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A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516350/ https://www.ncbi.nlm.nih.gov/pubmed/25870995 http://dx.doi.org/10.1097/QAD.0000000000000666 |
Sumario: | 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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