MUSCULOSKELETAL PHYSIOLOGY IN HIV INFECTION

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Loss of lean body mass (LBM), and specifically muscle mass, is a hallmark of HIV infection and in seen in many other diseases and in normal aging. Decrease in muscle and fall in immune competence occur in parallel in these situations. Muscle mass is a major determinant of strength and of functional status. Exercise is one of the few ways available to increase strength (and thus functional status), and CD4 counts, as well as muscle bulk. In addition, exercise is known to trigger the same kind of immunologic and metabolic acute phase response seen after infections and other physiologic stresses, with elevated circulating white blood cell counts, increased production of interleukin-1Beta by peripheral blood mononuclear cells, elevated protein synthesis and breakdown, and urinary excretion of muscle protein. These responses occur following even a single bout of strenuous exercise. Thus there is an intimate connection between the immune system, body composition, and exercise. Furthermore, concern has been raised that the acute phase response (especially tumor necrosis factor-alpha secretion) can induce expression of HIV. In health, exercise leads to net protein degradation, with subsequent increase in muscle protein. Whether this process occurs in immunologic illness, such as HIV infection, and to what extent it is altered by the disease, remains unknown. This Project proposes to study 1) the effect of a single bout of heavy exercise on the acute phase response. (Cross- Sectional Study), as well as 2) the effect of an eight-week aerobic and resistive exercise intervention on LBM, strength, resting energy expenditure, aerobic capacity, functional status, and immune status (Intervention Study). Both studies will be carried out in three groups of HIV (+) subjects, classified by CD4 count as well as in HIV (-) controls. While some of these studies have been carried out in some groups of HIV (+) people, this is the first large-scale integrated evaluation of the effect of physiologic stress and exercise involving the entire spectrum of HIV (+) subjects and appropriate controls.