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 immunity. Design: This was a pilot, open-label, three-arm prospective phase 1 study. Methods: We recruited 28 patients with low plasma vitamin D (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.