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

Abstract

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

Methods: 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).

Results: 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).

Conclusions: 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.

Clinical trials registration: NCT01751646.

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

Figure 1.

Participant flow diagram. ¹See Methods for eligibility criteria. Abbreviations: DOT, directly observed therapy; DXA, dual-energy X-ray absorptiometry.

Figure 2.

Serum vitamin D (25-OHD) concentration and change in lumbar spine (L1–L4) bone mineral density (BMD) by study week and vitamin D randomized dose group. Data are median and bars are Q1, Q3. P values shown in the figures are for the change from baseline to each study week. A, For both the vitamin D3 and placebo group, 25-OHD values at weeks 12, 24, and 48 were significantly higher than baseline. *25-OH-D change from baseline differed between dose groups (P < .001). ^†25-OHD at weeks 12, 24, and 48 differed between dose groups (P < .001). Vitamin D3, n = 100; placebo, n = 91. B, At week 48, the change from baseline was significant in the vitamin D3 group but not in the placebo group. There was no significant difference in the change from baseline to week 48 between the vitamin D3 and placebo groups (P = .117). C, Vitamin D3, n = 99; placebo, n = 89; 25-OHD <20 ng/mL, n = 59; 25-OHD >20 ng/mL, n = 40.

Figure 3.

Vitamin D status (serum 25-OHD category) by study week and vitamin D randomized dose group. Classification of vitamin D status based on Institute of Medicine categories [21]. At baseline, both vitamin D3 and placebo groups had about 60% of participants with vitamin D deficiency/insufficiency (25-OHD <20 ng/mL).