There has been great interest in whether vitamin D supplementation might hold potential for influencing health in aging HIV-infected populations. An estimated 60% of HIV-infected persons have subclinical vitamin D deficiency. Given the established immunomodulatory role of vitamin D as well as its myriad other functions, there is a firm foundation for hypothesizing vitamin D deficiency might have disease risk consequences for older HIV-infected persons. The underlying motivation for this proposal is to use a more comprehensive approach to understanding the complex relationships between vitamin D metabolite levels and inflammation and how they relate to aging outcomes among HIV-infected persons. The proposed study will measure two vitamin D metabolites (25[OH]D and the active form, 1,25[OH]2D), before and after the critical time point of HAART initiation. With these measures, we will capitalize on an existing platform of inflammatory biomarker data in 500 HIV- infected men to study the complex connections between inflammation, vitamin D metabolism and age-related disease. The study includes participants from four study sites across the United States and collaborators from University of Washington and Johns Hopkins University.
The specific aims of this study are: 1) Characterize serum 25[OH] and 1,25[OH]2D levels across strata of age and HIV-status and evaluate the association of each metabolite with available inflammatory markers before and after HAART initiation 2) Determine the association between serum 25[OH] and 1,25[OH]2D levels pre- and post- HAART and both immune reconstitution and chronic disease/geriatric outcomes by age and HIV-status. Understanding how vitamin D metabolism may vary in HIV-infected individuals and impact risk of disease and poor functioning in an aging population is an important issue that will be supported by the proposed epidemiologic research. The biomarkers being evaluated are modifable in terms of their levels in the body and thus have the potential to form the basis of an intervention for lowering risk of disease.

Public Health Relevance

The prevalence of vitamin D deficiency (low serum 25[OH]) is high among HIV-infected individuals and is associated with numerous diseases and morbidities of aging. Little is known, however, about the levels of the active vitamin D metabolite,1,25[OH]2D, in HIV-infected individuals and why supplementation trials have not yielded evidence of benefit. This study will characterize the complex relationship between inflammation and vitamin D metabolism and evaluate the association between vitamin D metabolite levels and disease risk in an aging population of HIV-infected men.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI109817-02
Application #
8780595
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Huebner, Robin E
Project Start
2013-12-01
Project End
2016-11-30
Budget Start
2014-12-01
Budget End
2016-11-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Abraham, Alison G; Zhang, Long; Calkins, Keri et al. (2018) Vitamin D status and immune function reconstitution in HIV-infected men initiating therapy. AIDS 32:1069-1076
Zhang, Long; Tin, Adrienne; Brown, Todd T et al. (2017) Vitamin D Deficiency and Metabolism in HIV-Infected and HIV-Uninfected Men in the Multicenter AIDS Cohort Study. AIDS Res Hum Retroviruses 33:261-270