{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:09:37Z","timestamp":1776442177780,"version":"3.51.2"},"reference-count":23,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc."],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>To allow the continued participation of women enrolled in pre\u2010licensure clinical trials who become pregnant, and to potentially enrol pregnant women in clinical trials, non\u2010clinical developmental and reproductive toxicology studies (DART) are essential. Generally during pharmaceutical development, DART studies are conducted late during clinical development, leading to the exclusion of pregnant women from enrolment and withdrawal of women becoming pregnant during pre\u2010licensure trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Completing all DART studies prior to or early during the conduct of phase 3 trials (i.e. earlier than current common practice) can accelerate and facilitate the inclusion of women who become pregnant during pre\u2010licensure trials to remain on study drug and to potentially enrol pregnant women more rapidly. Promoting complementary strategies, such as alternative combinations of DART study designs and physiologically based pharmacokinetic modelling, could better inform drug dosing and safety in pregnancy at an earlier stage in drug development. The interpretation of the results of non\u2010clinical DART studies is often complex. Institutional review boards\/ethics committees should have access to relevant expertise for interpretation and application of results of non\u2010clinical developmental and reproductive toxicity studies. Clear communication and thorough understanding of non\u2010clinical findings and the overall benefit\u2013risk profile of the product are critical to review protocols and determine if women who become pregnant during a clinical trial could continue on study drug and\/or to enrol pregnant women in the trial. The informed consent document should be well written so that participants can make an informed decision to stay on study drug or participate in a trial during pregnancy. Ultimately, the decision to allow women who become pregnant during pre\u2010licensure trials to remain on study will depend on the totality of the evidence and benefit\u2013risk considerations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We propose that industry completes non\u2010clinical reproductive toxicity studies prior to or early during the conduct of phase 3 trials in HIV drug development, especially for priority agents, and potentially uses alternative DART study design strategies to achieve this goal.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25914","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T07:34:38Z","timestamp":1658216078000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Non\u2010clinical considerations for supporting accelerated inclusion of pregnant women in pre\u2010licensure clinical trials with anti\u2010HIV agents"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2599-7540","authenticated-orcid":false,"given":"Rick","family":"Greupink","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute of Molecular Life Sciences  Nijmegen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-2862","authenticated-orcid":false,"given":"Hedwig","family":"van Hove","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute of Molecular Life Sciences  Nijmegen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3294-3567","authenticated-orcid":false,"given":"Felix","family":"Mhlanga","sequence":"additional","affiliation":[{"name":"UZ\u2010UCSF Collaborative Study in Women's Health Zimbabwe  Harare Zimbabwe"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3766-1924","authenticated-orcid":false,"given":"Peter","family":"Theunissen","sequence":"additional","affiliation":[{"name":"CBG\u2010MEB  Utrecht Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0389-9934","authenticated-orcid":false,"given":"Angela","family":"Colbers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Radboud Institute for Health Sciences  Nijmegen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).ICH guideline M3(R2) on non\u2010clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals.2009. 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