Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youths treated with tenofovir disoproxil fumarate.

TitleVitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youths treated with tenofovir disoproxil fumarate.
Publication TypePublication
Year of Publication2014
AuthorsHavens PL, Hazra R, Stephensen CB, Kiser JJ, Flynn PM, Wilson CM, Rutledge B, Bethel J, Pan CG, Woodhouse LR, Van Loan MD, Liu N, Lujan-Zilbermann J, Baker A, Kapogiannis BG, Gordon CM, Mulligan K
Corporate AuthorsAdolescent Medicine Trials Network for HIV/AIDS Interventions(ATN) 063 Study Team
JournalAntivir Ther
Volume19
Issue6
Pagination613-8
Date Published2014
ISSN2040-2058
KeywordsAdenine, Adolescent, Adult, Anti-HIV Agents, Cholecalciferol, Dietary Supplements, Female, Fibroblast Growth Factors, HIV Infections, Humans, Male, Organophosphonates, Reverse Transcriptase Inhibitors, Tenofovir, Treatment Outcome, Young Adult
Abstract

<p><b>BACKGROUND: </b>Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor 23 (FGF23) causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D-binding protein (VDBP) binds to 1,25-OH(2)D, decreasing its biological activity, and is elevated in individuals with higher plasma tenofovir concentrations. We compared FGF23 and VDBP before and after vitamin D3 (VITD) supplementation in youths treated with combination antiretroviral therapy (cART) containing or not containing TDF.</p><p><b>METHODS: </b>A randomized controlled trial in HIV-positive youths aged 18-25 years enrolled participants based on cART treatment with TDF (TDF; n=118) or without TDF (no-TDF; n=85), and randomized within those groups to VITD (50,000 IU every 4 weeks) or placebo (PL). We measured FGF23 and VDBP and calculated free 1,25-OH(2)D at baseline and week 12, and compared changes by TDF treatment and VITD randomized group.</p><p><b>RESULTS: </b>At baseline, serum FGF23 concentration showed a quadratic relationship with 1,25-OH(2)D most pronounced in the TDF group. At week 12, total and free 1,25-OH(2)D increased in the VITD but not PL groups, independent of TDF use. FGF23 increased in the TDF group receiving VITD, but there was no FGF23 change in the no-TDF group receiving VITD or the PL groups. The adjusted mean change in FGF23 from baseline to week 12 was 7.7 pg/ml in the TDF/VITD group, compared with -1.7 (no-TDF/VITD, P=0.010), -1.3 (TDF/PL, P=0.006) and 1.1 (no-TDF/PL, P=0.035).</p><p><b>CONCLUSIONS: </b>These results suggest that TDF-containing cART may alter the FGF23 response to vitamin D supplementation in HIV-infected youths. Clinical trials number: NCT00490412.</p>

DOI10.3851/IMP2755
Alternate JournalAntivir. Ther. (Lond.)
PubMed ID24535626
PubMed Central IDPMC4135028
Grant ListUL1-RR02517 / RR / NCRR NIH HHS / United States
U01 HD 040533 / HD / NICHD NIH HHS / United States
UL1-RR025014 / RR / NCRR NIH HHS / United States
U01 HD040533 / HD / NICHD NIH HHS / United States
U01 HD 040474 / HD / NICHD NIH HHS / United States
U01 HD040474 / HD / NICHD NIH HHS / United States
M01-RR10710 / RR / NCRR NIH HHS / United States
M01-RR00188 / RR / NCRR NIH HHS / United States
U01 HD040497 / HD / NICHD NIH HHS / United States
M01 RR000188 / RR / NCRR NIH HHS / United States
UL1 RR024131 / RR / NCRR NIH HHS / United States
M01 RR010710 / RR / NCRR NIH HHS / United States
RUL1-RR-024134 / / Cancer Research UK / United Kingdom
UL1 RR025014 / RR / NCRR NIH HHS / United States
UL1 TR002319 / TR / NCATS NIH HHS / United States
M01RR020359 / RR / NCRR NIH HHS / United States
UL1 RR024134 / RR / NCRR NIH HHS / United States
M01 RR020359 / RR / NCRR NIH HHS / United States