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 gamma. 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.
BC Centre for Excellence in HIV/AIDS and the Canadian HIV Trials Network, St. Paul's Hospital, Providence Health Care, University of British Columbia, Vancouver, Canada. jmontaner@hivnet.ubc.ca
Julio S G
JS
Montaner
Hélène C F
HC
Côté
Marianne
M
Harris
Robert S
RS
Hogg
Benita
B
Yip
P Richard
PR
Harrigan
Michael V
MV
O'Shaughnessy
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D004272:DNA, Mitochondrial / Q000097:blood*; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D028361:Mitochondrial Diseases / Q000097:blood / Q000139:chemically induced*; D009705:Nucleosides / Q000009:adverse effects*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D009705:Nucleosides; D019344:Lactic Acid