Abstract

HIV lipodystrophy syndrome is associated with both metabolic (dyslipidemia, insulin resistance) and anthropomorphic (lipoatrophy, central obesity) abnormalities. These defects are likely to predispose HIV patients on highly active antiretroviral therapy (HAART) to accelerated cardiovascular morbidity. On the basis of our data on key mechanisms of altered lipid kinetics in these patients, evidence that diet and exercise patterns of patients with HIV-lipodystrophy are inadequate to manage cardiovascular risk factors, and current recommendations for treatment of atherosclerosis and insulin resistance, we hypothesize that: 1) an intensive lifestyle intervention with diet and exercise will improve the plasma lipid profile, decrease visceral fat mass and improve hormonal, metabolic and lipoprotein markers associated with insulin resistance; and 2) adding niacin, fenofibrate, or a combination of the two drugs to the intensive lifestyle intervention will result in further improvement in the cardiovascular risk profile. We propose a randomized, placebo-controlled clinical trial in 200 hypertriglyceridemic HIV patients on stable HAART treatment with the following Specific Aims: 1) To compare the effects of usual care; intensive diet and exercise (DE); DE + niacin; DE + fenofibrate; and DE + niacin + fenofibrate on fasting plasma lipid concentrations (Primary endpoint); 2) To compare the effects of the five treatment protocols on body fat distribution; 3) To compare the effects of the five treatment protocols on hormonal, lipoprotein and metabolic markers of insulin resistance. Our collaborative team has expertise in lipid and lipoprotein metabolism, innovative and effective diet modification programs, intensive exercise programs in HIV patients, and clinical trials of antilipidemic and antiretroviral agents. Thus, this study will determine the efficacy of diet and exercise, with and without niacin and fenofibrate, in reducing the cardiovascular risk of patients with HIV lipodystrophy / dyslipidemia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL073696-05S2
Application #
7692094
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Mcdonald, Cheryl
Project Start
2003-09-01
Project End
2010-07-31
Budget Start
2007-08-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2008
Total Cost
$46,050
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Misra, Ranjita; Chandra, Prakash; Riechman, Steven E et al. (2013) Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART). BMC Endocr Disord 13:13
Vu, Catherine N; Ruiz-Esponda, Raul; Yang, Eric et al. (2013) Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: further evidence for a unique form of metabolic syndrome in HIV patients. Metabolism 62:1014-20
Gillard, Baiba K; Raya, Joe L; Ruiz-Esponda, Raul et al. (2013) Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function. Arterioscler Thromb Vasc Biol 33:1714-21
Wooten, Joshua S; Nambi, Preethi; Gillard, Baiba K et al. (2013) Intensive lifestyle modification reduces Lp-PLA2 in dyslipidemic HIV/HAART patients. Med Sci Sports Exerc 45:1043-50
Balasubramanyam, Ashok; Coraza, Ivonne; Smith, E O'Brian et al. (2011) Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of ""heart positive,"" a randomized, controlled trial. J Clin Endocrinol Metab 96:2236-47
Nalini, Ramaswami; Ozer, Kerem; Maldonado, Mario et al. (2010) Presence or absence of a known diabetic ketoacidosis precipitant defines distinct syndromes of ""A-?+"" ketosis-prone diabetes based on long-term ?-cell function, human leukocyte antigen class II alleles, and sex predilection. Metabolism 59:1448-55
Sekhar, Rajagopal V; Balasubramanyam, Ashok (2010) Treatment of dyslipidemia in HIV-infected patients. Expert Opin Pharmacother 11:1845-54
Nalini, Ramaswami; Gaur, Lakshmi K; Maldonado, Mario et al. (2008) HLA class II alleles specify phenotypes of ketosis-prone diabetes. Diabetes Care 31:1195-200
Hampe, Christiane S; Nalini, Ramaswami; Maldonado, Mario R et al. (2007) Association of amino-terminal-specific antiglutamate decarboxylase (GAD65) autoantibodies with beta-cell functional reserve and a milder clinical phenotype in patients with GAD65 antibodies and ketosis-prone diabetes mellitus. J Clin Endocrinol Metab 92:462-7
Chang, Evelyn; Sekhar, Rajagopal; Patel, Sanjeet et al. (2007) Dysregulated energy expenditure in HIV-infected patients: a mechanistic review. Clin Infect Dis 44:1509-17

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