There is increasing evidence that hypovitaminosis D is common in the general population.~Low dietary intake of vitamin D and reduced exposure to sunlight are probably the major risk factors. A high prevalence of hypovitaminosis D has been described in HIV-infected adults, and children. HIV infection itself and antiretroviral (ARV) treatment may be responsible for alteration of vitamin D metabolism. For instance, studies have shown a significant decrease in serum 25-hydroxyvitamin-D [25(OH)D] concentration in adults receiving non-nucleoside reverse transcriptase inhibitors (NNRTIs). Whatever the cause(s) of hypovitaminosis D, because of the importance of vitamin D in bone health, randomized controlled trials (RCT) have been performed to test whether vitamin D supplementation can improve vitamin D status and bone mineral metabolism in HIV-infected children and adolescents.~Along with its effects on bone metabolism, vitamin D is an important modulator of the immune system. The vitamin D receptor (VDR) is found in high concentrations in activated T lymphocytes, in small amounts in monocyte/macrophage cells while B lymphocytes do not contain detectable amounts of VDR.~Experimental studies have shown that the active di-hydroxylated metabolite of vitamin D [1,25(OH)2D] is able to skew the T cell compartment into a more anti-inflammatory state, with inhibition of Th1 and Th17 cells and promotion of Th2 and T regulatory (Treg) subsets.~In the context of HIV infection, in which Th1 subpopulations are devoted to inhibit viral replication, 16 any alteration of the Th1/Th2 balance would be of concern.~Although all the biological effects of vitamin D are mediated by the 1,25(OH)2D, it is the 25(OH)D to be routinely quantified because of its longer half-life.17 However, HIV-infected subjects may have a defective 1α-hydroxylation of 25(OH)D. Thus, it is important to evaluate the effects of vitamin D supplementation both in terms of 25(OH)D and 1,25(OH)2D responses.~This repeated-measures parallel-group RCT is aimed to test wether a 12-month oral supplementation with cholecalciferol (vitamin D3) is able: 1) to increase serum 25(OH)D and 1,25(OH)2D levels and, 2) to affect T-cell phenotype in vertically HIV-infected children and young adults with hypovitaminosis D and stable HIV-disease.~Main outcome: to determine the frequency of hypovitaminosis D at 12-month of follow-up among subjects supplemented with oral cholecalciferol versus subjects receiving placebo.~Secondary outcome: to investigate correlations - if any - between serum vitamin D concentration and markers of immune activation (i.e. Th1-, Th2-, Th17- and Treg-lymphocytes count, T-lymphocyte VDR expression)
Along with its effects on bone metabolism, vitamin D is an important modulator of the immune system. Experimental studies have shown that the active metabolite of vitamin D [1,25(OH)2D] is able to skew the T cell compartment into a more anti-inflammatory state, with inhibition of Th1 and Th17 cells and promotion of Th2 and T regulatory subsets.~In the context of HIV infection, in which Th1 subpopulations are devoted to inhibit viral replication, any alteration of the Th1/Th2 balance would be of concern.~The aim of this Randomized Controlled Trial is to test wether oral supplementation with cholecalciferol could be able: 1) to improve vitamin D status and, 2) to play an immunomodulatory role, in vertically HIV-infected children and young adults with hypovitaminosis D.