Pharmacokinetics of Atazanavir Boosted With Cobicistat in Pregnant and Postpartum Women With HIV

J Acquir Immune Defic Syndr. 2022 Mar 1;89(3):303-309. doi: 10.1097/QAI.0000000000002856.

Abstract

Background: This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples.

Setting: A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children.

Methods: Intensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Atazanavir and cobicistat were measured in plasma by validated high-performance liquid chromatography-ultraviolet and liquid chromatography-tandem mass spectrometry assays, respectively. A 2-tailed Wilcoxon signed-rank test (α = 0.10) was used for paired within-participant comparisons.

Results: A total of 11 pregnant women enrolled in the study. Compared with paired postpartum data, atazanavir AUC0-24 was 26% lower in the second trimester [n = 5, P = 0.1875, geometric mean of ratio (GMR) = 0.739, 90% CI: 0.527 to 1.035] and 54% lower in the third trimester (n = 6, GMR = 0.459, P = 0.1563, 90% CI: 0.190 to 1.109), whereas cobicistat AUC0-24 was 35% lower in the second trimester (n = 5, P = 0.0625, GMR = 0.650, 90% CI: 0.493 to 0.858) and 52% lower in the third trimester (n = 7, P = 0.0156, GMR = 0.480, 90% CI: 0.299 to 0.772). The median (interquartile range) 24-hour atazanavir trough concentration was 0.21 μg/mL (0.16-0.28) in the second trimester, 0.21 μg/mL (0.11-0.56) in the third trimester, and 0.61 μg/mL (0.42-1.03) in postpartum. Placental transfer of atazanavir and cobicistat was limited.

Conclusions: Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission.

Trial registration: ClinicalTrials.gov NCT00042289.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents
  • Atazanavir Sulfate / pharmacokinetics*
  • Atazanavir Sulfate / therapeutic use
  • Child
  • Cobicistat
  • Female
  • HIV Infections* / drug therapy
  • HIV Protease Inhibitors*
  • Humans
  • Infectious Disease Transmission, Vertical
  • Placenta
  • Postpartum Period
  • Pregnancy
  • Pregnancy Complications, Infectious* / drug therapy
  • Prospective Studies

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Atazanavir Sulfate
  • Cobicistat

Associated data

  • ClinicalTrials.gov/NCT00042289