Clinically Significant Lower Elvitegravir Exposure During the Third Trimester of Pregnant Patients Living With Human Immunodeficiency Virus: Data From the Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) Network

Vera Bukkems, Coca Necsoi, Carmen Hidalgo Tenorio, Coral Garcia, Jürgen Rockstroh, Caroline Schwarze-Zander, John S Lambert, David Burger, Deborah Konopnicki, Angela Colbers, Vera Bukkems, Coca Necsoi, Carmen Hidalgo Tenorio, Coral Garcia, Jürgen Rockstroh, Caroline Schwarze-Zander, John S Lambert, David Burger, Deborah Konopnicki, Angela Colbers

Abstract

This phase 4 study investigated the influence of pregnancy on the pharmacokinetics of elvitegravir/cobicistat in 14 women with human immunodeficiency virus type 1. The results support the recommendation against elvitegravir/cobicistat use during pregnancy, as the elvitegravir concentration at the end of the dosing interval (Ctrough) was reduced by 77%, with 85% of pregnant women having a Ctrough below the effective concentration (EC90). Clinical Trials Registration. NCT00825929.

Keywords: HIV; cobicistat; elvitegravir; pharmacokinetics; pregnancy.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

References

    1. Momper JD, Best BM, Wang J, et al. . IMPAACT P1026s Protocol Team Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV. AIDS 2018; 32:2507–16.
    1. US Food and Drug Administration. FDA revises certain antiretroviral drug labeling to not recommend cobicistat during pregnancy. In: FDA News, Issue 33, 2018. Available at: . Accessed 8 January 2020.
    1. Blonk MI, Colbers AP, Hidalgo-Tenorio C, et al. . Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women PANNA Network; PANNA Network Raltegravir in HIV-1-infected pregnant women: pharmacokinetics, safety, and efficacy. Clin Infect Dis 2015; 61:809–16.
    1. DiFrancesco R, Tooley K, Rosenkranz SL, et al. . Clinical pharmacology quality assurance for HIV and related infectious diseases research. Clin Pharmacol Ther 2013; 93:479–82.
    1. Ramanathan S, Mathias AA, German P, Kearney BP. Clinical pharmacokinetic and pharmacodynamic profile of the HIV integrase inhibitor elvitegravir. Clin Pharmacokinet 2011; 50:229–44.
    1. European Medicines Agency. Genvoya; summary of product characteristics Available at: . Accessed 8 January 2020.
    1. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013; 13:59.
    1. Marzolini C, Decosterd L, Winterfeld U, et al. . Free and total plasma concentrations of elvitegravir/cobicistat during pregnancy and postpartum: a case report. Br J Clin Pharmacol 2017; 83:2835–8.
    1. Aweeka FT, Hu C, Huang L, et al. . International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1026s Protocol Team Alteration in cytochrome P450 3A4 activity as measured by a urine cortisol assay in HIV-1-infected pregnant women and relationship to antiretroviral pharmacokinetics. HIV Med 2015; 16:176–83.
    1. US Food and Drug Administration. Tybost: clinical pharmacology and biopharmaceutical review(s). Available at: . Accessed 8 January 2020.
    1. Anderson GD. Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach. Clin Pharmacokinet 2005; 44:989–1008.
    1. Schalkwijk S, Greupink R, Burger D. Free dug concentrations in pregnancy: bound to measure unbound? Br J Clin Pharmacol 2017; 83:2595–8.
    1. Badell ML, Sheth AN, Momplaisir F, et al. . A multicenter analysis of elvitegravir use during pregnancy on HIV viral suppression and perinatal outcomes. Open Forum Infect Dis 2019; 6: ofz129.

Source: PubMed

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