Pharmacokinetic Changes during Pregnancy According to Genetic Variants: a Prospective Study in HIV-Infected Patients Receiving Atazanavir-Ritonavir

Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00309-18. doi: 10.1128/AAC.00309-18. Print 2018 Jul.

Abstract

Atazanavir-ritonavir concentrations change over time during pregnancy in HIV-positive patients; the impact of genetic variants is unknown. Twenty patients were enrolled in this study; plasma and intracellular concentrations of antiretrovirals were measured, in addition to single-nucleotide polymorphisms in transport-related genes. Linear logistic regression showed that genetic variants in organic-anion-transporter-1B1- and pregnane-X-receptor-encoding genes affected third-trimester atazanavir exposure. In this prospective study, genetic variants partially explained the observed interpatient variability in third-trimester exposure to antiretrovirals.

Keywords: HIV; antiretroviral agents; antiviral pharmacology.

MeSH terms

  • Adult
  • Atazanavir Sulfate / blood
  • Atazanavir Sulfate / pharmacokinetics*
  • Atazanavir Sulfate / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Trimester, Third
  • Pregnane X Receptor / genetics*
  • Prospective Studies
  • Ritonavir / blood
  • Ritonavir / pharmacokinetics*
  • Ritonavir / therapeutic use*

Substances

  • HIV Protease Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • NR1I2 protein, human
  • Pregnane X Receptor
  • SLCO1B1 protein, human
  • Atazanavir Sulfate
  • Ritonavir