Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy

E. Arnaudo, S. Shanske, S. DiMauro, E. A. Schon, C. T. Moraes, E. A. Schon, M. Dalakas

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Abstract

Long-term zidovudine therapy in patients with human immunodeficiency virus (HIV) infection can cause a destructive mitochondrial myopathy with histological features of ragged-red fibres (RRF) and proliferation of abnormal mitochondria. In 9 zidovudine-treated patients with this myopathy we found severely reduced amounts (up to 78% reduction vs normal adult controls) of mitochondrial DNA (mtDNA) in muscle biopsy specimens by means of Southern blotting. In 2 HIV-positive patients who had not received zidovudine, muscle mtDNA content did not differ from that in the 4 controls. Depletion of mtD NA seems to be reversible, since 1 patient showed a substantial reduction in RRF and a concomitant pronounced increase in muscle mtDNA content after zidovudine therapy was discontinued. Depletion of muscle mtDNA is probably due to zidovudine-induced inhibition of mtDNA replication by DNA polymerase gamma and is not a secondary effect of HIV infection.

Original languageEnglish (US)
Pages (from-to)508-510
Number of pages3
JournalThe Lancet
Volume337
Issue number8740
DOIs
StatePublished - Mar 2 1991
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Arnaudo, E., Shanske, S., DiMauro, S., Schon, E. A., Moraes, C. T., Schon, E. A., & Dalakas, M. (1991). Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. The Lancet, 337(8740), 508-510. https://doi.org/10.1016/0140-6736(91)91294-5