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.
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