11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11:abstract no. 48

Stéphane Blanche
Hosp Necker, Paris, France

BACKGROUND: Mitochondrial toxicity of some nucleoside analogues, when used alone or in association, is now well established. These molecules can cross the placenta, such that the foetus is often exposed for several months. There is no reason to believe that the fetus or the infant is not subject to this phenomenon. Ultrastructural and enzymatic mitochondrial anomalies have been observed in several organs including the brain in a monkey model of in utero exposure, but the clinical significance of these findings for humans is still unknown. In several cohorts, about 30% of exposed children present hyperlactatemia during the treatment period. This sometimes regresses slowly after treatment withdrawal. Two studies have demonstrated a reduction in the amount of mitochondrial DNA in the peripheral blood leukocytes of exposed children. Recently, ultrastructural examination also revealed mitochondrial anomalies in umbilical cord endothelial cells. It is not yet known whether this toxicity is fully reversible. Cases in the French cohort of persistent mitochondrial dysfunction with neurological symptoms have been described in detail. Such cases are rare (0.3% of exposed children), but 50 to 100 times more frequent than similar mitochondrial conditions in the general population. To date the only risk factor for such toxicity is perinatal exposure to zidovudine, but other risk factors-genetic, pharmacologic, etc.-remain to be identified.

CONCLUSIONS: It is now important to compare the mitochondrial effects of different molecules and associations in infants to maximize tolerance to this very beneficial prophylactic treatment.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.