Vitamin D functions as a powerful immune modulator and its insufficiency has recently emerged as a risk factor for cardiovascular disease (CVD) and insulin resistance in the general population. Recently, the prevalence of vitamin D insufficiency and deficiency was recognized to be very high in the US pediatric population and low serum vitamin D were found to be strongly and independently associated with hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity or other CVD risk factors. As HIV-infected children are expected to live several decades, issues of long- term toxicities, such as CVD and diabetes become increasingly important in the management of HIV. The central hypothesis of our proposed studies is that, vitamin D deficiency is a risk factor for the development of subclinical atherosclerosis and insulin resistance in HIV infected children/young adults, and that the risk is mediated by changes in systemic inflammation. To strengthen the findings from the observational study, we will conduct an interventional study, in which we hypothesize that high doses of vitamin D given to HIV-infected children/young adults with low vitamin D levels will increase 25-hydroxyvitamin D (25(OH)D) levels at a lower extent than in a matched healthy HIV-negative control group, specifically in patients treated with NNRTI, and will reduce inflammation, insulin resistance and dyslipidemias. Detailed measures of vitamin D pathways will also be determined. The use of vitamin D has the potential to have a significant impact on prevention of HIV cardiovascular and metabolic co-morbidities especially given that the intervention can be implemented easily and inexpensively in clinical practice.

Public Health Relevance

Children living with HIV are surviving through adulthood; however they are suffering from several complications of HIV and its therapy, including increased risk of heart disease and diabetes. Vitamin D can positively modify inflammation, a known risk factor for heart disease and diabetes, and as such has been shown in the general population to improve cardiovascular risk. This study will examine the relationship between vitamin D levels and cardiovascular and metabolic complications and the interplay of inflammation. We will also study the effect of vitamin D supplementation in HIV infected children/youths on cardiac and metabolic morbidities. Lastly, a detailed assessment of the effect of HIV therapies on vitamin D metabolism will be undertaken.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD070490-05
Application #
8898162
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Taylor-Zapata, Perdita
Project Start
2011-08-01
Project End
2017-07-31
Budget Start
2015-08-01
Budget End
2017-07-31
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Eckard, Allison Ross; Raggi, Paolo; O'Riordan, Mary Ann et al. (2018) Effects of vitamin D supplementation on carotid intima-media thickness in HIV-infected youth. Virulence 9:294-305
Eckard, Allison Ross; O'Riordan, Mary Ann; Rosebush, Julia C et al. (2018) Vitamin D supplementation decreases immune activation and exhaustion in HIV-1-infected youth. Antivir Ther 23:315-324
Eckard, Allison Ross; Thierry-Palmer, Myrtle; Silvestrov, Natalia et al. (2017) Effects of cholecalciferol supplementation on serum and urinary vitamin D metabolites and binding protein in HIV-infected youth. J Steroid Biochem Mol Biol 168:38-48
Eckard, Allison Ross; Cho, Soohee; O'Riordan, Mary Ann et al. (2017) Kallistatin levels in HIV-infected patients and effects of statin therapy. Biomarkers 22:55-62
Eckard, Allison Ross; O?Riordan, Mary Ann; Rosebush, Julia C et al. (2017) Effects of Vitamin D Supplementation on Bone Mineral Density and Bone Markers in HIV-Infected Youth. J Acquir Immune Defic Syndr 76:539-546
Ziegler, Thomas R; Judd, Suzanne E; Ruff, Joshua H et al. (2017) Amino Acid Concentrations in HIV-Infected Youth Compared to Healthy Controls and Associations with CD4 Counts and Inflammation. AIDS Res Hum Retroviruses 33:681-689
Hileman, Corrilynn O; Tangpricha, Vin; Sattar, Abdus et al. (2017) Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy. J Acquir Immune Defic Syndr 74:539-547
Eckard, Allison Ross; Raggi, Paolo; Ruff, Joshua H et al. (2017) Arterial stiffness in HIV-infected youth and associations with HIV-related variables. Virulence 8:1265-1273
Eckard, Allison Ross; Meissner, Eric G; Singh, Inderjit et al. (2016) Cardiovascular Disease, Statins, and HIV. J Infect Dis 214 Suppl 2:S83-92
Eckard, Allison Ross; Rosebush, Julia C; Lee, S Thera et al. (2016) Increased Immune Activation and Exhaustion in HIV-infected Youth. Pediatr Infect Dis J 35:e370-e377

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