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Clin Infect Dis. 2018 Jan 6;66(2):220-228. doi: 10.1093/cid/cix753.

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial.

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Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee.
Agricultural Research Service, Western Human Nutrition Research Center, US Department of Agriculture, Davis.
Department of Nutrition, University of California, Davis.
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee.
Department of Pediatrics, University of Cincinnati College of Medicine/Cincinnati Children's Hospital Medical Center, Ohio.
Westat, Rockville, Maryland.
Tulane University of Health Sciences Center, New Orleans, Louisiana.
Quest Diagnostics, Baltimore, Maryland.
Department of Epidemiology, University of Alabama at Birmingham.
Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Department of Medicine, Division of Endocrinology, Zuckerberg San Francisco General Hospital, University of California, San Francisco.



Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF.


This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3).


Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033).


For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status.

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HIV infection; bone mineral density; parathyroid hormone; tenofovir disoproxil fumarate; vitamin D supplementation

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