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A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection

Lachmann, Raskit and Bevan, Margaret A and Kim, Sangmi and Patel, Nishma and Hawrylowicz, Catherine and Vyakarnam, Annapurna and Peters, Barry S (2015) A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection. In: AIDS, 29 (10). pp. 1127-1135.

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Official URL: http://dx.doi.org/10.1097/QAD.0000000000000666

Abstract

Objectives:To determine if there is a biological mechanism that explains the association between HIV disease progression and increased mortality with low circulating vitamin D levels; specifically, to determine if restoring vitamin D levels induced T-cell functional changes important for antiviral immunity.Design:This was a pilot, open-label, three-arm prospective phase 1 study.Methods:We recruited 28 patients with low plasma vitamin D (<50nmol/l 25-hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment-naive) and 11 healthy controls, who received a single dose of 200000IU oral cholecalciferol. Advanced T-cell flow cytometry methods measured CD4(+) T-cell function associated with viral control in blood samples at baseline and 1-month after vitamin D supplementation.Results:One month of vitamin D supplementation restored plasma levels to sufficiency (>75nmol/l) in 27 of 28 patients, with no safety issues. The most striking change was in HIV+ HAART+ patients, where increased frequencies of antigen-specific T cells expressing macrophage inflammatory protein (MIP)-1 - an important anti-HIV blocking chemokine - were observed, with a concomitant increase in plasma MIP-1, both of which correlated significantly with vitamin D levels. In addition, plasma cathelicidin - a vitamin D response gene with broad antimicrobial activity - was enhanced.Conclusion:Vitamin D supplementation modulates disease-relevant T-cell functions in HIV-infected patients, and may represent a useful adjunct to HAART therapy. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the LIPPINCOTT WILLIAMS & WILKINS, TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
Keywords: cathelicidin; CCL4; CD4(+) T cells; HIV; MIP-1; regulatory T cells; vitamin D
Department/Centre: Division of Biological Sciences > Centre for Infectious Disease Research
Depositing User: Id for Latest eprints
Date Deposited: 17 Feb 2016 07:25
Last Modified: 17 Feb 2016 07:25
URI: http://eprints.iisc.ac.in/id/eprint/53263

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