Use of Tenofovir disoproxil fumarate (Hepatitis-B, AIDS) requires more vitamin D – Sept 2018

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

Antivir Ther. 2018 Sep 27. doi: 10.3851/IMP3269
Havens PL1, Long D2, Schuster GU3, Gordon CM4, Price G5, Wilson CM6, Kapogiannis BG7, Mulligan K8, Stephensen CB9; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 117 and 109 study teams.

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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Vitamin D as Modulator of Drug Concentrations:
A Study on Two Italian Cohorts of People Living with HIV Administered with Efavirenz

Nutrients. 2021 Oct 12;13(10):3571. doi: 10.3390/nu13103571.
Jessica Cusato 1, Massimo Tempestilli 2, Andrea Calcagno 3, Alessandra Vergori 2, Pierluca Piselli 2, Miriam Antonucci 1, Valeria Avataneo 1, Alice Palermiti 1, Stefania Notari 2, Andrea Antinori 2, Giovanni Di Perri 3, Chiara Agrati 2, Antonio D'Avolio 1

To date, vitamin D seems to have a significant role in affecting the prevention and immunomodulation in COVID-19 disease. Nevertheless, it is important to highlight that this pro-hormone has other several activities, such as affecting drug concentrations, since it regulates the expression of cytochrome P450 (CYP) genes. Efavirenz (EFV) pharmacokinetics is influenced by CYPs, but no data are available in the literature concerning the association among vitamin D levels, seasonality (which affects vitamin D concentrations) and EFV plasma levels. For this reason, the aim of this study was to evaluate the effect of 25-hydroxy vitamin D (25(OH)D3) levels on EFV plasma concentrations in different seasons. We quantified 25(OH)D3 by using chemiluminescence immunoassay, whereas EFV plasma concentrations were quantified with the HPLC-PDA method. A total of 316 patients were enrolled in Turin and Rome. Overall, 25(OH)D3levels resulted in being inversely correlated with EFV concentrations. Some patients with EFV levels higher than 4000 ng/mL showed a deficient 25(OH)D3 concentration in Turin and Rome cohorts and together. EFV concentrations were different in patients without vitamin D supplementation, whereas, for vitamin D-administered individuals, no difference in EFV exposure was present. Concerning seasonality, EFV concentrations were associated with 25(OH)D3 deficiency only in winter and in spring, whereas a significant influence was highlighted for 25(OH)D3 stratification for deficient, insufficient and sufficient values in winter, spring and summer. A strong and inverse association between 25(OH)D3and EFV plasma concentrations was suggested. These data suggest that vitamin D is able to affect drug exposure in different seasons; thus, the achievement of the clinical outcome could be improved by also considering this pro-hormone.
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