calcitriol and HIV-Infections

Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH). Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH). TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health.. NCT01751646 (ATN 109) and NCT01769469 (ATN 117).

Topics: Adolescent; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Black or African American; Bone and Bones; Bone Density; Cohort Studies; Emtricitabine; Female; HIV; HIV Infections; Humans; Male; Parathyroid Hormone; Pre-Exposure Prophylaxis; Tenofovir; Vitamin D; Vitamin D Deficiency; White People; Young Adult

HIV-1-infected patients have an increased risk of osteoporosis and fractures. The main objective of this study was to evaluate the bone metabolism in HIV-1-infected patients exposed to calcitriol and cholecalciferol. We also investigated the relationship between T cells and bone markers. We conducted a placebo-controlled randomized study running for 16 weeks including 61 HIV-1-infected males, of whom 51 completed the protocol. Nineteen participants were randomized to daily treatment with (A) 0.5-1.0 μg calcitriol and 1,200 IU (30 μg) cholecalciferol, 17 participants to (B) 1,200 IU cholecalciferol, and 15 participants to (C) placebo. At baseline and after 16 weeks, we determined collagen type 1 trimeric cross-linked peptide (CTx), procollagen type 1 N-terminal peptide (P1NP), parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. We determined naive CD4(+) and CD8(+), activated CD4(+) and CD8(+), and regulatory CD4(+)CD25(+)CD127(low) T lymphocytes. Baseline levels of P1NP and CTx correlated (coefficient 0.5, p<0.001) with each other but not with PTH, 25OHD, or 1,25(OH)2D. In patients receiving calcitriol and cholecalciferol, the mean levels of P1NP (p<0.001) and CTx (p= 0.002) declined significantly compared to our placebo group. Based on changes in P1NP and CTx, we estimated that net bone formation occurred more frequently in group A compared to groups B and C. PTH correlated inversely with naive CD4(+) and CD8(+) cells. Otherwise, no relationships between bone markers and T lymphocytes were demonstrated. Supplementation with calcitriol and cholecalciferol induced biochemical indications of bone formation in HIV-1 patients.

Topics: Adult; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Calcitriol; Calcium; Cholecalciferol; Collagen Type I; Double-Blind Method; HIV Infections; HIV-1; Humans; Male; Middle Aged; Osteogenesis; Parathyroid Hormone; Peptide Fragments; Peptides; Procollagen; Prospective Studies; T-Lymphocyte Subsets; Vitamin D

The best repletion and maintenance dosing regimens with cholecalciferol in vitamin D-deficient HIV-1 patients remain unknown. Protease inhibitors (PIs) have been shown to inhibit vitamin D 1α- and 25α-hydroxylation in hepatocyte and monocyte cultures. We therefore evaluated the effect of a single high dose of cholecalciferol in vitamin D-deficient HIV-1 postmenopausal women undergoing treatment with highly active anti-retroviral therapy (cART), with and without PIs. Forty HIV-1 postmenopausal women treated with cART, with hypovitaminosis D (<20 ng/ml), were enrolled. We measured serum changes of 25-hydroxyvitamin D [25(OH)D]; 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), serum calcium, and urinary calcium excretion following a loading dose of 600,000 IU of cholecalciferol after 3, 30, 60, 90, and 120 days. Patients were divided into two groups, whether or not they were taking PI. A significant increase in mean 25(OH)D and 1,25(OH)2D levels at day 3 and throughout the entire observation period was found in both groups (p < 0.001). PTH levels concomitantly decreased in both groups (p < 0.001). Mean albumin-adjusted serum calcium increases with respect to baseline were significant only at day 3 and day 30 for both groups (p < 0.01). Considering remaining parameters, there were no significant differences between the groups at any time, by two-way RM ANOVA. An oral dose of 600,000 IU of cholecalciferol in HIV-1 postmenopausal women rapidly increases 25(OH)D and 1,25(OH)2D levels reducing PTH levels, regardless of the presence of PIs in the cART scheme.

Topics: Cholecalciferol; Female; HIV Infections; Humans; Parathyroid Hormone; Pilot Projects; Postmenopause; Protease Inhibitors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen-presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] can directly affect the proliferation and function of human naturally occurring Treg cells in vitro. First, we demonstrated that these Treg cells express vitamin D receptors that were up-regulated following anti-CD3/CD28-bead stimulation. 1,25(OH)2D3 inhibited proliferation of Treg cells even when exogenous interleukin-2 was provided. Treg cells were more susceptible to the inhibitory effect of 1,25(OH)2D3 than conventional T cells(.) 1,25(OH)2D3 neither affected the anergic state nor the suppressive function of Treg cells but induced a subtle increase in interleukin-10-secreting cells. The cell-division-inhibiting effect of 1,25(OH)2D3 on Treg cells was also demonstrated in vivo by supplementing vitamin D-deficient HIV-1-infected patients with 2000 IU cholecalciferol (vitamin D3). Increased serum 1,25(OH)2D3 levels were associated with a drop in the number and percentage of Treg cells, which may be attributed to a decrease in the proliferating Foxp3+ Treg cell population. In conclusion, 1,25(OH)2D3 directly affects Treg cell growth and promotes interleukin-10 production without apparent effects on activation status and suppressive phenotype whereas in vivo, high serum 1,25(OH)2D3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells.

Topics: Antigen Presentation; Antigen-Presenting Cells; Cell Proliferation; Cells, Cultured; HIV Infections; Humans; Interleukin-10; Interleukin-2; Lymphocyte Activation; Receptors, Calcitriol; T-Lymphocytes, Regulatory; Vitamin D; Vitamin D Deficiency