The overall goal of this application is to support the Principal Investigator's efforts in developing a career performing high-caliber patient-oriented research focusing on the metabolic toxicities of antiretroviral therapy. To accomplish this goal, a mentored program of didactic and scientific training is. proposed which includes didactic training through the Clinical Research Scholars Program (CRSP) at Case Western Reserve University (CWRU) and coursework that is part of the Center for Medical Education and Research Development (CMERAD) Program at the Cleveland Clinic Lerner College of Medicine (CCLCM) of CWRU, mentoring and scientific advisory committee consisting of experts in the areas of HIV and metabolic and cardiovascular diseases has been assembled to assist the principal investigator in her efforts to establish a career in patient-oriented research. She will have the full support of the Cleveland Clinic's outstanding research environment. The primary goal of this application is to decrease the morbidity associated with HIV and antiretroviral therapy (ART)-associated metabolic toxicities by evaluating strategies to improve lipoatrophy and subclinical atherosclerosis. To meet these goals, this application has the following specific aims: 1) Evaluate the efficacy of pioglitazone on limb fat and fat mitochondrial DNA in HIV-infected subjects with lipoatrophy treated with thymidine-sparing regimens 2) Evaluate the efficacy of pioglitazone on the metabolic syndrome and underlying atherosclerosis. The hypotheses will be tested using a 48-week prospective, randomized, placebo-controlled trial. Long-term consequences of potent antiretroviral therapy including the metabolic complications of lipodystropohy, insulin resistance and atherosclerotic disease have emerged as a major potential limitation to this life-saving treatment. HIV-related metabolic complications to ART are also likely to have a future increasing global impact as more HIV-infected persons in developing countries gain access to ART.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI070078-04
Application #
7883345
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Brobst, Susan W
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$129,060
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Tungsiripat, Marisa; El-Bejjani, Dalia; Rizk, Nesrine et al. (2012) Changes in Inflammation, Oxidative Stress, Mitochondrial DNA Content after Rosiglitazone in HIV Lipoatrophy. J AIDS Clin Res 3:174
Tungsiripat, Marisa; El-Bejjani, Dalia; Rizk, Nesrine et al. (2011) Carotid intima media thickness, inflammatory markers, and endothelial activation markers in HIV Patients with lipoatrophy increased at 48 weeks regardless of use of rosiglitazone or placebo. AIDS Res Hum Retroviruses 27:295-302
Tungsiripat, Marisa; Bejjani, Dalia El; Rizk, Nesrine et al. (2010) Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens. AIDS 24:1291-8
Tungsiripat, Marisa; Kitch, Douglas; Glesby, Marshall J et al. (2010) A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206. AIDS 24:1781-4
Tungsiripat, Marisa; O'Riordan, Mary Ann; Storer, Norma et al. (2009) Subjective clinical lipoatrophy assessment correlates with DEXA-measured limb fat. HIV Clin Trials 10:314-9
Ross, Allison C; Rizk, Nesrine; O'Riordan, Mary Ann et al. (2009) Relationship between inflammatory markers, endothelial activation markers, and carotid intima-media thickness in HIV-infected patients receiving antiretroviral therapy. Clin Infect Dis 49:1119-27
Tungsiripat, Marisa; McComsey, Grace (2008) Pathogenesis and management of lipoatrophy. Curr HIV/AIDS Rep 5:55-63