Effects of cholecalciferol supplementation on serum and urinary vitamin D metabolites and binding protein in HIV-infected youth

Abstract

Vitamin D insufficiency is widespread in HIV-infected patients. HIV and/or antiretroviral therapy (ART), particularly efavirenz (EFV), may interfere with vitamin D metabolism. However, few data from randomized, controlled trials exist. Here, we investigate changes in vitamin D metabolites and binding protein (VDBP) after 6 months of supplementation in a randomized, active-control, double-blind trial investigating 2 different monthly cholecalciferol (vitamin D3) doses [60,000 (medium) or 120,000 (high) IU/month] vs. a control arm of 18,000 IU/month in 8–25 year old HIV-infected youth on ART with HIV-1 RNA <1000 copies/mL and baseline 25-hydroxycholecalciferol (25(OH)D3) ≤30 ng/mL. A matched healthy uninfected group was enrolled in a similar parallel study for comparison. Changes after 6 months were analyzed as intent-to-treat within/between groups [control group (low dose) vs. combined supplementation doses (medium+high)]. At 6 months, 55% vs. 82% of subjects in control and supplementation groups, respectively, reached 25(OH)D3 ≥30 ng/mL (P=0.01) with no difference between medium and high doses (both 82% ≥30 ng/mL). There were few differences for those on EFV vs. no-EFV, except serum VDBP decreased in EFV-treated subjects (both within- and between-groups P≤0.01). There were no significant differences between the HIV-infected vs. healthy uninfected groups. The major finding of the present study is that cholecalciferol supplementation (60,000 or 120,000 IU/month) effectively raises serum 25(OH)D3 in the majority of HIV-infected subjects, regardless of EFV use. Notably, response to supplementation was similar to that of uninfected subjects.

Continued Interest and Controversy: Vitamin D in HIV

“…Several recent trials have explored the ability of VitD supplementation to improve bone-related outcomes among HIV-infected individuals. Dosing approaches have ranged from daily supplements (4000–7000IU) to intermittent high dose boluses (16,000IU weekly to 200,000 x one time) [53–56]. Most studies have utilized cholecalciferol (VitD 3 ) supplements, however protocols employing ergocalciferol (VitD 2 ) and one using calcidiol have also been reported.…”

A Randomized Placebo-Controlled Trial of Low- Versus Moderate-Dose Vitamin D3 Supplementation on Bone Mineral Density in Postmenopausal Women With HIV

“…20 In U.S. children and young adults with serum 25-OHD concentrations below 30 ng/ml, Eckhard et al found that monthly supplementation with 18,000 IU of VitD resulted in serum 25-OHD concentrations above 30 ng/ml in 82% of participants, with similar increases observed amongst people with HIV and uninfected controls. 22 A major focus of VitD supplementation studies in persons with HIV has been to address musculoskeletal complications, such as bone loss and fractures; however, the clinical impact of vitamin D supplementation remains uncertain. Rovner et al recently reported a randomized trial of high dose VitD 3 supplementation (7000 IU/day versus placebo) for 12 months in children and young adults between ages 5 and 25 years with perinatally-and behaviorally-acquired HIV infection.…”

The impact of vitamin D supplementation on musculoskeletal health outcomes in children, adolescents, and young adults living with HIV: A systematic review

“…Eckard et al . postulated a compensatory decrease in VDBP with EFV after cholecalciferol supplementation [ 88 ]. Their findings suggest that TDF and EFV may modify FGF23 response to vitamin D supplementation in adolescents living with HIV by altering vitamin D metabolism, at least in the short term [ 65 ].…”