Correlation of increases in 1,25-dihydroxyvitamin D during vitamin D therapy with activation of CD4+ T lymphocytes in HIV-1-infected males.

Background: In HIV-1-infected individuals, levels of CD4+ T lymphocytes are depleted and regulatory T-lymphocytes (Tregs) are elevated. In vitro studies have demonstrated effects of vitamin Don the growth and differentiation of these cells. We speculated whether supplementation with vitamin D could have an effect on CD4+ T lymphocytes or Tregs in HIV-1-infected males. Methods: We conducted a placebo-controlled randomized study that ran for 16 weeks and included 61 HIV-1-infected males, of whom 51 completed the protocol. The participants were randomized to 1 of 3 daily treatments: (1) 0.5-1.0 mu g calcitriol and 1200 IU (30 mu g) cholecalciferol, (2) 1200 IU cholecalciferol, (3) placebo. Percentages of the following T-lymphocyte subsets were determined: naive CD4+ and CD8+ cells, activated CD4+ and CD8+ cells, and CD3+CD4+CD25+CD127(low) Tregs. Furthermore 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone were measured. Results: No significant changes of the studied T-lymphocyte subsets occurred in the treatment groups compared to the placebo group. Increases in 1,25-dihydroxyvitamin D were associated with increases in activated CD4+ T lymphocytes (P = .001) and Tregs (P = .01) in adjusted models. Changes in parathyroid hormone correlated inversely with Tregs (P = .02). Smokers had higher levels of naive CD4+ T lymphocytes (37% vs 25%; P = .01), naive CD8+ T lymphocytes (28% vs 19%; P = .03), and Tregs (9% vs 7%; P = .03). Conclusion: Cholecalciferol and calcitriol administered during 16 weeks did not change the levels of T-lymphocyte fractions compared to placebo. However, increases in 1,25-dihydroxyvitamin D were associated with an expansion of activated CD4+ cells and Tregs.