Zidovudine administration during pregnancy and mitochondrial disease in the offspring

Pier Angelo Tovo, Nadia Chiapello, Clara Gabiano, Massimo Zeviani, Marco Spada

Research output: Contribution to journalArticle

Abstract

Prophylactic administration of zidovudine (ZDV) to mother-child pairs reduces HIV transmission. ZDV can impair mitochondrial (mt) DNA polymerase γ, leading to mtDNA depletion. Signs of mitochondrial dysfunction have been observed in a few children with prenatal exposure to nucleoside analogues, although no mtDNA depletion was demonstrated. Other studies failed to confirm mitochondrial disorders in children who were exposed to antiretroviral agents in utero. A child, whose HIV-infected mother received ZDV from the fourth month of pregnancy, developed neonatal encephalomyopathy, anaemia and hyperlactataemia. At 2 weeks of age, a muscle biopsy exhibited red-ragged-like fibres, proliferation of abnormal mitochondria and a 90% depletion of mtDNA without qualitative abnormalities. At 6 months, the depletion was less profound (about 50% of normal values). Severe psychomotor delay and visual disturbances persisted at 30 months, but they were greatly reduced at 5-year follow-up. These laboratory and clinical findings clearly demonstrated that mtDNA alteration was acquired and not consequent to an inherited disorder. Fetal exposure to ZDV may have caused the mtDNA depletion, which, although temporary, led to irreversible but not progressive brain damage.

Original languageEnglish
Pages (from-to)697-699
Number of pages3
JournalAntiviral Therapy
Volume10
Issue number6
Publication statusPublished - 2005

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Mitochondrial Diseases
Zidovudine
Mitochondrial DNA
Pregnancy
Neonatal Anemia
Mothers
HIV
Anti-Retroviral Agents
DNA-Directed DNA Polymerase
Nucleosides
Mitochondria
Reference Values
Biopsy
Muscles
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tovo, P. A., Chiapello, N., Gabiano, C., Zeviani, M., & Spada, M. (2005). Zidovudine administration during pregnancy and mitochondrial disease in the offspring. Antiviral Therapy, 10(6), 697-699.

Zidovudine administration during pregnancy and mitochondrial disease in the offspring. / Tovo, Pier Angelo; Chiapello, Nadia; Gabiano, Clara; Zeviani, Massimo; Spada, Marco.

In: Antiviral Therapy, Vol. 10, No. 6, 2005, p. 697-699.

Research output: Contribution to journalArticle

Tovo, PA, Chiapello, N, Gabiano, C, Zeviani, M & Spada, M 2005, 'Zidovudine administration during pregnancy and mitochondrial disease in the offspring', Antiviral Therapy, vol. 10, no. 6, pp. 697-699.
Tovo, Pier Angelo ; Chiapello, Nadia ; Gabiano, Clara ; Zeviani, Massimo ; Spada, Marco. / Zidovudine administration during pregnancy and mitochondrial disease in the offspring. In: Antiviral Therapy. 2005 ; Vol. 10, No. 6. pp. 697-699.
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