Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy.
There is controversy as to whether zidovudine (ZDV) induces a mitochondrial myopathy that is distinguishable from human immunodeficiency virus (HIV)-associated myopathy in ZDV-naive patients. Mitochondrial abnormalities were evaluated in skeletal muscle obtained from 18 HIV-positive, ZDV-exposed patients, and 9 who were drug naive. All patients had clinical myopathy, and underwent neuromuscular evaluation with information recorded on timing and dosage of ZDV. All underwent muscle biopsies and samples were examined without knowledge of clinical history or ZDV status. Biopsy samples were evaluated by light and electron microscopy. Mitochondrial abnormalities were seen in ZDV-treated and -naive groups, and did not correlate with ZDV exposure or cumulative ZDV dosage. Mitochondrial abnormalities displayed significant correlation with the presence and severity of myofiber degeneration on biopsy, regardless of ZDV status. As mitochondrial abnormalities reflect myofiber degeneration, present in both patient groups, they may not be used as evidence of primary mitochondrial dysfunction. The etiology of myofiber degeneration in patients with HIV infection, whether ZDV-exposed or -naive, remains unclear.
Morgello
S
S
Department of Pathology (Division of Neuropathology, Mount Sinai Medical Center, New York City, NY 10029, USA.
Wolfe
D
D
Godfrey
E
E
Feinstein
R
R
Tagliati
M
M
Simpson
D M
DM
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000648:ultrastructure*; D018485:Muscle Fibers, Skeletal / Q000648:ultrastructure; D018908:Muscle Weakness / Q000473:pathology; D009132:Muscles / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000209:etiology / Q000473:pathology*; D010146:Pain / Q000209:etiology / Q000473:pathology; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D000998:Antiviral Agents; D015215:Zidovudine; D003402:Creatine Kinase