The AIDS wasting syndrome (AWS) is a devastating sequela of HIV disease, characterized by the loss of lean body mass out of proportion to weight. Women constitute an increasing percentage of HIV-infected patients--equivalent to 20% of all cases now compared to 8% a decade ago--75% of whom are either African American or Hispanic. Further, evidence suggests that the increasing survival rates seen among men with AIDS have not translated equivalently to women and have not crossed racial lines equally. Despite the recognition that women constitute an ever-expanding population of patients with HIV disease, very little research has been done to develop gender-specific strategies to reverse the wasting syndrome in this population. In preliminary data, the Principal Investigator and his associates demonstrated that the wasting syndrome in women is accompanied by significant loss of muscle mass (sarcopenia) out of proportion to weight which may contribute to decreased survival, decreased overall functional capacity, and reduced quality of life. The mechanism of sarcopenia in women with AWS is not known, but significant evidence suggests the loss of the critical endogenous anabolic factor, testosterone, is a contributing factor. Androgens are known to promote muscle protein synthesis and accrual of lean body mass in other HIV and nonHIV-infected populations of men and women. Further, testosterone administration may improve quality of life, which is shown to correlated with serum androgen levels among HIV-infected women. In effect, the data suggest that androgen deficiency is common in women with AIDS and contributes to decreased lean body mass and overall poor quality of life. Although androgen administration has significant anabolic effects on lean body mass and positive effects on energy and quality of life in nonHIV-infected women, no studies to date have examined the effects of testosterone administration in women with AWS. In the proposed work the Investigator aims to (1) assess the relationship of androgen deficiency and sensitive indices of body cell/fat free mass, energy metabolism, and nutrition in women with AWS, (2) determine the pathophysiologic mechanisms of androgen deficiency in this population, and 3) test the effects of replacing testosterone to physiologic levels vs. placebo therapy on body composition, functional status, and quality of life in a placebo-controlled study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK054167-01
Application #
2654567
Study Section
AIDS and Related Research Study Section 2 (ARRB)
Program Officer
Smith, Philip F
Project Start
1998-05-15
Project End
2003-04-30
Budget Start
1998-05-15
Budget End
1999-04-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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Hadigan, C; Meigs, J B; Corcoran, C et al. (2001) Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 32:130-9

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