Accepted for/Published in: JMIR Research Protocols
Date Submitted: Dec 19, 2025
Date Accepted: May 26, 2026
A Single Dose Longitudinal Pharmacokinetic Evaluation of Doravirine in Pregnant Women Living with HIV: Protocol for a Phase 1 Study
ABSTRACT
Background:
Women are largely under-represented in clinical trials of antiretroviral therapy, constituting approximately 20% of participants. Trials often exclude women of childbearing potential from participation to minimize fetal risk, and women enrolled in clinical trials having a positive pregnancy test may be discontinued from the study. This results in an average 7-year lag between the time of drug approval and when dosing information for pregnancy is available. However, there may be low-risk opportunities to obtain dosing information earlier for pregnant women who need treatment with newer medications. We demonstrate this with a clinical trial of doravirine, an FDA-approved non-nucleoside reverse transcriptase inhibitor, designed to assess the pharmacokinetics and dosing strategy for doravirine during pregnancy, while maintaining safety for participants.
Objective:
The primary objective of this study is to quantify single-dose total and protein-unbound pharmacokinetics of doravirine in blood plasma of women living with HIV during their second trimester, third trimester, and postpartum. The secondary objective is to evaluate the safety and tolerability of single doses of doravirine in pregnant participants living with HIV.
Methods:
The proposed study is a single-site Phase 1 evaluation of single doses of doravirine across the gestational period in gravid females living with HIV currently controlled on antiretroviral therapy. Single doses are given in the second and third trimester and postpartum. Pharmacokinetic sampling occurs over a 72-hour dosing interval, and total and protein-unbound drug concentrations are assessed across the three dosing phases.
Results:
The proposed study was approved by the local institutional review board on 09 March 2021. Participant recruitment began the same day, and the first participant was enrolled on 09 June 2022. In total seven participants were enrolled in the study and five were evaluable.
Conclusions:
The data collected with this novel single dose pharmacokinetic study design will provide important insights to clinically manage patients on doravirine during pregnancy and provides an effective model for obtaining early pharmacokinetic and dosing information for new drugs that will be used in pregnant women. Clinical Trial: NCT04900974
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