Antiretroviral Nucleoside and Nucleotide Analogues and Mitochondria

The 2004 document reviews the effects of antiretroviral nucleoside and nucleotide analogues (NRTIs) on mitochondrial DNA (mtDNA) and function, with a focus on HIV treatment. It emphasizes the importance of precise mtDNA measurement in human cells, considering cell type variability and potential sample contamination. The paper associates NRTIs with adverse events like lactic acidosis and peripheral neuropathy, which are thought to stem from mitochondrial dysfunction, but also notes that these conditions can have multiple causes. A retrospective study in France found a 0.46% incidence of suspected mitochondrial dysfunction in infants exposed to NRTIs in utero, contrasting with a larger US study that found no similar deaths among over 20,000 children. The document suggests that HIV infection may increase mitochondrial vulnerability to NRTI toxicity and discusses genetic factors that could affect individual susceptibility to this toxicity.