Iatrogenic mitochondriopathies: a recent lesson from nucleoside/nucleotide reverse transcriptase inhibitors

Area of Science:

• Biochemistry
• Virology
• Toxicology

Background:

• Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are vital for treating HIV and HBV infections.
• NRTIs suppress viral replication but exhibit significant toxicity, primarily mitochondrial damage.
• Mitochondrial toxicity manifests as myopathy, neuropathy, and lactic acidosis, impacting treatment efficacy.

Purpose of the Study:

• To explore the complex mechanisms underlying NRTI-induced mitochondrial toxicity.
• To identify host factors contributing to NRTI mitochondrial toxicity.
• To review current and potential management strategies for NRTI mitochondrial toxicity.

Main Methods:

• Review of existing literature on NRTI mechanisms and toxicity.
• Analysis of the role of mitochondrial DNA polymerase-γ in NRTI pathogenesis.
• Examination of host factors (e.g., HIV, genetic mutations, sex) influencing toxicity.

Main Results:

• NRTI mitochondrial toxicity is linked to mitochondrial DNA depletion and mutations, affecting cellular respiration.
• The etiology is multifactorial, involving drug interactions, host genetics, and viral factors.
• Current management focuses on NRTI cessation or substitution, with ongoing research into pharmacological interventions.

Conclusions:

• NRTI-induced mitochondrial toxicity is a complex challenge in HIV and HBV therapy.
• Understanding multifactorial etiology is crucial for effective management.
• Developing novel pharmacological treatments and prophylaxes is essential to mitigate NRTI toxicity.