Advisor: Dr. Rudolph L. Gleason, Jr (Georgia Institute of Technology)

Committee Members:
Dr. Robert Guldberg (Georgia Institute of Technology)
Dr. Manu Platt (Georgia Institute of Technology)
Dr. Roy Sutliff (Emory University)
Dr. W. Robert Taylor (Georgia Institute of Technology and Emory University)

Acquired immunodeficiency syndrome (AIDS) is considered a global epidemic with human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, having a worldwide prevalence of over 34 million people. Due to the success of highly active antiretroviral therapy (HAART), HIV-1-infection has been transformed from a terminal diagnosis to a manageable chronic disease. HIV patients, however, have an elevated incidence of dyslipidemia, lipodystrophy, insulin resistance, diabetes mellitus, and cardiovascular disease (CVD); the latter includes an elevated risk of myocardial infarction and higher prevalence of atherosclerotic lesions, as well as increases in markers of subclinical atherosclerosis including increased carotid artery intima-media thickness, increased arterial stiffness  and impaired flow-mediated brachial artery dilation, an indicator of endothelial dysfunction.  Despite the numerous clinical studies, the roles and importance of the HIV-1 virus and the HAART drugs in causing these changes still remains unclear. Discrepancies exist between various studies due to the inability to control other cardiovascular risk factors such as age, gender, weight, cholesterol levels, smoking, and hypertension in all patients as well any confounding effects from different stages of HAART therapy. This study seeks to further investigate the independent roles of the HIV-1 virus and the HAART drug AZT in the development of cardiovascular disease, with emphasis on the development of geometric and biomechanical markers of atherosclerosis.

 Towards this end, in Aim 1 we developed and tested a novel microstructurally-based constitutive model, capable of integrating tissue-level and microstructure biomechanical measurements. In aims 2 and 3 we quantified these biomechanical and microstructure measurements, in parallel with molecular markers of vascular remodeling, in common carotid arteries and aortas in an HIV-1 transgenic mouse model and mice administered the HAART drug AZT.