Lipid monitoring and cholesterol management also essential for children with HIV, US study suggests

Michael Carter
Published: 18 March 2005

A total of 13% of HIV-positive children and adolescents have elevated cholesterol, according to a US study published in the April 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators found that treatment with a protease inhibitor, perfect adherence, and a viral load below 400 copies/ml were strongly associated with elevated cholesterol, and believe that their findings support the ongoing monitoring of lipids in children taking protease inhibitors as well as have implications for the choice of antiretroviral treatment regimens.

It is well established that protease inhibitors disturb the lipid metabolism in adults, leading to elevated levels of cholesterol and triglycerides. Several cross sectional studies have produced similar findings in protease inhibitor-treated HIV-positive treatment. However, these studies have been limited by sample size and methodological problems.

Investigators from the US Pediatric AIDS Clinical Trials Group 219C study sought to determine the prevalence of elevated cholesterol amongst HIV-positive and HIV-negative children exposed to HIV at birth and to describe the association between elevated cholesterol and a number of factors, including the use of antiretroviral therapy.

The investigators hypothesised that elevated cholesterol would be more common among older children with longer duration of exposure to protease inhibitors, and with excellent adherence to therapy. They also theorised that it would be associated with high blood pressure and obesity.

A total of 1999 children and adolescents aged four to 19 years, recruited from 75 sites in the US and Puerto Rico, were included in the investigators’ analysis. In total, 1812 were HIV-positive, 56% were black, 60% were aged between six and twelve, 25% had an AIDS diagnosis, 67% had a CD4 cell percentage of 25% or more, 77% had a viral load below 400 copies/ml and, in general, were underweight.

Of the HIV-positive children, 13% had elevated cholesterol compared to 5% of the HIV-negative children.

In multivariate analysis, current use of a protease inhibitor (OR = 6.2, p = 0.001), a viral load below 400 copies/ml (OR = 3.09, p < 0.001), perfect self-reported adherence in the previous three days (OR = 2.4, p = 0.001), age under twelve years (p = 0.001), white or Hispanic ethnicity (p = 0.001), and current use of an NNRTI (OR = 1.6, p = 0.002) were all significantly and independently associated with elevated cholesterol. Although elevated systolic blood pressure was associated with increased cholesterol in univariate analysis, this ceased to be significant when confounding variables were controlled for in multivariate analysis. In neither univariate nor multivariate analysis was an association found between body mass index and elevated cholesterol.

The investigators comment that they found “a robust association between hypercholesterolemia and current use protease inhibitor use”. They add that it is “sobering that those children who have achieved the virologic goal of therapy have the highest hypercholesterolemia prevalence…this association with adherence has previously been reported in an adult study and suggests that this group of patients should be targeted for careful lipid monitoring.

Limitations with the study are, however, acknowledged by the investigators, in particular their reliance on elevated total cholesterol as the sole measure of lipid disturbance. Further, blood samples to measure total cholesterol were not obtained after an over-night fast.

“We found that the prevalence of hypercholesterolemia among perinatally HIV-infected children in out study was 13%. Hypercholesterolemia was most strongly associated with the use of protease inhibitors but was also significantly associated with HIV viral load below 400 copies/ml, younger age, self-report…of perfect adherence, white or Hispanic ethnicity, and current NNRTI use”, conclude the investigators. They recommend that children receiving protease inhibitors should have their lipids carefully monitored and that the risk of increased cholesterol should be remembered when making treatment choices.

Reference

Farley J et al. Prevalence of elevated cholesterol and associated risk factors among perinatally HIV-infected children (4 – 19 years old) in Pediatric AIDS Clinical Trials Group 219 C. J Acquir Immune Defic Syndr 38: 480 – 487, 2005.

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