@article{94091b605f2f11dea8de000ea68e967b,
title = "Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV-infected patients on highly active antiretroviral therapy",
abstract = "The nucleoside reverse transcriptase inhibitors (NRTIs), especially stavudine, may deplete mitochondrial (mt) DNA in human tissues by inhibiting the mitochondrial polymerase gamma, a setting, which is associated with hyperlactatemia. The aim of the present study was to examine whether hyperlactatemia is associated with depletion of skeletal muscle (sm)-mtDNA and decreased oxidative capacity in HIV-infected patients on NRTI based highly active antiretroviral therapy (HAART) and whether HIV infection itself is associated with sm-mtDNA depletion. Sm-mtDNA was determined in 42 HIV-infected patients (35 patients on HAART including at least one NRTI (HIV-NRTI) and 7 patients never treated with antiretroviral drugs (NAIVE)) and 14 healthy controls. Whole body oxidative capacity (DeltaGOX) was estimated in HIV-infected patients by indirect calorimetry. Hyperlactatemia (>or=2.0 mM) was detected in six HIV-NRTI, who all used Stavudine (P < 0.01), displayed depleted sm-mtDNA (P < 0.02) and decreased DeltaGOX (P < 0.01) compared with normolactatemic HIV-NRTI (n = 29). NAIVE displayed decreased sm-mtDNA (P < 0.05), increased HIV-RNA (P < 0.01) and increased plasma TNF-alpha (P < 0.05) compared to all HIV-NRTI (n = 35), in turn displaying decreased sm-mtDNA (P < 0.01) compared to healthy controls. Thus, hyperlactatemia in HIV-NRTI may be associated with pronounced depletion of sm-mtDNA, decreased oxidative capacity and current stavudine therapy. Further, HIV may deplete sm-mtDNA of NAIVE, which in part could be mediated through an enhanced pro-inflammatory response.",
author = "Haugaard, {Steen B} and Ove Andersen and Pedersen, {Steen B} and Flemming Dela and Bj{\o}rn Richelsen and Nielsen, {Jens Ole} and Sten Madsbad and Johan Iversen and Haugaard, {Steen B} and Ove Andersen and Pedersen, {Steen B} and Flemming Dela and Bj{\o}rn Richelsen and Nielsen, {Jens Ole} and Sten Madsbad and Johan Iversen",
note = "Keywords: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; DNA, Mitochondrial; Gene Deletion; HIV Infections; Humans; Lactic Acid; Middle Aged; Mitochondrial Diseases; Muscle, Skeletal; Oxidation-Reduction",
year = "2005",
doi = "10.1002/jmv.20410",
language = "English",
volume = "77",
pages = "29--38",
journal = "Journal of Medical Virology",
issn = "0146-6615",
publisher = "JohnWiley & Sons, Inc.",
number = "1",
}
