Loss of lean body mass (LBM), and specifically muscle mass, is a hallmark of HIV infection and is seen in many other disease 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 interlukin-1 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 can induce expression of HIV. In health, exercise leads to net protein synthesis in excess of protein degradation, with subsequent increase in muscle protein. The broad objective of this proposal is to determine whether this process occurs in HIV infection, and to what extent it is altered by the disease. This project proposes 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 progressive resistance exercise intervention on body composition, strength, functional status, HIV burden, 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.
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