The effect of zidovudine on skeletal muscle mtDNA in HIV-1 infected patients with mild or no muscle dysfunction

J. Casademont, A. Barrientos, J. M. Grau, E. Pedrol, X. Estivill, A. Urbano-Márquez, V. Nunes

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Zidovudine (ZDV), a nucleoside analogue which inhibits viral replication, is currently used in the treatment of type I human immunodeficiency virus (HIV-1) infection. It has been considered to be the cause of an acquired form of myopathy associated with a depletion of mitochondrial DNA (mtDNA) in muscle fibres, although the fact that the patients previously studied were clearly symptomatic, and the theoretical difficulty in differentiating an HIV-related myopathy from the effects of ZDV, led to a controversy on the possible deleterious effect of ZDV on muscle fibres. We studied the muscle biopsy taken from 42 HIV-I infected patients, regardless of their medical complaints, and two series of controls. 12 HIV-negative patients suffering from diverse neuromuscular diseases and 10 normal patients who underwent orthopaedic surgery. Whole DNA was extracted following standard procedures and analysed by means of Southern blotting and polymerase chain reaction (PCR). We found that mtDNA was only depleted in HIV-1 infected patients treated with ZDV, but not in controls or patients untreated with this antiretroviral drug. Moreover, the depletion was more marked in patients who either presented weakness, myalgia, raised serum creatine kinase (CK), or ragged-red fibres. Mitochondrial DNA deletions were found in low proportion in all groups of patients, regardless of their HIV infection or ZDV status, but not in normal controls. We conclude that ZDV treatment in HIV-1 positive patients produces depletion of muscle mtDNA. The depletion can be demonstrated even in asymptotic patients, but is more marked in patients with clinical symptoms or abnormalities in their muscle biopsies. Other mtDNA abnormalities such as deletions seemed to be more related to other circumstances concurring in HIV-1 infected patients than to the effects of ZDV.

Original languageEnglish (US)
Pages (from-to)1357-1364
Number of pages8
JournalBrain
Volume119
Issue number4
DOIs
StatePublished - Aug 1996
Externally publishedYes

Keywords

  • HIV
  • Mitochondrial DNA
  • Skeletal muscle
  • Zidovudine

ASJC Scopus subject areas

  • Neuroscience(all)

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    Casademont, J., Barrientos, A., Grau, J. M., Pedrol, E., Estivill, X., Urbano-Márquez, A., & Nunes, V. (1996). The effect of zidovudine on skeletal muscle mtDNA in HIV-1 infected patients with mild or no muscle dysfunction. Brain, 119(4), 1357-1364. https://doi.org/10.1093/brain/119.4.1357