Nucleoside-Related Mitochondrial Toxicity among HIV-Infected Patients Receiving Antiretroviral Therapy: Insights from the Evaluation of Venous Lactic Acid and Peripheral Blood Mitochondrial DNA

Nucleoside analogues inhibit human DNA polymerase γ. As a result, they can produce mitochondrial toxicity. We evaluated the possible role of random venous lactic-acid determinations as a screening tool for mitochondrial toxicity among patients receiving nucleoside therapy. More recently, we have developed an assay that can detect changes in mitochondrial DNA (mtDNA) levels in peripheral blood cells. Using this assay, we have characterized changes in mtDNA relative to nuclear DNA (nDNA) in peripheral blood cells from patients with symptomatic nucleoside-induced hyperlactatemia. Our results demonstrated that symptomatic hyperlactatemia was associated with markedly low mtDNA:nDNA ratios. A statistically significant increase in the mtDNA:nDNA ratio was observed after the discontinuation of antiretroviral therapy. Full validation of monitoring the mtDNA:nDNA ratio is currently under way.