Depletion of Muscle Mitochondrial DNA in AIDS Patients With Zidovudine-Induced Myopathy

Lancet. 1991 Mar 2;337(8740):508-10. doi: 10.1016/0140-6736(91)91294-5.

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 mtDNA 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoradiography
  • DNA Probes
  • DNA Replication / drug effects
  • DNA, Mitochondrial / drug effects*
  • Drug Administration Schedule
  • HIV Seropositivity / drug therapy*
  • Humans
  • Mitochondria, Muscle / chemistry*
  • Mitochondria, Muscle / drug effects
  • Myositis / chemically induced*
  • Zidovudine / administration & dosage
  • Zidovudine / adverse effects*

Substances

  • DNA Probes
  • DNA, Mitochondrial
  • Zidovudine