ZIDOVUDINE-INDUCED MITOCHONDRIAL MYOPATHY IS ASSOCIATED WITH MUSCLE CARNITINE DEFICIENCY AND LIPID STORAGE

The use of zidovudine (AZT) for the treatment of acquired immunodefici ency syndrome (AIDS) induces a DNA-depleting mitochondrial myopathy, w hich is histologically characterized by the presence of muscle fibers with ''ragged-red''-like features, red-rimmed or empty cracks, granula r degeneration, and rods (AZT fibers). Because dysfunctioning muscle m itochondria may lead to defects of beta-oxidation of fatty acids, we e xamined the degree of neutral fat accumulation and muscle carnitine le vels in the muscle biopsy specimens from 21 patients with AZT-induced myopathic symptoms of varying severity. Six patients with no AZT fiber s had normal endomyofibrillar lipid deposits and muscle carnitine leve ls; 7 patients with fewer than 5 AZT fibers per field had a mild (+) t o moderate (++) increase in lipid droplets, and reduced muscle carniti ne levels (3 patients); and 8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked (+++) increase in lipid droplet s, and reduced muscle carnitine levels (6 patients). Serial sections s howed lipid globules often within ''cracks'' or vacuoles of the abnorm al muscle fibers. We conclude that the muscle mitochondrial impairment caused by AZT results in (1) accumulation of lipid within the muscle fibers owing to poor utilization of long-chain fatty acids, (2) reduct ion of muscle carnitine levels probably due to decreased carnitine upt ake by the muscle, and (3) depletion of energy scores within the muscl e fibers. The findings may have potential therapeutic implications in the treatment of AZT-induced myopathic symptoms using oral carnitine s upplementation.