Casula M, van der Valk M, Wit F W, Nievaard M A, Reiss P
International Antiviral Therapy Evaluation Centre, Pietersbergweg 8, 1105 BM Amsterdam, The Netherlands.
HIV Med. 2007 Jan;8(1):32-7. doi: 10.1111/j.1468-1293.2007.00428.x.
Several studies have compared mitochondrial DNA (mtDNA) content in tissue from HIV-1-infected patients on highly active antiretroviral therapy with and without evidence of lipodystrophy, the diagnosis of which was based on subjective clinical assessment.
The aim of this study was to assess the utility of mtDNA quantification as a marker of HIV-associated lipodystrophy as diagnosed using a published validated case definition.
We assessed mtDNA content in adipocytes from both thigh and lumbar subcutaneous adipose tissue (n=19), and in peripheral blood mononuclear cells (PBMC) (n=26), obtained from 26 HIV-1-infected patients classified as having lipodystrophy (n=17) or not having lipodystrophy (n=9) according to the validated definition derived from the Lipodystrophy Case Definition Study.
The adipocyte and PBMC mtDNA contents did not significantly differ between patients with and without lipodystrophy. Lipodystrophy patients had been treated for significantly longer times, especially with dideoxynucleoside analogues. In both groups, the thigh adipocyte mtDNA content was significantly greater than that of the lumbar region. When all patients were considered together, a statistically significant negative correlation was found between thigh adipocyte mtDNA content and stavudine treatment duration.
Longer exposure to dideoxynucleoside analogues was associated with lipodystrophy, and longer exposure to stavudine was correlated with lower mtDNA content in thigh adipocytes. However, a single measurement of adipocyte mtDNA content in this limited sample of patients could not distinguish between patients with and without clinical lipodystrophy. The observed variation in mtDNA content between different subcutaneous adipose tissue depots argues for harmonization of future studies regarding which depot to biopsy.
多项研究比较了接受高效抗逆转录病毒治疗的HIV-1感染患者组织中的线粒体DNA(mtDNA)含量,这些患者有或没有脂肪代谢障碍的证据,脂肪代谢障碍的诊断基于主观临床评估。
本研究的目的是评估使用已发表的经过验证的病例定义诊断的mtDNA定量作为HIV相关脂肪代谢障碍标志物的效用。
我们评估了从26名HIV-1感染患者获得的大腿和腰部皮下脂肪组织(n = 19)中的脂肪细胞以及外周血单核细胞(PBMC)(n = 26)中的mtDNA含量,这些患者根据脂肪代谢障碍病例定义研究得出的经过验证的定义被分类为患有脂肪代谢障碍(n = 17)或没有脂肪代谢障碍(n = 9)。
有脂肪代谢障碍和没有脂肪代谢障碍的患者之间,脂肪细胞和PBMC的mtDNA含量没有显著差异。脂肪代谢障碍患者的治疗时间明显更长,尤其是使用双脱氧核苷类似物治疗的时间。在两组中,大腿脂肪细胞的mtDNA含量均显著高于腰部。当将所有患者综合考虑时,发现大腿脂肪细胞mtDNA含量与司他夫定治疗持续时间之间存在统计学上的显著负相关。
更长时间暴露于双脱氧核苷类似物与脂肪代谢障碍有关,更长时间暴露于司他夫定与大腿脂肪细胞中较低的mtDNA含量相关。然而,在这个有限的患者样本中对脂肪细胞mtDNA含量进行单次测量无法区分有临床脂肪代谢障碍和没有临床脂肪代谢障碍的患者。不同皮下脂肪组织部位之间观察到的mtDNA含量差异表明,未来关于活检哪个部位的研究需要统一。