title: Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youths treated with tenofovir disoproxil fumarate.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  These results suggest that TDF-containing cART may alter the FGF23 response to vitamin D supplementation in HIV-infected youths. Clinical trials number: NCT00490412.
authors.affiliation: Children's Research Institute, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, WI, USA. phavens@mcw.edu.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Havens
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Charles B
authors.initials: CB
authors.lastname: Stephensen
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Kiser
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Flynn
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Brandy
authors.initials: B
authors.lastname: Rutledge
authors.forename: James
authors.initials: J
authors.lastname: Bethel
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Pan
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Woodhouse
authors.forename: Marta D
authors.initials: MD
authors.lastname: Van Loan
authors.forename: Nancy
authors.initials: N
authors.lastname: Liu
authors.forename: Jorge
authors.initials: J
authors.lastname: Lujan-Zilbermann
authors.forename: Alyne
authors.initials: A
authors.lastname: Baker
authors.forename: Bill G
authors.initials: BG
authors.lastname: Kapogiannis
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Gordon
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019587:Dietary Supplements; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C000717427:FGF23 protein, human; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D002762:Cholecalciferol; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000068698:Tenofovir; D000225:Adenine