Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction.
Muscle biopsy specimens were obtained from 48 human immunodeficiency virus-infected patients suffering from various neuromuscular symptoms. Microscopic examination by conventional and electron microscopy revealed a characteristic structural myopathy associated with mitochondrial changes in 13 patients, all of whom had received long-term zidovudine therapy. The mean cumulative dose they had received (498 +/- 145 gm) was significantly higher than that of the other 14 zidovudine recipients of the study. They suffered from a progressive, usually painful, proximal myopathy with pronounced wasting, normal-to-moderately elevated creatine kinase levels, and a myopathic electromyographic pattern. The condition usually improved after withdrawal of the drug. Assay of mitochondrial enzymes, including succinate-cytochrome c reductase, cytochrome c oxidase, and citrate synthase, showed a decline in respiratory chain capacity. Southern blot analysis of mitochondrial DNA showed no abnormality. It is likely that mitochondrial dysfunction, probably resulting from drug-induced inhibition of the mitochondrial DNA polymerase, is implicated in the pathogenesis of this complication of zidovudine therapy.
Mhiri
C
C
Département de Pathologie (Unités de Médecine Légale et de Neuropathologie), Hôpital Henri Mondor, Créteil, France.
Baudrimont
M
M
Bonne
G
G
Geny
C
C
Degoul
F
F
Marsac
C
C
Roullet
E
E
Gherardi
R
R
D000328:Adult; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors; D004261:DNA Replication / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000096:biosynthesis; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D009132:Muscles / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology; D010085:Oxidative Phosphorylation; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
D004272:DNA, Mitochondrial; D015215:Zidovudine; D004258:DNA Polymerase III