Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone

Antivir Ther. 2018;23(7):623-628. doi: 10.3851/IMP3269. Epub 2018 Sep 27.

Abstract

Background: Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)2D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities.

Methods: Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)2D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses.

Results: Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)2D had the positive correlation similar to that found in vitamin D deficiency.

Conclusions: TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health.

Clinical trials registration: NCT01751646 (ATN 109) and NCT01769469 (ATN 117).

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • African Americans
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects*
  • Antiretroviral Therapy, Highly Active
  • Bone Density / drug effects
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Cohort Studies
  • Emtricitabine / therapeutic use*
  • European Continental Ancestry Group
  • Female
  • HIV / drug effects
  • HIV / growth & development
  • HIV / pathogenicity
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / ethnology
  • HIV Infections / virology
  • Humans
  • Male
  • Parathyroid Hormone / blood*
  • Pre-Exposure Prophylaxis / methods
  • Tenofovir / administration & dosage
  • Tenofovir / adverse effects*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / ethnology
  • Vitamin D Deficiency / prevention & control
  • Vitamin D Deficiency / virology
  • Young Adult

Substances

  • Anti-HIV Agents
  • Parathyroid Hormone
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • Tenofovir
  • 25-hydroxyvitamin D
  • Emtricitabine

Associated data

  • ClinicalTrials.gov/NCT01751646
  • ClinicalTrials.gov/NCT01769469