Vitamin D₃ supplementation scheme in HIV‐infected patients based upon pharmacokinetic modelling of 25‐hydroxycholecalciferol

Aims

Vitamin D deficiency is prevalent in HIV‐infected patients and has been associated with osteopenia and HIV disease progression. Our aims were to investigate the pharmacokinetics of 25‐hydroxycholecalciferol [25(OH)D], the effect of antiretroviral treatment (ARV) and others factors that may influence the pharmacokinetics, and to determine a vitamin D₃ dosing scheme to reach the 30 ng ml⁻¹ threshold (defined as 25(OH)D sufficiency).

Methods

This monocentric retrospective study included 422 HIV‐infected patients aged 16 to 85 years. A total of 723 25(OH)D concentrations were available for pharmacokinetic evaluation and a population pharmacokinetic model was developed with MONOLIX 3.2.

Results

Median 25(OH)D at baseline was 16 ng ml⁻¹ (interquartile range 11–23 ng ml⁻¹) for the total population, 17% of patient had concentrations below 10 ng ml⁻¹, 68% between 10 and 30 ng ml⁻¹ and 15% above 30 ng ml⁻¹. 25(OH)D pharmacokinetics were best described by a one compartment model with an additional endogenous production. The effects of season and skin phototype were significant on production rate. The endogenous production was 20% lower in non‐white skin phototype patients and was decreased by 16% during autumn, winter and spring. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs (ARV). To obtain concentrations between 30 and 80 ng ml⁻¹, the dosing recommendation was 100 000 IU every month.

Conclusions

Season and skin phototype had an influence on the endogenous production of 25(OH)D. However no effect of ARV was found. A dosing scheme to reach sufficient 25(OH)D concentrations is proposed.

DOI: 10.1111/bcp.12006

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