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A Comparative Phase 1 Clinical Trial to Identify Anti-infective Mechanisms of Vitamin D in People With HIV Infection

Lachmann et al., AIDS (2015) - PMID: 25870995

Product(s) used in this publication: PepMix™ Peptide Pools

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 (<50 nmol/l 25-hydroxyvitamin D3), comprising 17 HIV+ patients (11 on HAART, six treatment-naive) and 11 healthy controls, who received a single dose of 200 000 IU 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 (>75 nmol/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)-1β - an important anti-HIV blocking chemokine - were observed, with a concomitant increase in plasma MIP-1β, 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.

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