Partial cytochrome c oxidase deficiency and cytoplasmic bodies in patients with zidovudine myopathy.

A histochemical study of cytochrome c oxidase (CCO) was performed in the muscles from eight patients with full-blown zidovudine myopathy. All patients had ragged-red fibres (total cumulative count: 160) and myofilamentous changes, that predominated in type 1 fibres and included diffuse or punch-out myofibrillar loss (75 affected fibres) and constant cytoplasmic body formation (106 affected fibres). Inflammatory infiltrates were present in four out of eight patients. A partial CCO deficiency (22-47% of fibres; both types 1 and 2 affected) was detected in all cases, and contrasted with the normal or increased succinate dehydrogenase activity observed in most fibres. Among CCO-deficient fibres, 71% were normal on trichrome, but all ragged-red fibres were CCO-negative. Myofilamentous changes were restricted to CCO-deficient fibres. The present study strongly supports the idea that mitochondrial toxicity is the specific mechanism of zidovudine myopathy.