Tenofovir Alafenamide Plasma Concentrations Are Reduced in Pregnant Women Living With Human Immunodeficiency Virus (HIV): Data From the PANNA Network.

Background: Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is included in the majority of the recommended first-line antiretroviral regimens for patients living with human immunodeficiency virus (HIV), but there are limited data on TAF use in pregnant women. We aimed to examine the plasma pharmacokinetics of TAF and TFV in pregnant women from Europe.
Methods: Pregnant women living with HIV were included from treatment centers across Europe, and intensive pharmacokinetic sampling in the third trimester and postpartum was performed. Pharmacokinetic parameters of TAF and TFV were determined with noncompartmental analysis. The proportion of women with a TAF area under the curve (AUClast) below the target of 53.1 ng∗h/mL was determined. Clinical efficacy and safety outcome parameters were reported.
Results: In total, 20 pregnant women living with HIV were included. At the third trimester, geometric mean TAF AUClast and Cmax were decreased by 46% and 52%, respectively, compared with postpartum. TFV AUC0-24h, Cmax, and Ctrough decreased by 33%, 30%, and 34%, respectively. The proportion of women with a TAF AUClast < 53.1 ng∗h/mL was 6% at third trimester and 0% postpartum. One out of 20 women had a viral load > 50 copies/mL at third trimester and no mother-to-child transmission occurred.
Conclusions: TAF plasma concentrations were reduced by about half in women living with HIV during third trimester of pregnancy but remained above the predefined efficacy target in the majority of the pregnant women. TFV concentrations were reduced by approximately 30% during third trimester. Despite the observed exposure decrease, high virologic efficacy was observed in this study.
Competing Interests: Potential conflicts of interest. O. R. has received support from Gilead Sciences to attend the EACS conference. D. B. has received honoraria and/or study grants from Janssen Pharmaceutica, Merck Sharp & Dohme Corp, Gilead Sciences and ViiV Healthcare. D. K. has received payment/honoria from Janssen Pharmaceutica for a presentation on a HIV symposium; participates on an advisory board on HPV vaccines of Merck Sharp & Dohme Corp; received support from Gilead Sciences, Viiv Healthcare and Pfizer to attend the ID-week and the ECCMID. A. C. has received honoraria from Merck Sharp & Dohme Corp 2021, fee is paid to the institution; is an unpaid co-chair of the pediatric antiretroviral working group (PAWG). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)