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United States Department of Agriculture

Agricultural Research Service

Research Project: Assessing the Impact of Diet on Inflammation in Healthy and Obese Adults in a Cross-Sectional Phenotyping Study and a Longitudinal Intervention Trial

Location: Immunity and Disease Prevention Research

Title: Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

Author
item Havens, Peter
item Stephensen, Charles
item Van Loan, Marta
item Schuster, Gertrud
item Woodhouse, Leslie
item Flynn, Patricia
item Gordon, Catherine
item Pan, Cynthia
item Rutledge, Brandy
item Harris, Bob
item Price, Georgine
item Meyer, William
item Hazra, Rohan
item Kapogiannis, Bill
item Mulligan, Kathleen

Submitted to: Clinical Infectious Diseases
Publication Type: Trade Journal
Publication Acceptance Date: 8/9/2017
Publication Date: 8/21/2017
Citation: Havens, P.L., Stephensen, C.B., Van Loan, M.D., Schuster, G.U., Woodhouse, L.R., Flynn, P.M., Gordon, C.M., Pan, C.G., Rutledge, B., Harris, B., Price, G., Meyer, W.M., Hazra, R., Kapogiannis, B.G., Mulligan, K. 2017. Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial. Clinical Infectious Diseases. doi/10.1093/cid/cix753.

Interpretive Summary: People with HIV infection take drugs to control their infection and maintain health. Tenofovir disoproxil fumarate (TDF) is one of these drugs and it has the significant side-effect of decreasing bone mineral density, which can result in bone fractures. This is a major side-effect and we conducted the study described in this manuscript to determine if supplementation with extra vitamin D3, which is needed to maintain good bone health, would increase bone mineral density in adolescents and young adults receiving TDF. This was a randomized double-blind placebo-controlled trial of directly observed vitamin D3 supplementation at a dose of 50,000 IU as compared to a placebo pill. Each treatment was given every 4 weeks for 48 weeks in youth ages 16-24 years with HIV infection who were taking TDF-containing combination antiretroviral therapy. Participants (N=214) received a daily multivitamin containing vitamin D3 (400 IU) and calcium (162 mg) plus their monthly randomized vitamin D3 (“high-dose;” N=109) or placebo (“low-dose;” N=105). The principal outcome of interest for this study was change from baseline to week 48 in lumbar spine (L1-L4) bone mineral density. Participants had an average age of 22 years, 84% were male, and 74% were African American. The prevalence of vitamin D deficiency/insufficiency (serum 25-hydroxy vitamin D [25-OHD] <20 ng/mL) at baseline was 62%. Serum 25-OHD increased significantly in the group receiving the high-dose vitamin D3, relative to the control group. From baseline to week 48, lumbar spine bone mineral density increased by 1.15% in the high-dose group but only by 0.09% in the low-dose group, In conclusion, the high-dose but not low-dose vitamin D3 treatment improved lumbar spine bone mineral density, suggesting that vitamin D3 treatment may be a beneficial adjunct treatment to TDF therapy in those living with HIV infection.

Technical Abstract: Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 weeks for 48 weeks in youth ages 16-24 years with HIV, viral load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (cART) for >180 days. Participants (N=214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg plus monthly randomized VITD3 (“high-dose;” N=109) or placebo (“low-dose;” N=105). Outcome was change from baseline to week 48 in lumbar spine (L1-L4) BMD (LSBMD). Data are presented as median(interquartile range). Results: Participants were age 22.0(2.0) years, 84% male, and 74% black/African American. Prevalence of VITD deficiency/insufficiency (25-hydroxy vitamin D [25-OHD] <20 ng/mL) at baseline was 62%. Multivitamin adherence was 49(42)% and VITD/placebo adherence 100 (0)%. VITD intake was 2020(254) and 284(215) IU/day. Serum 25-OHD concentration was 36.9(11.9) and 20.6(11.5) ng/mL at 48 weeks in high- and low-dose groups, respectively (P<0.001). From baseline to week 48, LSBMD increased by 1.15(3.50)% in the high-dose group (N=99; P<0.001) and 0.09(4.10)% in the low-dose group (N=89; P=0.252), without between-group difference (P=0.117). In the high-dose group these changes occurred with baseline 25-OHD < 20 ng/mL (1.17[3.72]%; P=0.004) and baseline 25-OHD >20 ng/mL (0.93[2.41]%; P=0.033). No changes occurred in hip or whole-body BMD. Conclusions: For youth with HIV treated with TDF-containing cART, high-dose, but not low-dose, VITD3 supplementation increased LSBMD through 48 weeks, independent of baseline VITD status.

Last Modified: 09/24/2017
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