EXERCISE TESTING AND TRAINING FOR HAART TOXICITY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。接受高效抗逆转录病毒疗法（HAART）治疗HIV感染的患者会受到药物副作用的影响，其中一些可能是由于线粒体毒性。在这项研究中，我们试图确定运动试验是否可以用来识别和量化线粒体毒性，反映在氧化代谢的措施。在前两个方案中，HIV感染的患者将被分为三组：接受HAART的血乳酸正常，接受HAART的血乳酸轻度升高，从未接受HAART。运动试验，测量呼吸气体交换和血液采样以测定乳酸和丙酮酸浓度。将测量身体成分，以表征人群并将运动指标与瘦体重联系起来。我们希望通过运动试验确定一种简便的方法来监测HAART相关的线粒体毒性。在第二个方案中，接受HAART治疗的患者还将接受运动试验和身体成分测量，并且还将进行经皮肌肉活检。然后，他们将被随机分配到运动训练或不训练10周，然后重复所有措施。从这一点上，我们将确定在HAART的设置中，运动训练对全身水平和肌肉细胞水平的氧化功能的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients on highly active antiretroviral therapy (HAART) for HIV infection are subject to side effects of drugs some of which may be due to mitochondrial toxicity. In this study we seek to identify whether exercise testing can be used to identify and quantify mitochondrial toxicity as reflected in measures of oxidative metabolism. In the first two protocols, HIV infected patients will be recruited in three groups: on HAART with normal blood lactate, on HAART with a mildly elevated blood lactate, and never on HAART. Exercise testing with measurement of respiratory gas exchange and blood sampling for determination of lactate and pyruvate concentrations. Body composition will be measured both to characterize the population and for indexing of exercise measures to lean mass. We expect to identify a facile approach to monitoring patients for HAART related mitochondrial toxicity by the use of exercise testing. In the second protocol patients on HAART will also undergo exercise testing and body composition measure, and will also have percutaneous mascle biopsy. They will then be randomized to exercise training or no training for 10 weeks, following which all the measures will be repeated. From this we will define the effects of exercise training on oxidative function at the level of both whole body level and muscle cell in the setting of HAART.