Abstract
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 language | English (US) |
|---|---|
| Article number | e0175517 |
| Journal | PloS one |
| Volume | 12 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2017 |
Bibliographical note
Funding Information:This research was supported in part by the Intramural Research Program of the NIAID, NIH. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors thank the Membership of the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Antiretroviral (SUN Study) participants and the clinical site investigators and staff. ¶ The investigators of the SUN Study consortium include: Charles Carpenter, Keith Henry, E. Turner Overton, John Hammer, Pragna Patel, and John T. Brooks*. *Lead Author of the SUN Study. E-mail: zud4@cdc.gov . The authors also thank Adam Rupert of Leidos Biomedical Research, Inc. for help with IL-6 and sCD163 measurements. Finally, we would like to acknowledge the work of the late Edie Gunderson, who conducted SUN Study visits in Minneapolis. Edie, loved by staff and participants alike, was known for her boundless energy, dedicated work ethic, and playful demeanor.
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