Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues.

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Title: Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues.
Authors: Blanche, Stephane, Tardieu, Marc, Rustin, Pierre, Slama, Abdelhamid, Barret, Beatrice, Firtion, Ghislaine, Ciraru-Vigneron, Nicole, Lacroix, Catherine, Rouzioux, Christine, Mandelbrot, Laurent, Desguerre, Isabelle, Rotig, Agnes, Mayaux, Marie-Jeanne, Delfraissy, Jean-Francois
Source: Lancet. 9/25/1999, Vol. 354 Issue 9184, p1084-1089. 6p. 1 Black and White Photograph, 3 Charts.
Subjects: Maternal-fetal exchange, Pediatric pharmacology, HIV infection transmission, Drug toxicity, Azidothymidine
Abstract: BackgroundZidovudine is commonly administered during pregnancy to prevent mother-to-child HIV-1 transmission. We investigated mitochondrial toxic effects in children exposed to zidovudine in utero and after birth.MethodsWe analysed observations of a trial of tolerance of combined zidovudine and lamivudine and preliminary results of a continuing retrospective analysis 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 complexes in various tissues.FindingsEight children had mitochondrial dysfunction. Five, of whom two died, presented with delayed neurological symptoms and three were symptom-free but had severe biological or neurological abnormalities. Four of these children had been exposed to combined zidovudine and lamivudine, and four to zidovudine alone. No child was infected with HIV-1. All children had abnormally low absolute or relative activities of respiratory-chain complexes I, IV, or both months or years after the end of antiretroviral treatment. No mutation currently associated with constitutional disease was detected in any patient.InterpretationOur findings support the hypothesis of a link between mitochondrial dysfunction and the perinatal administration of prophylactic nucleoside analogues. Current recommendations for zidovudine monotherapy should however be maintained. Further assessment of the toxic effects of these drugs is required. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues.
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  Data: <searchLink fieldCode="AR" term="%22Blanche%2C+Stephane%22">Blanche, Stephane</searchLink><br /><searchLink fieldCode="AR" term="%22Tardieu%2C+Marc%22">Tardieu, Marc</searchLink><br /><searchLink fieldCode="AR" term="%22Rustin%2C+Pierre%22">Rustin, Pierre</searchLink><br /><searchLink fieldCode="AR" term="%22Slama%2C+Abdelhamid%22">Slama, Abdelhamid</searchLink><br /><searchLink fieldCode="AR" term="%22Barret%2C+Beatrice%22">Barret, Beatrice</searchLink><br /><searchLink fieldCode="AR" term="%22Firtion%2C+Ghislaine%22">Firtion, Ghislaine</searchLink><br /><searchLink fieldCode="AR" term="%22Ciraru-Vigneron%2C+Nicole%22">Ciraru-Vigneron, Nicole</searchLink><br /><searchLink fieldCode="AR" term="%22Lacroix%2C+Catherine%22">Lacroix, Catherine</searchLink><br /><searchLink fieldCode="AR" term="%22Rouzioux%2C+Christine%22">Rouzioux, Christine</searchLink><br /><searchLink fieldCode="AR" term="%22Mandelbrot%2C+Laurent%22">Mandelbrot, Laurent</searchLink><br /><searchLink fieldCode="AR" term="%22Desguerre%2C+Isabelle%22">Desguerre, Isabelle</searchLink><br /><searchLink fieldCode="AR" term="%22Rotig%2C+Agnes%22">Rotig, Agnes</searchLink><br /><searchLink fieldCode="AR" term="%22Mayaux%2C+Marie-Jeanne%22">Mayaux, Marie-Jeanne</searchLink><br /><searchLink fieldCode="AR" term="%22Delfraissy%2C+Jean-Francois%22">Delfraissy, Jean-Francois</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 9/25/1999, Vol. 354 Issue 9184, p1084-1089. 6p. 1 Black and White Photograph, 3 Charts.
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  Data: <searchLink fieldCode="DE" term="%22Maternal-fetal+exchange%22">Maternal-fetal exchange</searchLink><br /><searchLink fieldCode="DE" term="%22Pediatric+pharmacology%22">Pediatric pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22HIV+infection+transmission%22">HIV infection transmission</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+toxicity%22">Drug toxicity</searchLink><br /><searchLink fieldCode="DE" term="%22Azidothymidine%22">Azidothymidine</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: BackgroundZidovudine is commonly administered during pregnancy to prevent mother-to-child HIV-1 transmission. We investigated mitochondrial toxic effects in children exposed to zidovudine in utero and after birth.MethodsWe analysed observations of a trial of tolerance of combined zidovudine and lamivudine and preliminary results of a continuing retrospective analysis 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 complexes in various tissues.FindingsEight children had mitochondrial dysfunction. Five, of whom two died, presented with delayed neurological symptoms and three were symptom-free but had severe biological or neurological abnormalities. Four of these children had been exposed to combined zidovudine and lamivudine, and four to zidovudine alone. No child was infected with HIV-1. All children had abnormally low absolute or relative activities of respiratory-chain complexes I, IV, or both months or years after the end of antiretroviral treatment. No mutation currently associated with constitutional disease was detected in any patient.InterpretationOur findings support the hypothesis of a link between mitochondrial dysfunction and the perinatal administration of prophylactic nucleoside analogues. Current recommendations for zidovudine monotherapy should however be maintained. Further assessment of the toxic effects of these drugs is required. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Text: English
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      – SubjectFull: Pediatric pharmacology
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              Text: 9/25/1999
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