The overall goal of this proposal is to understand the role of inflammatory cytokines in the metabolic and skeletal abnormalities in HIV disease and to determine whether omega-3 fatty acid supplementation, in the form of fish oil, will alter the pathophysiology of these clinical disorders. Complementary and alternative medicines (CAM) are used widely among HIV-infected patients, often with the hope of preventing or treating complications associated with highly active antiretroviral therapy (HAART). Metabolic abnormalities, including peripheral fat wasting, central adiposity, insulin resistance, and dyslipidemia, and skeletal abnormalities (reduced bone mineral density and high bone turnover), are common in HIV-infected patients on HAART, yet their relationship is unclear. We hypothesize that these metabolic and skeletal abnormalities are related by abnormal inflammatory cytokine expression and that these conditions can be improved with fish oil, a widely-used CAM agent with anti-inflammatory properties. We have the following specific aims: 1) To understand the association between the metabolic and skeletal abnormalities in HIV-infected subjects and their relationship to inflammation, 2) To determine whether treatment with omega-3 fatty acids will have hypotriglyeridemic, anti-inflammatory, and anti-bone resorptive effects in a randomized trial of HIV-infected patients, and 3) To clarify the mechanisms of action of omega-3 fatty acids, namely the effect on lipolysis and bone turnover using stable isotope infusion techniques. To accomplish our specific aims, I intend to do a secondary analysis of data from two cohorts of HIV-infected subjects, and to then perform a randomized trial using a standardized fish oil product. These results will help to define the pathophysiology of the metabolic and skeletal abnormalities in HIV and evaluate the efficacy and potential mechanisms of action of an important complementary treatment. This proposal will also help me attain my goal of becoming an independent investigator in the area of CAM and HIV.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AT002862-04
Application #
7447316
Study Section
Special Emphasis Panel (ZAT1-CP (18))
Program Officer
Caldwell, Sheila
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
4
Fiscal Year
2008
Total Cost
$133,510
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Slama, Laurence; Jacobson, Lisa P; Li, Xiuhong et al. (2016) Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men. J Acquir Immune Defic Syndr 71:57-64
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Patil, Susheel P; Brown, Todd T; Jacobson, Lisa P et al. (2014) Sleep disordered breathing, fatigue, and sleepiness in HIV-infected and -uninfected men. PLoS One 9:e99258
Crawford, Keith W; Li, Xiuhong; Xu, Xiaoqiang et al. (2013) Lipodystrophy and inflammation predict later grip strength in HIV-infected men: the MACS Body Composition substudy. AIDS Res Hum Retroviruses 29:1138-45
Metkus, T S; Timpone, J; Leaf, D et al. (2013) Omega-3 fatty acid therapy reduces triglycerides and interleukin-6 in hypertriglyeridemic HIV patients. HIV Med 14:530-9
Monroe, A K; Dobs, A S; Xu, X et al. (2012) Low free testosterone in HIV-infected men is not associated with subclinical cardiovascular disease. HIV Med 13:358-66
Walker Harris, V; Sutcliffe, C G; Araujo, A B et al. (2012) Hip bone geometry in HIV/HCV-co-infected men and healthy controls. Osteoporos Int 23:1779-87
Brown, Todd T; Ross, Allison C; Storer, Norma et al. (2011) Bone turnover, osteoprotegerin/RANKL and inflammation with antiretroviral initiation: tenofovir versus non-tenofovir regimens. Antivir Ther 16:1063-72

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