MUSCULOSKELETAL PHYSIOLOGY IN HIV INFECTION

瘦体质量（LBM），特别是肌肉质量的减少，是HIV感染的一个标志，在许多其他疾病和正常衰老中都可以看到。在这些情况下，肌肉减少和免疫能力下降是并行发生的。肌肉质量是力量和功能状态的主要决定因素。锻炼是少数几种可以增加力量（从而提高功能状态）、CD4细胞计数和肌肉量的方法之一。此外，众所周知，运动可以引发感染和其他生理应激后出现的免疫和代谢急性期反应，包括循环白细胞计数升高、外周血单核细胞产生白细胞介素-1增加、蛋白质合成和分解增加、尿中肌肉蛋白排泄增加。这些反应发生在一次剧烈运动之后。因此，免疫系统、身体组成和锻炼之间有着密切的联系。此外，人们还担心急性期反应会诱导HIV的表达。在健康方面，运动导致净蛋白质合成超过蛋白质降解，随后肌肉蛋白质增加。这项提议的总体目标是确定这一过程是否发生在艾滋病毒感染中，以及这种疾病在多大程度上改变了这一过程。本项目提出1)单次大强度运动对急性期反应的影响（横断面研究），以及2)8周渐进式阻力运动干预对身体成分、力量、功能状态、HIV负担和免疫状态的影响（干预研究）。这两项研究将在三组HIV（+）受试者中进行，根据CD4计数和HIV（-）对照进行分类。虽然其中一些研究已经在一些HIV（+）人群中进行，但这是第一次对生理应激和运动的影响进行大规模综合评估，涉及整个HIV（+）受试者和适当的对照。

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.