title: A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Vitamin D supplementation modulates disease-relevant T-cell functions in HIV-infected patients, and may represent a useful adjunct to HAART therapy.
authors: aDepartment of Infectious Diseases, King's College London bDivision of Asthma & Allergy, King's College London, London, UK cCentre for Infectious Disease Research, Indian Institute of Science, Bangalore, India. *A. Vyakarnam and B.S. Peters are joint senior authors.
authors: Raskit
authors: R
authors: Lachmann
authors: Margaret A
authors: MA
authors: Bevan
authors: Sangmi
authors: S
authors: Kim
authors: Nishma
authors: N
authors: Patel
authors: Catherine
authors: C
authors: Hawrylowicz
authors: Annapurna
authors: A
authors: Vyakarnam
authors: Barry S
authors: BS
authors: Peters
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D007155:Immunologic Factors; D014807:Vitamin D