Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy

Area of Science:

• Neurology
• Pathology
• Virology

Background:

• Zidovudine (ZDV) is a nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus (HIV) infection.
• A potential side effect of ZDV is mitochondrial myopathy, but its distinction from HIV-associated myopathy is debated.
• Mitochondrial abnormalities have been observed in HIV patients, regardless of ZDV treatment.

Purpose of the Study:

• To investigate whether zidovudine (ZDV) induces a mitochondrial myopathy distinguishable from human immunodeficiency virus (HIV)-associated myopathy in ZDV-naive patients.
• To evaluate the correlation between mitochondrial abnormalities, ZDV exposure, and clinical myopathy severity in HIV-infected individuals.

Main Methods:

• Skeletal muscle biopsies were obtained from 18 HIV-positive, ZDV-exposed patients and 9 HIV-positive, ZDV-naive patients, all with clinical myopathy.
• Muscle samples were analyzed using light and electron microscopy by blinded evaluators.
• Neuromuscular evaluations, including ZDV timing and dosage, were recorded for all participants.

Main Results:

• Mitochondrial abnormalities were present in both ZDV-treated and ZDV-naive patient groups.
• The observed mitochondrial abnormalities did not correlate with ZDV exposure or cumulative dosage.
• Mitochondrial abnormalities showed a significant correlation with the presence and severity of myofiber degeneration, irrespective of ZDV status.

Conclusions:

• Mitochondrial abnormalities in HIV-infected patients appear to reflect myofiber degeneration rather than primary mitochondrial dysfunction caused by ZDV.
• The findings suggest that mitochondrial abnormalities are not a reliable indicator of ZDV-induced mitochondrial myopathy in this population.
• The underlying cause of myofiber degeneration in HIV infection, whether ZDV-exposed or not, remains undetermined.