Cytochrome c oxidase reaction improves histopathological assessment of zidovudine myopathy

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Abstract
Zidovudine can induce a mitochondrial myopathy with ragged-red fibers and partial cytochrome c oxidase deficency. In an attempt to improve histological assessment of zidovudine myopathy, we evaluated cytochorme c oxidase histochemical reaction in the muscle of 10 patients with biopsy-proven zidovudine myopathy (Group 1), 10 myopathic immunodeficiency virus (HIV)-infected patients not treated by zidovudine who had an immunohistological profile of HIV-associated myopathy or other neuromuscular disorders (Group 3). Among zidovudine receivers, cytochrome c oxidase deficiency was found in 10 of 10 patients from Group 1 and 7 of 10 from Group 2. No cytochrome c oxidase deficiency was observed in patients not treated by zidovudine. When present, cytochrome c oxidase-negative fibers accounted for 2 to 28% of fibers, and there was no difference for the number of cytchrome c oxidase-negative fibers between Group 1 and Group 2. Most patients with cytochrome c oxidase deficiency that could be evaluated clinically after muscle biopsy improved after withdrawal of zidovudine (5 of 7 in Group 1,5 of 5 in Group 2). Patients who did not improve had an HIV-associated myopathy concurrently with zidovudine myopathy. We conclude that cytochrome c oxidase reaction may be used as a reliable marker of zidovudine mitochondrial toxicity in HIV-infected patients with muscular symptoms.