Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV

AIDS. 2018 Nov 13;32(17):2507-2516. doi: 10.1097/QAD.0000000000001992.

Abstract

Objective: To evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.

Design: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the United States.

Methods: Intensive steady-state 24-h pharmacokinetic profiles after 150 mg of elvitegravir and 150 mg of cobicistat given orally in fixed dose combination once-daily were performed during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Elvitegravir and cobicistat were measured in plasma by a validated liquid chromatography with tandem mass spectrometry assay with a lower quantitation limit of 10 ng/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons.

Results: Thirty pregnant women taking elvitegravir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, elvitegravir AUC0-24 was 24% lower in the second trimester [n = 14, P = 0.058, geometric mean ratios (GMR) = 0.76, 90% confidence interval (CI) 0.57-1.0] and 44% lower in the third trimester (n = 24, P = 0.0001, GMR = 0.56, 90% CI 0.42-0.73), while cobicistat AUC0-24 was 44% lower in the second trimester (n = 14, P = 0.0085, GMR = 0.56, 90% CI 0.37-0.85) and 59% lower in the third trimester (n = 24, P < 0.0001, GMR = 0.41, 90% CI 0.30-0.57). Median cord blood elvitegravir concentration was 540.6 ng/ml and the median ratio of cord blood to maternal plasma elvitegravir concentrations was 0.91.

Conclusion: Standard elvitegravir and cobicistat dosing during pregnancy results in significantly lower exposure which may increase the risk of virologic failure and mother-to-child transmission. Additional studies are needed to optimize elvitegravir and cobicistat dosing regimens in pregnant women.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics*
  • Chromatography, Liquid
  • Cobicistat / administration & dosage
  • Cobicistat / pharmacokinetics*
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Infant, Newborn
  • Middle Aged
  • Plasma / chemistry
  • Postpartum Period*
  • Pregnancy Complications, Infectious / drug therapy*
  • Pregnancy*
  • Prospective Studies
  • Quinolones / administration & dosage
  • Quinolones / pharmacokinetics*
  • Tandem Mass Spectrometry
  • United States
  • Young Adult

Substances

  • Anti-HIV Agents
  • JTK 303
  • Quinolones
  • Cobicistat