Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy.
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.
Arnaudo
E
E
Department of Neurology, Columbia University College of Physicians and Surgeons, New York.
Dalakas
M
M
Shanske
S
S
Moraes
C T
CT
DiMauro
S
S
Schon
E A
EA
D001345:Autoradiography; D015342:DNA Probes; D004261:DNA Replication / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004334:Drug Administration Schedule; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D008931:Mitochondria, Muscle / Q000737:chemistry* / Q000187:drug effects; D009220:Myositis / Q000139:chemically induced*; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects*
D015342:DNA Probes; D004272:DNA, Mitochondrial; D015215:Zidovudine