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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. |
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