Antiretroviral unbound concentration during pregnancy: piece of interest in the puzzle?

J Antimicrob Chemother. 2017 Sep 1;72(9):2407-2409. doi: 10.1093/jac/dkx176.


Atazanavir and darunavir total concentrations (drug bound to plasma proteins plus unbound drug) progressively decrease during pregnancy. This pharmacokinetic variation leads physicians to recommend increasing doses. Conversely, the unbound concentration (Cu), i.e. the pharmacologically active form of the drug, remains unchanged. The explanation of this desynchronization lies in the fact that the clearance of the unbound form, corresponding to the intrinsic metabolic capacity of the hepatocytes, is the only factor driving Cu, and is constant during pregnancy. The attention of HIV physicians should be attracted to this aspect of pharmacokinetics, which is often incompletely understood and could lead to inadequate dose adjustment, which could then cause overexposure of the foetus for many months, with unknown consequences.

MeSH terms

  • Atazanavir Sulfate / adverse effects
  • Atazanavir Sulfate / chemistry
  • Atazanavir Sulfate / pharmacokinetics*
  • Atazanavir Sulfate / therapeutic use
  • Blood Proteins / chemistry
  • Blood Proteins / metabolism
  • Darunavir / adverse effects
  • Darunavir / chemistry
  • Darunavir / pharmacokinetics*
  • Darunavir / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacokinetics*
  • HIV Protease Inhibitors / therapeutic use
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Pregnancy
  • Protein Binding


  • Blood Proteins
  • HIV Protease Inhibitors
  • Atazanavir Sulfate
  • Darunavir