Tubular aggregates and partial cytochrome c oxidase deficiency in skeletal muscle of patients with AIDS treated with zidovudine.
We report on two patients, who had myalgias while receiving long-term zidovudine treatment for an HIV infection, in whom muscle biopsy findings included a partial cytochrome c oxidase (CCO) deficiency, a feature of zidovudine myopathy, and tubular aggregates, a finding hitherto unreported in HIV-infected patients. The CCO deficit was observed in 28% and 24% of muscle fibers, respectively. Tubular aggregates were the prominent histopathological feature in patient 1, and were detected by systematic electron microscopy in patient 2. Inflammation and myonecrosis were not detected. In patient 1, the typical mitochondrial and myofibrillar changes of zidovudine myopathy were present and 12% of fibers showed tubular aggregates. The aggregates were not stained at CCO reaction, and 96% of myofibers enclosing tubular aggregates showed a decreased CCO activity. This suggested more than a chance association between mitochondrial dysfunction and the formation of tubular aggregates. We conclude that tubular aggregates are detected in some patients treated by zidovudine, and that the finding could be related to the long-term administration of the drug.
Service de Toxicologie, Hôpital Henri Mondor, Créteil, France.
P
P
Chariot
E
E
Benbrik
A
A
Schaeffer
R
R
Gherardi
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D030401:Cytochrome-c Oxidase Deficiency; D015497:HIV-1; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D009132:Muscles / Q000201:enzymology* / Q000473:pathology; D012508:Sarcolemma / Q000648:ultrastructure; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
D015215:Zidovudine