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Update on mitochondrial toxicity: where are we now?
1Medizinische Universitätsklinik, Department of Rheumatology and Clinical Immunology, Hugstetterstrasse 55, D-79106 Freiburg, Germany.
Journal of HIV Therapy
|July 3, 2003
Summary
Prolonged use of antiretroviral nucleoside analogue reverse transcriptase inhibitors (NRTIs) can cause mitochondrial toxicity, affecting metabolism and organs like the liver and nerves. Stopping the offending NRTI is the most effective treatment for established toxicity.
Area of Science:
- Pharmacology
- Toxicology
- Metabolism
Background:
- Long-term use of antiretroviral nucleoside analogue reverse transcriptase inhibitors (NRTIs) is linked to metabolic alterations.
- NRTIs exhibit varying mechanisms, potencies, and tissue specificities regarding mitochondrial toxicity.
Purpose of the Study:
- To review the mechanisms and clinical manifestations of NRTI-induced mitochondrial toxicity.
- To highlight target organs, potential adverse effects, and management strategies for NRTI-induced mitochondrial dysfunction.
Main Methods:
- Literature review of studies on NRTI mechanisms and mitochondrial toxicity.
- Analysis of clinical observations and case reports related to NRTI adverse effects.
Main Results:
- Certain NRTIs ('d-drugs') inhibit mitochondrial DNA polymerase, leading to mtDNA depletion in organs like the liver and nerves.
- Zidovudine can cause hyperlactataemia and mitochondrial encephalomyopathies, particularly with perinatal exposure.
- Tenofovir accumulation in renal tubules may lead to renal failure and Fanconi syndrome.
- Mitochondrial toxicity monitoring and prediction remain challenging.
Conclusions:
- Cessation of the causative NRTI is the primary intervention for established mitochondrial toxicity.
- Caution is advised when co-administering potentially toxic drugs like valproate.
- Interactions between specific NRTIs (e.g., didanosine) and other medications require careful consideration.