دورية
Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV‐infected patients on highly active antiretroviral therapy
| العنوان: | Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV‐infected patients on highly active antiretroviral therapy |
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| المؤلفون: | Haugaard, Steen B., Andersen, Ove, Pedersen, Steen B., Dela, Flemming, Richelsen, Bjørn, Nielsen, Jens Ole, Madsbad, Sten, Iversen, Johan |
| المصدر: | Journal of Medical Virology; September 2005, Vol. 77 Issue: 1 p29-38, 10p |
| مستخلص: | 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 (NAÏVE)) and 14 healthy controls. Whole body oxidative capacity (ΔGOX) was estimated in HIV‐infected patients by indirect calorimetry. Hyperlactatemia (≥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 ΔGOX (P< 0.01) compared with normolactatemic HIV‐NRTI (n = 29). NAÏVE displayed decreased sm‐mtDNA (P< 0.05), increased HIV‐RNA (P< 0.01) and increased plasma TNF‐α (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 NAÏVE, which in part could be mediated through an enhanced pro‐inflammatory response. J. Med. Virol. 77:29–38, 2005. © 2005 Wiley‐Liss, Inc. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 01466615 10969071 |
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| DOI: | 10.1002/jmv.20410 |