitoring of serum lipids in all HIV-infected children, particularly those receiving PI therapy, is warranted.”

Bitnuna A, Sochettb E, Babync P et al. Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor-treated and naive HIV-infected children. AIDS 2003, 17:1319–1327

Comment

This is a useful study that may add to the arguments in favour of PI-sparing regimens for children. However, we do not yet know the long-term implications of the raised lipids for children.

Non-invasive methods of monitoring such as flow-mediated dilation in coronary and brachial arteries which correlates with endothelial dysfunction may be useful.

[Takase B, Uehata A, Akima T, et al. Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Card. 1998; 82: 1535-9]