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Polyphenotypic expression of mitochondrial toxicity caused by nucleoside reverse transcriptase inhibitors
Robert F Miller1, Maryam Shahmonesh, Michael G Hanna
1Department of Sexually Transmitted Diseases, Royal Free and University College Medical School, University College London and Camden Primary Care Trust, London, UK. rmiller@gum.ucl.ac.uk
Antiviral Therapy
|August 20, 2003
Summary
Long-term use of nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial toxicity in HIV patients. Stopping NRTIs led to significant clinical and biochemical improvements, demonstrating reversibility.
Area of Science:
- Mitochondrial Medicine
- Virology
- Toxicology
Background:
- Nucleoside reverse transcriptase inhibitors (NRTIs) are crucial for managing HIV infection.
- Long-term NRTI therapy can lead to mitochondrial dysfunction, a known side effect.
- This case highlights a severe, multi-systemic manifestation of NRTI-induced mitochondrial toxicity.
Observation:
- A patient on long-term zidovudine and didanosine presented with lactic acidosis, myopathy, Fanconi-type tubulopathy, pancreatic dysfunction, and neuropathy.
- Muscle biopsy revealed abnormal mitochondria and reduced activity of mitochondrial DNA-encoded respiratory chain enzymes.
- Mitochondrial DNA levels were not significantly depleted, and deletions were minor.
Findings:
- Withdrawal of NRTI therapy resulted in rapid improvement of lactic acidosis, pancreatic dysfunction, and tubulopathy.
- Significant recovery in osteoporosis, myopathy, and neuropathy was observed over six months.
- Histological and biochemical normalization of muscle mitochondria occurred after 14 months.
Implications:
- NRTI-induced mitochondrial toxicity is potentially reversible with early diagnosis and drug cessation.
- This case underscores the importance of monitoring for mitochondrial dysfunction in patients on long-term NRTI therapy.
- Understanding NRTI-related mitochondrial effects can guide safer antiretroviral treatment strategies.