Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy

J Clin Pharmacol. 2020 Dec;60(12):1537-1550. doi: 10.1002/jcph.1714. Epub 2020 Aug 14.

Abstract

Pharmacokinetic boosting of antiretroviral (ARV) therapies with either ritonavir or cobicistat is used to achieve target drug exposure, lower pill burden, and provide simplified dosing schedules. Several ARVs require boosting, including the integrase inhibitor elvitegravir as well as protease inhibitors such as darunavir, atazanavir, and lopinavir. The use of boosted regimens in pregnant women living with HIV has been studied for a variety of ARVs; however, a recent recommendation by the US Food and Drug Administration advised against cobicistat-boosted regimens in pregnancy due to substantially lower drug exposures observed in clinical pharmacokinetic studies. The objectives of this article are to review pharmacokinetic enhancement of ARVs with ritonavir and cobicistat during pregnancy and postpartum, describe clinical implications, and provide recommendations for future research.

Keywords: HIV; cobicistat; drug metabolism; pharmacokinetics; pregnancy; ritonavir.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Cobicistat / pharmacology*
  • Cobicistat / therapeutic use
  • Cytochrome P-450 CYP3A Inhibitors / pharmacology*
  • Cytochrome P-450 CYP3A Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Postpartum Period
  • Pregnancy
  • Ritonavir / pharmacology*
  • Ritonavir / therapeutic use

Substances

  • Anti-HIV Agents
  • Cytochrome P-450 CYP3A Inhibitors
  • Cobicistat
  • Ritonavir