Vitamin D3 supplementation scheme in HIV-infected patients based upon pharmacokinetic modelling of 25-hydroxycholecalciferol.
OBJECTIVE
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.
EA 3620 Université Paris Descartes, Sorbonne Paris Cité, France. frantz.foissac@cch.aphp.fr
Frantz
F
Foissac
Jean-Marc
JM
Tréluyer
Jean-Claude
JC
Souberbielle
Hafeda
H
Rostane
Saïk
S
Urien
Jean-Paul
JP
Viard
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000493:pharmacokinetics*; D002112:Calcifediol / Q000493:pharmacokinetics*; D002762:Cholecalciferol / Q000008:administration & dosage*; D019587:Dietary Supplements; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006679:HIV Seropositivity / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011863:Radioimmunoassay; D012189:Retrospective Studies; D012621:Seasons; D012880:Skin Pigmentation; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000378:metabolism*; D014815:Vitamins / Q000493:pharmacokinetics*; D055815:Young Adult
D044966:Anti-Retroviral Agents; D050071:Bone Density Conservation Agents; D014815:Vitamins; D002762:Cholecalciferol; D002112:Calcifediol