Vitamin D deficiency is associated with IL-6 levels and monocyte activation in HIV-infected persons

Study to Understand the Natural History of HIV/AIDS in the Era of Effective Antiretroviral Therapy (the 'SUN Study') Investigators

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Background Immune activation plays a key role in HIV pathogenesis. Markers of inflammation have been associated with Vitamin D deficiency in the general population. Studies have also demonstrated associations of Vitamin D deficiency with increased risk of HIV progression and death. The relationship between persistent inflammation and immune activation during chronic HIV infection and Vitamin D deficiency remains unclear. Methods Cryopreserved specimens were analyzed from 663 participants at the time of enrollment from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) from 2004 to 2006. Biomarkers of inflammation, atherosclerosis, and coagulation were measured using enzyme-linked immunosorbent assays (ELISAs) and electrochemiluminescence. 25(OH)D, the stable precursor form of Vitamin D, was measured using a radioimmunoassay with levels defined as: normal (≥30ng/mL), insufficient (20-29 ng/mL) and deficient (<20 ng/mL). Monocyte phenotypes were assessed by flow cytometry. Linear and logistic regression models were used to determine statistical associations between biomarkers and Vitamin D deficiency. Results 25(OH)D levels were deficient in 251 (38%) participants, insufficient in 222 (34%), and normal in 190 (29%). Patients with Vitamin D deficiency, when compared to those with insufficient or normal Vitamin D levels, had increased levels of IL-6 (23%; p<0.01), TNF-α (21%, p = 0.03), D-dimer (24%, p = 0.01), higher proportions of CD14dimCD16+ (22%, p<0.01) and CX3CR1+ monocytes (48%; p<0.001) and decreased frequency of CCR2+ monocytes (-3.4%, p<0.001). In fully adjusted models, Vitamin D associations with abnormal biomarker levels persisted for IL-6 levels and CX3CR1+ and CCR2+ phenotypes. Conclusions Vitamin D deficiency is associated with greater inflammation and activated monocyte phenotypes. The role of Vitamin D deficiency in persistent immune activation and associated complications during chronic HIV disease should be further evaluated as a possible target for intervention.

Original languageEnglish (US)
Article numbere0175517
JournalPloS one
Issue number5
StatePublished - May 2017

Bibliographical note

Funding Information:
This work was supported by the Centers for Disease Control and Prevention contract numbers 200-2002-00610, 200-2002-00611, 200-2002-00612, 200-2002-00613, 200-2007-23633, 200-2007-23634,200-2007-23635, and 200-2007-23636. Additional support was provided by the NIH1KL2RR033182-01. This project has also been funded in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, including the National Institutes of Health and the Centers for Disease and Control and Prevention, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Governmentarticulated in the 'authors contributions' section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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