title: Mitochondrial interference by anti-HIV drugs: mechanisms beyond Pol-γ inhibition.
abstract: The combined pharmacological approach to the treatment of HIV infection, known as highly active antiretroviral therapy (HAART), has dramatically reduced AIDS-related morbidity and mortality. However, its use has been associated with serious adverse reactions, of which those resulting from mitochondrial dysfunction are particularly widespread. Nucleos(t)ide-reverse transcriptase inhibitors (NRTIs) have long been considered the main source of HAART-related mitochondrial toxicity due to their ability to inhibit Pol-γ, the DNA polymerase responsible for the synthesis of mitochondrial DNA. Nevertheless, accumulating evidence points to a more complex relationship between these organelles and NRTIs. Also, alternative pathways by which other groups of anti-HIV drugs (non-nucleoside reverse transcriptase inhibitors and protease inhibitors) interfere with mitochondria have been suggested, although their implications, both pharmacological and clinical, are open to debate. This review aims to provide a comprehensive overview of the mechanisms and factors which influence the mitochondrial involvement in the toxicity of all three major classes of anti-HIV drugs.
authors: Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Avda Blasco Ibáñez n.15-17, 46010 Valencia, Spain.
authors: Nadezda
authors: N
authors: Apostolova
authors: Ana
authors: A
authors: Blas-García
authors: Juan V
authors: JV
authors: Esplugues
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase