Metabolic problems in children on ARTs found

Solution is finding balance in treatment

Conducting clinical trials involving HIV-infected children is very challenging, so the evidence has slowly trickled in, but researchers now believe HIV infection among children can lead to similar metabolic and other problems long noted in adults with the disease.

Many of the complications recognized as a result of HIV disease and/or treatment, including insulin resistance, lipodystrophy, mitochondrial toxicity, and others, may also appear in HIV-infected children, says Grace McComsey, MD, division chief of the pediatric infectious diseases and rheumatology, and an associate professor of pediatrics and medicine at the Case Western Reserve University in Cleveland, OH.

"Another complication is bone abnormalities, which is especially important in children," McComsey says.

"Adults with HIV seem to be prone to have a loss of bone density or bone mass, and we have done studies in children with HIV where they have had a very high rate of osteopenia and osteoporosis."

The children’s bones were very thin for what is expected at their age, and the investigations could not answer definitively the question of whether the problem was the HIV disease, medication, or both, McComsey says.

"It’s very much a concern, because if you have a teenager with low bone mass, then they won’t reach peak bone mass which is reached at age 30," McComsey says.

"I deal with that problem in the clinic every day; if children have very thin bones they’ll be at risk for fracture, and you can’t restrict their activities very much."

The most rapid bone growth occurs between ages eight and 15, but in HIV-positive children, a recent study showed that 43% to 74% had osteo- penia and 23% to 48% had osteoporosis, he says.

Another recent study has shown that tenofovir disoproxil fumarate (TDF) is associated with decreases in bone mineral density among children infected with HIV and on TDF treatment.1

McComsey also has seen evidence of lipodystrophy and lipatrophy among children in her clinic, and these metabolic problems are particularly difficult for teenagers, she says.

"I know by experience that several of my teenagers, as soon as they start to notice body fat changes and they know it has something to do with HIV drugs, we have a significant difficulty keeping them on the drugs," McComsey says. "Two teenage girls stopped taking the drugs without telling us, and they admitted they were throwing out the pills and telling their parents they were taking them."

On a positive note, the newer antiretrovirals appear to result in less lipodystrophy, McComsey says. "So we’re hoping we won’t see a lot of new cases as we see newer and newer drugs."

HIV-infected children on antiretroviral drugs also appear to be at a higher risk for increased lipid levels and atherosclerosis, McComsey says.

Hyperlipidemia is a problem even in children under age 10, and this is a difficult group to treat because statin drugs have not been approved by the Food and Drug Administration (FDA) for prescriptions to young children, McComsey says.

So pediatricians with HIV patients are put in the dilemma of deciding whether it’s more harmful to give statin drugs to young children with HIV infection or whether it’s more dangerous to leave their lipid levels high, McComsey says.

One study found that there were higher cardiovascular markers in ART-treated HIV-positive children when compared with healthy children.2

The study suggests that children with HIV disease may be at significant risk for atherosclerosis while they are young.2

"We found that HIV-infected children without any other risk factor other than being HIV positive and being on antiretrovirals, had arteries with underlying atherosclerosis," McComsey says. "That’s why my study and other such studies in kids are so important," she adds. "This tells us we shouldn’t stay comfortable with saying the children have high lipids, but don’t worry about them."

McComsey’s study, which measured carotid intima-media thickness, produced evidence that the high lipid levels have a significant effect on the children’s hearts.

In treating HIV infected children, a physician’s challenge is to balance the pros and cons of every treatment, including ARTs, McComsey says.

"If someone has very high lipid levels that I can’t control with diet, then first I try to switch their HIV medications to those less likely to cause this lipemia," McComsey says.

"I’ve been successful in this approach except in one child who I had to start on statins at age nine," McComsey says. "I tried to do strict diet control, which you can imagine in children is a nightmare."

References:

  1. Gafni R, et al. Effect of tenofovir disoproxil fumarate-containing HAART on bone mineral density in HIV-infected children. Presented at the 13th Conference on Retroviruses and Opportunistic Infections, held Feb. 5-8, 2006, in Denver, CO. Abstract: 694.
  2. McComsey G, O’Riordan M, Hazen S, et al. Carotid intima media thickness and cardiovascular markers in HIV-infected children. Presented at the 13th Conference on Retroviruses and Opportunistic Infections, held Feb. 5-8, 2006, in Denver, CO. Abstract: 691.