Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues

Background Zidovudine is commonly administered during pregnancy to prevent mother-to-child HIV-transmission. We investigated mitochondrial toxic effec ts in children exposed to zidovudine in utero and after birth. Methods We analysed observations of a trial of tolerance of combined zidovu dine and lamivudine and preliminary results of a continuing retrospective a nalysis of clinical and biological symptoms of mitochondrial dysfunction in children born to HIV-1-infected women in France. Mitochondrial dysfunction was studied by spectrophotometry and polarography of respiratory-chain com plexes in various tissues. Findings Fight children had mitochondrial dysfunction. Five, of whom two di ed, presented with delayed neurological symptoms and three were symptom-fre e but had severe biological or neurological abnormalities. Four of these ch ildren had been exposed to combined zidovudine and lamivudine, and four to zidovudine alone. No child was infected with HIV-1. All children had abnorm ally low absolute or relative activities of respiratory-chain complexes I, IV, or both months or years after the end of antiretroviral treatment. No m utation currently associated with constitutional disease was detected in an y patient. Interpretation Our findings support the hypothesis of a link between mitoch ondrial dysfunction and the perinatal administration of prophylactic nucleo side analogues. Current recommendations for zidovudine monotherapy should h owever be maintained. Further assessment of the toxic effects of these drug s is required.