Weight loss is a common manifestation of patients with acquired immunodeficiency syndrome (AIDS). The wasting syndrome accompanying this disease is multifactorial and is in part due to inadequate food intake and malabsorption, especially in the latter stages of the disease. However, a reduction in lean body mass (LBM) has also been demonstrated prior to changes in caloric intake, suggesting a hypermetabolic catabolic state. The temporal progression as well as the mechanism leading to an erosion of LBM following infection with human immunodeficiency virus (HIV) and the development of AIDS has not been elucidated. The growth hormone (GH)-insulin like growth factor (IGF) axis is thought to be an essential component for protein synthesis and maintenance of LBM in adults. Both GF and IGF-I when administered to humans enhance nitrogen retention and influence muscle protein synthesis. In addition, our laboratories have now defined significant defects in both IGF-I and -II as well as their binding proteins in patients with AIDS who have lost at least 10% of ideal body weight (IBW). The long-term goal of our proposed studies is the systematic assessment of the changes in skeletal muscle protein synthesis and degradation, and the regulatory role of the GH-IGF axis in HIV infected patients. Such investigation will provide a scientific rationale for the appropriate use of nutritional and/or hormonal interventions to prolong survival and enhance the quality of life for patients with AIDS. The working hypothesis to be tested in this proposal is that alterations in the GH-IGF axis resulting from HIV infection impair IGF-I stimulation of anabolic processes, including muscle protein synthesis, and are a contributing factor to the muscle wasting that companies AIDS. To address the questions implicit in this hypothesis, our proposed research has the following specific aims: 1. To quantitate the changes in the rate of skeletal muscle protein synthesis and degradation and the changes in muscle function in HIV+ patients throughout the course of the infection. 2. To document the changes in the GH-IGF axis in HIV+ patients from a period of initial diagnosis of infection through the end stages of AIDS. 3. To determine whether nutritional and GH intervention improve protein retention by influencing muscle metabolism in AIDS patients and to determine at what stage this intervention fails to modulate the IGF system and regulate muscle protein synthesis and breakdown.
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