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

Peter L Havens, Dustin Long, Gertrud U Schuster, Catherine M Gordon, Georgine Price, Craig M Wilson, Bill G Kapogiannis, Kathleen Mulligan, Charles B Stephensen, the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 117 and 109 study teams

Corresponding author name: Peter L Havens
Corresponding author e-mail: phavens@mcw.edu

doi: 10.3851/IMP3269

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 3 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 17-24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r= -.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.

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