Methods: Vitamin D metabolites (25-hydroxy vitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [ 1,25(OH)2D] ) were quantified, and 17 inflammatory markers were centrally measured from stored serum using multiplex assays. Exploratory factor analysis (EFA) was applied to identify underlying inflammatory processes. Multivariate generalized estimating equations were used to evaluate the relationship between different inflammatory processes and vitamin D metabolites 25(OH)D and 1,25(OH)2D and vitamin D deficiency, defined as 25(OH)D < 20 ng/mL.
Results: A total of 1081 study visits from 610 HIV+ and 97 HIV- men were included, and 66% of HIV+ study visits were on HAART treatment. Compared to HIV- men, HIV+ men had comparable median levels of 25(OH)D (23 ng/mL vs 21 ng/mL) and 1,25(OH)2D (45 pg/mL vs 47 pg/mL), and the prevalence of vitamin D deficiency was 40% in HIV+ and 46% in HIV- men. EFA identified three underlying inflammatory processes: factor 1, characterized by sTNF receptor-2, sIL-2 receptor-a, sCD27, B-cell activating factor, IFN-γ-p10, TNF-a, sCD14, sIL-6 receptor and sGP130; factor 2, characterized by IL-8, GM-CSF, IL-6, IL-1-β, IL-2, MIP-1; factor 3, characterized by IL-10 and IL-12-p70. Factor 1 was significantly associated with a lower odds of vitamin D deficiency (OR=0.78) and lower levels of 1,25(OH)2D (estimate=-2.44 pg/mL per one SD of factor 1 increase) in HIV+ men, and factor 2 was significantly associated with lower levels of 25(OH)D in HIV+ men. Similar but non-significant associations of factor 1 and factor 2 with vitamin D metabolites were found in HIV- men. Factor 3 was not a significantly predictor in either group.
Conclusion: HIV-associated inflammatory factor 1 was correlated with higher levels of 25(OH)D but lower levels of 1,25(OH)2D, and factor 2 was correlated with lower levels of 25(OH)D, which may indicate a pathway whereby HIV-associated microbial translocation and immune activation contribute to elevated risk of comorbidities in HIV-infected men.
J. Margolick, None
M. Witt, NIH: Grant Investigator , Research grant
Gilead Sciences: Scientific Advisor , Research grant and Salary
F. Palella Jr., None
L. Kingsley, None
A. Hoofnagle, Waters, Inc.: Grant Investigator , Research grant
A. Tin, None
L. Jacobson, None
A. Abraham, None