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

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).