Abnormalities of body morphology consisting of central obesity and peripheral-lipoatrophy, often associated with metabolic abnormalities of insulin resistance and hyperlipidemia, have been increasingly reported in the HIV infected population coincident with the widespread use of highly active anti-retroviral therapy [HAART]. The pathophysiologic mechanisms underlying the development of these abnormalities are poorly understood. An intriguing possibility is that there may be a subset of HIV-infect patients who are at risk for this metabolic syndrome independent of HIV, and that the HIV infection results in the emergence of the phenotype characteristic of this syndrome. This study will explore the clinical benefit and short term safety of testosterone in minimizing and potentially reversing the changes of HIV associated lipodystrophy and metabolic dysfunction and explore the possible pathophysiologic mechanisms underlying these abnormalities. The study will be conducted as a double blind, randomized 6 month trial of testosterone versus placebo in HIV infected individuals with lipodystrophy who have evidence of reasonably controlled HIV infection on HAART and who are hypogonadal or have plasma total testosterone levels in the lower half of the normal range for men. Changes in lipodystrophy will be assessed by standard anthropometric measurements as well as by dual energy X-ray absorptiometry [DEXA] and quantitative CT scans of the abdomen at the level of the umbilicus, mid-chest and mid-thigh. The utility of anthropometric techniques will be compared to measures as obtained by DEXA and CT. Insulin resistance will be evaluated with the use of frequently sampled intravenous glucose tolerance test [FSIGT]. Post- heparin lipoprotein lipase (PH-LPL) and hepatic lipase (HL) activity will be determined. The role of macrophages will be assessed by the determination of macrophage LPL and TNFalpha mRNA expression in isolated peripheral blood monocytes and adipose tissue macrophages. Adipose tissue from the anterior abdomen will be examined histologically and for mRNA expression of adipose LPL, TNFalpha, macrophage colony stimulating factor and PPAR-gamma. Adipose samples will also be stored at -70C for future analysis of potential gene markers.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54RR014607-03
Application #
6496379
Study Section
Special Emphasis Panel (ZRR1)
Project Start
2001-09-01
Project End
2002-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
2001
Total Cost
$173,158
Indirect Cost
Name
University of Hawaii
Department
Type
DUNS #
121911077
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Riangwiwat, Tanawan; Kohorn, Lindsay B; Chow, Dominic C et al. (2016) CD4/CD8 Ratio Predicts Peripheral Fat in HIV-Infected Population. J Acquir Immune Defic Syndr 72:e17-9
Wright, Tricia E; Schuetter, Renee; Tellei, Jacqueline et al. (2015) Methamphetamines and pregnancy outcomes. J Addict Med 9:111-7
Burlingame, J; Horiuchi, B; Ohana, P et al. (2012) The contribution of heart disease to pregnancy-related mortality according to the pregnancy mortality surveillance system. J Perinatol 32:163-9
Horton, J S; Yamamoto, S Y; Bryant-Greenwood, G D (2012) Relaxin augments the inflammatory IL6 response in the choriodecidua. Placenta 33:399-407
Hiraoka, Mark; Urschitz, Johann; Sultan, Omar et al. (2011) A polymorphism in the retinol binding protein 4 gene is not associated with gestational diabetes mellitus in several different ethnic groups. Hawaii Med J 70:164-7
Horton, J S; Yamamoto, S Y; Bryant-Greenwood, G D (2011) Relaxin modulates proinflammatory cytokine secretion from human decidual macrophages. Biol Reprod 85:788-97
Wright, T E; Milam, K A; Rougee, L et al. (2011) Agreement of umbilical cord drug and cotinine levels with maternal self-report of drug use and smoking during pregnancy. J Perinatol 31:324-9
Kendal-Wright, C E; Hubbard, D; Gowin-Brown, J et al. (2010) Stretch and inflammation-induced Pre-B cell colony-enhancing factor (PBEF/Visfatin) and Interleukin-8 in amniotic epithelial cells. Placenta 31:665-74
Urschitz, Johann; Kawasumi, Miyuri; Owens, Jesse et al. (2010) Helper-independent piggyBac plasmids for gene delivery approaches: strategies for avoiding potential genotoxic effects. Proc Natl Acad Sci U S A 107:8117-22
Wright, Tricia E; Tam, Elizabeth (2010) Disparate rates of persistent smoking and drug use during pregnancy of women of Hawaiian ancestry. Ethn Dis 20:S1-215-8

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