Urgent need for guidance on management of heart disease risk in HIV-positive children

The majority of HIV-positive children who develop high cholesterol still have elevated cholesterol two years later, US investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

Only a quarter of children with elevated cholesterol changed their HIV therapy and few received statins or other lipid-lowering drugs.

The investigators express concern that “there are no published guidelines about what lipid levels should prompt pharmacologic intervention in HIV-infected children.”

High cholesterol is common in HIV-positive adults and children. It has a number of causes, including the side-effects of some antiretroviral drugs.

HIV-positive children face a lifetime of antiretroviral therapy, and having elevated cholesterol can increase the long-term risk of cardiovascular disease. This is increasingly important cause of serious illness and death in patients with HIV.

Investigators from the US PACTG 219C study therefore wished to establish the prevalence, incidence, clinical course, and management of elevated cholesterol in HIV-positive children.

Recruitment to the study occurred between 2000 and 2006, and final follow-up was in May 2007. The 2,581 children enrolled in the study were monitored at three-monthly intervals.

Children were defined as having prevalent elevated cholesterol if their cholesterol was 220 mg/dl (5.68 mmol/l) or above on recruitment to the study.

Incident elevated cholesterol was diagnosed if cholesterol was normal at baseline but then increased to above 220 mg/dl on two successive occasions.

Reversion of cholesterol to normal levels was defined as a fall to below 200 mg/dl (5.17 mmol/l) on two successive occasions.

A total of 342 children had high cholesterol when they entered the study, and 282 individuals developed cholesterol above 220 mg/dl during follow-up.

Approximately half of each group were boys and of black race.

Few children received therapy with lipid lowering agents. Only 26 individuals were treated with statins and a further nine were treated with fibrates.

“We were unable to determine the effect of statins on cholesterol levels as we did not have enough follow-up cholesterol values after children began statins,” note the authors, “we also did not have enough information to determine how long statins were taken and if the children were adherent.”

During two-years of follow-up, only 27% of children with elevated cholesterol changed their antiretroviral therapy.

Just over a third (34%) of children with incident elevated cholesterol had a sustained fall in the level of their cholesterol to below 220 mg/dl.

“The majority of children with incident hypercholesterolemia failed to demonstrate resolution of elevated cholesterol over two years of follow-up,” comment the investigators.

A similar proportion (31%) of children with elevated cholesterol at baseline experienced a reversion of their cholesterol to normal levels.

Children aged over 13 years were significantly more likely to revert to normal cholesterol levels (adjusted hazard ratio [aHR] = 2.4; 95% CI, 1.3-4.3), as were individuals who changed their antiretroviral therapy (aHR = 2.4; 95% CI, 1.5-3.9).

“Change in ARV [antiretroviral] regimen was associated with a decrease in cholesterol, but it is difficult to attribute the decrease to a specific class or agent in this cohort,” write the authors.

The authors of an accompanying editorial believe the study emphasises “the urgent need to develop guidelines specifically for HIV-infected children, where there is an opportunity to minimize CVD risk early.”

They suggest that a combined approach will probably achieve the best results, and include the use of lipid-friendly anti-HIV drugs, “along with aggressive lifestyle and pharmacologic interventions.”

They conclude, “formal guidelines are the first crucial step in minimizing CVD complications and maximizing quality of life in this vulnerable population.”

Jacobson DL et al. Clinical management and follow-up of hypercholesterolemia among perinatally HIV-infected children enrolled in the PACTG 219C study. J Acquir Immune Defic Syndr, online edition, doi: 10. 1097/QAI.0b013e31822203f5, 2011.

Ross AC et al. Cardiovascular risk in pediatric HIV: the need for population-specific guidelines. J Acquir Immune Defic Syndr, online edition, doi: 10. 1097/QAI.0b013e3182227b016, 2011.