This K01 Career Development Award application proposes a multidisciplinary 4-year training program to provide the candidate, Dr. Qibin Qi, with the experience and resources necessary to launch a successful career as an independent investigator. The training plan, developed closely with primary mentor Dr. Kaplan Robert, co-mentor Dr. Kathryn Anastos, and an Advisory Committee, will broaden Dr. Qi's research experience and expertise, including metabolomics, biostatistics and HIV infection and cardiovascular disease (CVD) epidemiology. The proposed research project, building upon two well-characterized HIV cohorts (the Women's Interagency HIV Study [WIHS] and the Multicenter AIDS Cohort Study [MACS]), offers the candidate an outstanding opportunity to become proficient in the novel area of metabolomics research as well as in HIV infection and CVD epidemiology. Taking advantage of archived blood samples, extensive data on HIV-infection related factors, longitudinal measurements of carotid artery plaque, and genomic data in the WIHS and MACS, this project proposes to examine plasma levels of metabolites among 495 women and men, aged = 45 years old, without carotid artery plaque at baseline (338 HIV+ and 157 HIV- subjects; 103 subjects had incident carotid plaque over 7-year follow-up measured by B mode ultrasound). Associations of HIV infection and related factors with prior informed cardiometabolic-associated metabolites (e.g., branched-chain amino acids), and associations between these metabolites and progression of subclinical carotid atherosclerosis (incident carotid artery plaque) will be examined. In exploratory analyses, advance analytical approached (e.g., network analysis) will be applied to identify novel metabolomic signatures related to HIV infection and subclinical atherosclerosis progression, and to generate a network illustrating interrelationships between genes, metabolites, HIV infection and CVD. In addition, potential HIV-specific metabolomic findings will be examined through collaborations with HIV-uninfected population studies. Findings from this study will provide preliminary data for a larger study proposal to measure metabolomics profiling more comprehensively and longitudinally. These studies will advance our understanding of pathogenesis of HIV infection and CVD and provide useful information for effective strategies in the prevention and management of CVD in HIV-infected patients.
With long-term survival of HIV-infected patients (even reaching normal life expectancy) on highly active antiretroviral therapy, CVD has become a leading source of morbidity and mortality. The proposed research project will identify potential biomarkers and targets for individual risk prediction and prevention and holds promise for personalizing antiretroviral therapy medication choice and other interventions to avert CVD among HIV-infected patients.
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