The drugs used to treat HIV infection (antiretrovirals, or ARV's) are known to be toxic to the mitochondria, the "batteries of the cells." So far, research has focused on the negative effects or ARV's on only one aspect of the mitochondria: oxidative phosphorylation (OXPHOS). An expanded view of the mitochondria suggests that dozens of other metabolic pathways are dependant on OXPHOS and may also be perturbed as a result of ARV's. This disruption of metabolic health is likely to be associated with clinical problems, as is seen in chidren with inborn errors of metabolism (congenital, severe defects in metabolic pathways) and may even be amenable to treatment that is available for children with inborn errors of metabolism. A complete understanding of the adverse effects of ARV's is essential as we enter an era of expanded access to HIV treatment worldwide.
We think that children exposed to ARV's will have a higher rate of dysfunction in the metabolism of fats and protein and that there may be a blood or genetic test that can identify the at-risk patients so they can be helped. The first step is to define the extent of the problem. To do so, we are going to use fresh and frozen samples of blood serum and DNA to perform tests that are usually used in the management of inborn errors of metabolism to define the extent of metabolic dysfunction in ARV-exposed children and analyze the results for a pattern which will tell us which children are at risk and how we might be able to treat them. This is urgent in an era when HIV infection can be controlled with medications, but the long-term health effects of those medications are not completely understood.