The overall aims of this five-year career development award are to 1.) enable the candidate's career development as an independent clinical researcher through advanced didactic coursework, structured mentoring and conduct/analysis of a clinical research study;and 2.) better define vitamin D status as a mediator of HIV-related cardiovascular disease (CVD) as well as to determine if vitamin D status changes the effect of rosuvastatin on HIV-related CVD risk. Adults living with HIV are at higher risk than the general population for CVD. Vitamin D deficiency is common in HIV, and appears to play a critical role in systemic inflammation and CVD in the general population, but is not well studied in HIV. Strategies to modify the risk of CVD in HIV present an opportunity for primary disease prevention-an important public health alternative to the treatment of established disease and closely aligned with the mission of NHLBI "to promote the prevention and treatment of heart disease and enhance the health of all individuals so that they can live longer and more fulfilling lives." The candidate will conduct two separate, but complimentary studies one ambispective, cohort study and one randomized clinical trial that will be embedded into two already funded, ongoing studies.
The specific aims of the candidates proposal are: 1.) to evaluate the effect over time of vitamin D status on carotid intima media thickness (cIMT) progression and proinflammatory biomarkers in HIV- infected adults before and after initiating antiretroviral therapy (ART) and in age-, sex- and race-matched HIV- uninfected adults;2.) to evaluate the impact over time of rosuvastatin on vitamin D levels in HIV-infected adults on stable ART;and 3.) to determine if vitamin D status modifies the effect of rosuvastatin on surrogate markers of CVD, proinflammatory biomarkers and cholesterol levels in HIV-infected adults on stable ART. Endpoints will include established surrogate markers of CVD, i.e., cIMT measured by ultrasound, coronary artery calcium score measured by CT scanning, flow mediated dilation of the brachial artery measured by ultrasound, and several important biomarkers of inflammation, endothelial activation, coagulation and oxidation. Statistical analyses will include multiple linea regression and mixed effects modeling. The candidate will be mentored by a multidisciplinary team led by Dr. Grace McComsey, an internationally-recognized clinical researcher in HIV- related metabolic complications, including cardiovascular disease. The candidate has shown a dedication to a career in clinical research through receipt of a Master's in Epidemiology and profile of research projects to date focused in the area of HIV-related CVD and targets to ameliorate this risk. This Career Development Award will provide the foundation for the candidate to pursue an independent research career dedicated to better understanding the pathophysiology of and targets to reduce subsequent morbidity and mortality associated with HIV-related CVD.

Public Health Relevance

- People living with HIV are now suffering from several complications of HIV and its treatment including heart disease. Vitamin D deficiency is common in HIV and has been linked to cardiovascular disease in the general population but has not been well studied in HIV. A better understanding of the association between vitamin D deficiency and cardiovascular disease risk in HIV will provide insight for future clinical trials specifically targeting vitamin D deficiency with the goal of reducing morbidity and mortality due to heart disease in HIV.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL116209-02
Application #
8704999
Study Section
Special Emphasis Panel (ZHL1-CSR-X (O1))
Program Officer
Scott, Jane
Project Start
2013-07-22
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$133,431
Indirect Cost
$8,931
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Hileman, Corrilynn O; Labbato, Danielle E; Storer, Norma J et al. (2014) Is bone loss linked to chronic inflammation in antiretroviral-naive HIV-infected adults? A 48-week matched cohort study. AIDS 28:1759-67
Longenecker, Chris T; Hileman, Corrilynn O; Funderburg, Nicholas T et al. (2014) Rosuvastatin preserves renal function and lowers cystatin C in HIV-infected subjects on antiretroviral therapy: the SATURN-HIV trial. Clin Infect Dis 59:1148-56