The overall scientific goal of this proposal is to determine how host genetic factors relate to adverse effects commonly observed in HIV infection. To achieve this goal, we will analyze DNA samples extracted from participants of a previously established cohort of 327 HIV-infected patients from a large longitudinal study that examines nutritional status in HIV infection. Polymorphisms in the genes commonly linked to metabolic and morphologic abnormalities in the general population will be determined in HIV-positive individuals. Specifically, this proposal aims at examining the association of seven selected candidate genes with incidence and rate of progression of carotid intima-media thickness and coronary calcium scores, and with the presence of metabolic syndrome, all surrogate markers of future cardiovascular events. Finally, dietary intake and individual antiretroviral medications will be assessed for their interaction with candidate genes. We hypothesize that genetic mechanisms confer susceptibility to the development of metabolic and morphologic complications in HIV-infected individuals treated with selective antiretroviral regimens, since these complications do not occur in all exposed patients. This proposal is designed to provide an opportunity for the Principal Investigator (PI) to gain knowledge and skills in designing and conducting clinical and epidemiologic research under the supervision of an advisory committee comprised of highly qualified mentors in an environment ideally suited for the study of HIV disease and genetic analysis. Through coursework, seminars and supervised research, the PI will gain knowledge and expertise in techniques pertinent to the proposed research. This K23 award in combination with the PI's background in infectious diseases, nutrition, clinical epidemiology and biostatistics, will provides excellent potential for the development of a successful independent research career focused on patient-oriented research in the genetic epidemiology of complications in HIV infection. At the end of the award, the PI will be a competitive applicant for R01 funding. PUBLIC HEALTH IMPLICATIONS: The proposed study has significant clinical and public health implications as the results may affect the choice of future antiretroviral medications, dietary interventions, risk stratification guidelines and preventive strategies to avoid the metabolic and morphologic complications observed with HIV disease and its treatment, and may lead to directed interventions in the care of patients.

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 #
5K23AI071872-05
Application #
7880146
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Mckaig, Rosemary G
Project Start
2006-07-01
Project End
2011-01-31
Budget Start
2010-06-01
Budget End
2011-01-31
Support Year
5
Fiscal Year
2010
Total Cost
$122,814
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Mangili, Alexandra; Ahmad, Raabia; Wolfert, Robert L et al. (2014) Lipoprotein-associated phospholipase A2, a novel cardiovascular inflammatory marker, in HIV-infected patients. Clin Infect Dis 58:893-900
Volpe, Gretchen E; Wanke, Christine A; Imai, Cindy M et al. (2014) High-fat meals do not impair postprandial endothelial function in HIV-infected and uninfected men. AIDS Res Hum Retroviruses 30:881-7
Mangili, Alexandra; Polak, Joseph F; Quach, Lien A et al. (2011) Markers of atherosclerosis and inflammation and mortality in patients with HIV infection. Atherosclerosis 214:468-73