{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:25:54Z","timestamp":1791930354111,"version":"4.3.4"},"reference-count":16,"publisher":"JMIR Publications Inc.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMIR Res Protoc"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Women are largely underrepresented in clinical trials of antiretroviral therapy, constituting approximately 20% of participants. Trials often exclude pregnant women from participation to minimize fetal risk, and women enrolled in clinical trials who have 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, a Food and Drug Administration (FDA)\u2013approved nonnucleoside reverse transcriptase inhibitor, designed to assess the pharmacokinetics and dosing strategy for doravirine during pregnancy while maintaining safety for participants.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n The primary objective of this study is to quantify single-dose total and protein-unbound pharmacokinetics of doravirine in blood plasma from women living with HIV during their second trimester, third trimester, and postpartum periods. The secondary objective is to evaluate the safety and tolerability of single doses of doravirine in pregnant participants living with HIV.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The proposed study is a single-site phase 1 evaluation of single doses of doravirine across the gestational period in pregnant female participants (n=10) living with HIV currently controlled with antiretroviral therapy. Single doses were administered in the second and third trimesters and postpartum. Pharmacokinetic sampling occurred over a 72-hour dosing interval, and total and protein-unbound drug concentrations were assessed across the 3 dosing phases using LC-MS\/MS methods validated according to FDA criteria. Pharmacokinetic parameters of peak drug concentration, concentration at 12 hours into the dosing interval, concentration at the end of the dosing interval, time to reach maximum concentration, and area under the curve were estimated using noncompartmental linear up-log down methods (version 8.6; Phoenix WinNonlin). Comparisons across the 3 sampling visits were made using the Friedman test and post hoc Wilcoxon signed-rank tests with Bonferroni adjustment (version 13.0; SigmaPlot).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The proposed study was funded in 2020 and approved by the University of North Carolina-Chapel Hill institutional review board on March 9, 2021. Participant recruitment began the same day, and the first participant was enrolled on June 9, 2022. The last participant was enrolled on October 3, 2024, and all participants were off the study on April 8, 2025. In total, 7 participants were enrolled in the study, and 5 were evaluable.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The data collected with this novel single-dose pharmacokinetic study design will provide important insights into the clinical management of patients on doravirine during pregnancy and provide an effective model for obtaining early pharmacokinetic and dosing information for new drugs that can be used in pregnant women.<\/jats:p>\n <\/jats:sec>","DOI":"10.2196\/89990","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:11:14Z","timestamp":1783692674000},"page":"e89990-e89990","source":"Crossref","is-referenced-by-count":1,"title":["Single-Dose Longitudinal Pharmacokinetic Evaluation of Doravirine in Pregnant Women Living With HIV: Protocol for a Phase 1 Study"],"prefix":"10.2196","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0150-0500","authenticated-orcid":false,"given":"Amanda","family":"Poliseno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4444-7969","authenticated-orcid":false,"given":"Lisa","family":"Rahangdale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3620-3059","authenticated-orcid":false,"given":"Cynthia","family":"Gay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0400-0177","authenticated-orcid":false,"given":"Emma","family":"Trawick Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9171-8493","authenticated-orcid":false,"given":"Angela","family":"Kashuba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1010","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"R1","unstructured":"HIV - prevention of mother-to-child transmission. World Health Organization. URL: https:\/\/www.who.int\/data\/gho\/data\/themes\/topics\/indicator-groups\/indicator-group-details\/GHO\/prevention-of-mother-to-child-transmission [Accessed 17-06-2026]"},{"issue":"12","key":"R2","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25846","article-title":"Ending the evidence gap for pregnancy, HIV and co-infections: ethics guidance from the PHASES project","volume":"24","author":"Lyerly","journal-title":"J Int AIDS Soc"},{"issue":"9","key":"R3","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25372","article-title":"Inclusion of pregnant women in antiretroviral drug research: what is needed to move forwards?","volume":"22","author":"Fairlie","journal-title":"J Int AIDS Soc"},{"issue":"7","key":"R4","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics17070913","article-title":"Pharmacokinetic adaptations in pregnancy: implications for optimizing antiretroviral therapy in HIV-positive women","volume":"17","author":"Brice\u00f1o-Pati\u00f1o","journal-title":"Pharmaceutics"},{"issue":"7","key":"R5","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1093\/cid\/ciz121","article-title":"Importance of prospective studies in pregnant and breastfeeding women living with human immunodeficiency virus","volume":"69","author":"Colbers","journal-title":"Clin Infect Dis"},{"key":"R6","unstructured":"Task force on research specific to pregnant women and lactating women: report to Secretary, Health and Human Services Congress. National Institute of Child Health and Human Development; 2018. URL: https:\/\/www.nichd.nih.gov\/sites\/default\/files\/2018-09\/PRGLAC_Report.pdf [Accessed 17-06-2026]"},{"issue":"14","key":"R7","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1056\/NEJMp1815325","article-title":"Pharmacologic research in pregnant women - time to get it right","volume":"380","author":"Eke","journal-title":"N Engl J Med"},{"key":"R8","unstructured":"DELSTRIGO\u00ae (doravirine, lamivudine, and tenofovir disoproxil fumarate) tablets, for oral use. Merck & Co. 2025. URL: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/210807s016lbl.pdf [Accessed 17-06-2026]"},{"key":"R9","unstructured":"Antiretroviral pregnancy registry interim report for 1 January 1989 through 31 July 2025. Registry Coordinating Center; 2025. URL: https:\/\/www.apregistry.com\/forms\/interim_report.pdf [Accessed 17-06-2026]"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.2196\/41188","article-title":"Establishing novel antiretroviral imaging for hair to elucidate nonadherence: protocol for a single-arm cross-sectional study","volume":"12","author":"Poliseno","journal-title":"JMIR Res Protoc"},{"key":"R11","unstructured":"ICH harmonised guideline: guideline for good clinical practice E6(R3). International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; 2025. URL: https:\/\/database.ich.org\/sites\/default\/files\/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf [Accessed 17-06-2026]"},{"key":"R12","unstructured":"Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events. National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services; 2017. URL: https:\/\/rsc.niaid.nih.gov\/sites\/default\/files\/daidsgradingcorrectedv21.pdf [Accessed 17-06-2026]"},{"issue":"4","key":"R13","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3851\/IMP2920","article-title":"Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects","volume":"20","author":"Anderson","journal-title":"Antivir Ther"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.115010","article-title":"Validation of an LC-MS\/MS assay for the simultaneous determination of bictegravir, doravirine, and raltegravir in human plasma","volume":"220","author":"Schauer","journal-title":"J Pharm Biomed Anal"},{"issue":"1","key":"R15","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1097\/QAI.0b013e31827fd47e","article-title":"Protein binding of lopinavir and ritonavir during 4 phases of pregnancy: implications for treatment guidelines","volume":"63","author":"Patterson","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"4","key":"R16","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02502-18","article-title":"Population pharmacokinetics of doravirine and exposure-response analysis in individuals with HIV-1","volume":"63","author":"Yee","journal-title":"Antimicrob Agents Chemother"}],"container-title":["JMIR Research Protocols"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.researchprotocols.org\/2026\/1\/e89990","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:24:32Z","timestamp":1785536672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchprotocols.org\/2026\/1\/e89990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":16,"URL":"https:\/\/doi.org\/10.2196\/89990","relation":{},"ISSN":["1929-0748"],"issn-type":[{"value":"1929-0748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"article-number":"v15i12e89990"}}