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. 2021 Oct 12;13(10):3571.
doi: 10.3390/nu13103571.

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

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
Affiliations

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

Jessica Cusato et al. Nutrients. .

Abstract

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.

Keywords: drug metabolism; plasma concentrations; seasonality; vitamin D.

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Conflict of interest statement

A.C. and G.D.P. reports grants from VIIV and GILEAD, as well as personal fees from VIIV, GILEAD, JANSSEN-CILAG, INSMED and MSD, outside the submitted work. A.V. received institutional grant from Gilead Sciences, personal fees and travel grant from Janssen, personal fee from MSD. A.A. has served as a paid consultant to Gilead Sciences, Janssen-Cilag, Merck and ViiV Healthcare and received research institutional grants from Gilead Sciences, Janssen-Cilag and ViiV Healthcare. The other authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Efavirenz exposure according to 25-hydroxyvitamin D (25(OH)D3) level stratification (deficiency, insufficiency and sufficiency). Circles and stars indicate “out” values (small circle) and “far out” values (star).
See this image and copyright information in PMC

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