Journal Article

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

Julio S.G. Montaner, Hélène C.F. Côté, Marianne Harris, Robert S. Hogg, Benita Yip, P. Richard Harrigan and Michael V. O'Shaughnessy

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 38, issue Supplement_2, pages S73-S79
Published in print March 2004 | ISSN: 1058-4838
Published online March 2004 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/381449
Nucleoside-Related Mitochondrial Toxicity among HIV-Infected Patients Receiving Antiretroviral Therapy: Insights from the Evaluation of Venous Lactic Acid and Peripheral Blood Mitochondrial DNA

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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.

Journal Article.  2959 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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