Sixth International Congress Drug Therapy in HIV Infection 17-21 November, 2002 Glasgow, UK

Purpose of the study: Tolerance of perinatal antiretroviral prophylaxis remains to be assessed on a large scale and in the long term. The possibility of mitochondrial toxicity remains contested.

Methods: Exhaustive study in a large prospective cohort, and using a predetermined algorithm, of the unexplained symptoms compatible with mitochondrial dysfunction among HIV-uninfected children. 2644/4392 were perinatally exposed to antiretroviral drugs. Complementary radiological, enzymological and pathological analyses on a case-by-case. Classification according to a diagnostic probability scale for mitochondrial dysfunction, based on experience with constitutional mitochondrial diseases. Spontaneous notification register for children born to HIV seropositive mother not included in the cohort with similar symptoms.

Results: Twelve children were classified as having ”established” unambiguous mitochondrial dysfunction. Seven of these children were from the prospective cohort, the remaining five were children not included in the cohort. All presented neurological symptoms, in many cases associated with abnormal cerebral MRI findings (10/12) and/or a significant episode of hyperlactatemia (7/12). All had either a profound deficit in one of the respiratory chain complexes (11/12) and/or a histological pattern typical of mitochondrial dysfunction (2/12). All were perinatally exposed to antiretroviral drugs. Fourteen other children in the cohort, all of whom were exposed to antiretrovirals, had unexplained symptoms, mostly neurological, for which one of the possible differential diagnoses was mitochondrial dysfunction. Close similarities in clinical, neuroradiological and histological findings strongly suggest a common pathological process in all these 26 children. In addition to histological findings consistent with mitochondrial dysfunction observed in 17/19 muscular biopsies, enlarged endothelial cells with abnormal mitochondria were identified on 9/18 electron microscopy studies.

Conclusions: Conclusion Children exposed to nucleoside analogues during the perinatal period are at risk of a neurological/biochemical syndrome associated with persistent mitochondrial dysfunction.

Presenting author: Stéphane Blanche

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1 On behalf of the French Prospective Cohort, Paris, France.

2002-11-17
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