The wasting syndrome in AIDS is increasing in prevalence and leading to considerable morbidity and contributing to mortality. Wasting in AIDS was initially thought to be an inevitable consequence of HIV infection. However, data from the laboratory of the investigator and others have suggested that wasting is an intermittent phenomenon induced primarily by secondary illnesses, including systemic infections and gastrointestinal disease. Although there may be periods of weight stability and even weight gain, most patients show incomplete recovery from episodes of weight loss leading to the long term progressive wasting. The specific metabolic changes that cause secondary illnesses to induce weight loss in AIDS are not adequately understood.In addition, the ability of therapy for these secondary illnesses to reverse the metabolic changes, allowing weight gain, has not been properly explored. It is not known whether secondary infection induces increased replication of HIV itself or what the result of increased HIV replication are on energy balance. Finally, the mechanisms by which gastrointestinal disease leads to weight loss are not known. In order to understand the role of secondary illnesses and their treatment in the wasting syndrome of AIDS, the investigator proposes the following specific aims: 1) to determine which components of the energy balance equation, including resting energy expenditure, total energy expenditure and caloric intake, improve with the successful treatment of secondary infections; 2) to determine whether treatment of mycobacterium avium complex results in similar improvements in energy balance since sterilization of bacteria is not always possible; 3) to determine whether opportunistic infections increase HIV viral burden and to determine whether that increase is reversed with treatment of the infection; 4) to determine the effect of HIV viral burden on metabolism; and 5) to determine whether the wasting due to gastrointestinal disease and diarrhea is caused by failed compensatory responses in energy expenditure in the face of decreased food intake. It is the aim of this project, in the determination of the mechanisms of wasting induced by secondary illness, to potentially develop possible new therapeutic approaches in AIDS.
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