Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV-infected patients on highly active antiretroviral therapy
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV-infected patients on highly active antiretroviral therapy. / Haugaard, Steen B; Andersen, Ove; Pedersen, Steen B; Dela, Flemming; Richelsen, Bjørn; Nielsen, Jens Ole; Madsbad, Sten; Iversen, Johan; Haugaard, Steen B; Andersen, Ove; Pedersen, Steen B; Dela, Flemming; Richelsen, Bjørn; Nielsen, Jens Ole; Madsbad, Sten; Iversen, Johan.
In: Journal of Medical Virology, Vol. 77, No. 1, 2005, p. 29-38.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV-infected patients on highly active antiretroviral therapy
AU - Haugaard, Steen B
AU - Andersen, Ove
AU - Pedersen, Steen B
AU - Dela, Flemming
AU - Richelsen, Bjørn
AU - Nielsen, Jens Ole
AU - Madsbad, Sten
AU - Iversen, Johan
AU - Haugaard, Steen B
AU - Andersen, Ove
AU - Pedersen, Steen B
AU - Dela, Flemming
AU - Richelsen, Bjørn
AU - Nielsen, Jens Ole
AU - Madsbad, Sten
AU - Iversen, Johan
N1 - 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
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1002/jmv.20410
DO - 10.1002/jmv.20410
M3 - Journal article
C2 - 16032748
VL - 77
SP - 29
EP - 38
JO - Journal of Medical Virology
JF - Journal of Medical Virology
SN - 0146-6615
IS - 1
ER -
ID: 12772156