title: Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry.
abstract: 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 analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/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/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual 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 300,000 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.
authors.affiliation: School of Pharmaceutical Sciences, University of Lausanne and University of Geneva, Geneva, Switzerland.
authors.forename: Monia
authors.initials: M
authors.lastname: Guidi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Foletti
authors.forename: Paul
authors.initials: P
authors.lastname: McLaren
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Philip E
authors.initials: PE
authors.lastname: Tarr
authors.forename: Olivier
authors.initials: O
authors.lastname: Lamy
authors.forename: Alice
authors.initials: A
authors.lastname: Panchaud
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Chantal
authors.initials: C
authors.lastname: Csajka
authors.forename: Margalida
authors.initials: M
authors.lastname: Rotger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003198:Computer Simulation; D019587:Dietary Supplements; D004198:Disease Susceptibility; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy; D044465:White People; D055815:Young Adult
chemical_list: D014807:Vitamin D