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Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction
C Mhiri1, M Baudrimont, G Bonne
1Département de Pathologie (Unités de Médecine Légale et de Neuropathologie), Hôpital Henri Mondor, Créteil, France.
Annals of Neurology
|June 1, 1991
Summary
Long-term zidovudine therapy in HIV patients can cause painful myopathy with mitochondrial damage. Symptoms often improve after discontinuing zidovudine, suggesting a drug-induced effect.
Area of Science:
- Neurology
- Virology
- Mitochondrial Biology
Background:
- Human immunodeficiency virus (HIV) infection can cause neuromuscular complications.
- Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor used to treat HIV.
- Neuromuscular symptoms are reported in some patients receiving antiretroviral therapy.
Purpose of the Study:
- To investigate the cause of neuromuscular symptoms in HIV-infected patients on zidovudine therapy.
- To characterize the pathological changes in muscle biopsies from these patients.
- To explore the role of mitochondrial dysfunction in zidovudine-induced myopathy.
Main Methods:
- Muscle biopsy analysis using conventional and electron microscopy.
- Biochemical assays of mitochondrial enzyme activity.
- Southern blot analysis of mitochondrial DNA.
- Clinical and electromyographic assessment of patients.
Main Results:
- A characteristic myopathy with mitochondrial changes was observed in 13/48 HIV patients on long-term zidovudine.
- These patients had received higher cumulative doses of zidovudine compared to others.
- Muscle biopsies showed reduced mitochondrial respiratory chain capacity, but no mitochondrial DNA abnormalities.
- Symptoms improved upon drug withdrawal.
Conclusions:
- Zidovudine therapy is associated with a progressive myopathy in some HIV patients.
- Mitochondrial dysfunction, likely due to inhibition of mitochondrial DNA polymerase by zidovudine, is implicated in its pathogenesis.
- This drug-induced myopathy can be reversed by discontinuing zidovudine treatment.