Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry

Guidi, Monia; Foletti, Giuseppe; McLaren, Paul; Cavassini, Matthias; Rauch, Andri; Tarr, Philip E; Lamy, Olivier; Panchaud, Alice; Telenti, Amalio; Csajka, Chantal; Rotger, Margalida (2014). Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry. Antiviral therapy, 20(3), pp. 261-269. International Medical Press 10.3851/IMP2823

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Text VitD_POPPK_AVT_revised_v7_FINAL.pdf - Accepted Version Available under License Publisher holds Copyright. This is the author’s version of a work accepted for publication by International Medical Press. Changes resulting from the publishing process, including editing and formatting, might not be reflected in this document. A definitive version was published in Antiviral Therapy, (http://dx.doi.org/10.3851/IMP2823). ©2014 International Medical Press Download (311kB) | Preview

BACKGROUND

Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets.

METHODS

1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analyzed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40ng/ml during 12 months of follow up and several dosage regimens were evaluated by simulation.

RESULTS

A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/r and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the interindividual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300000 IU two times per year.

CONCLUSIONS

This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

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