{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:48:53Z","timestamp":1788407333752,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>HIV prevention with pre\u2010exposure prophylaxis (PrEP) constitutes a major pillar in fighting the ongoing epidemic. While daily oral PrEP adherence may be challenging, long\u2010acting (LA\u2010)PrEP in oral or implant formulations could overcome frequent dosing with convenient administration. The novel drug islatravir (ISL) may be suitable for LA\u2010PrEP, but dose\u2010dependent reductions in  T cell and lymphocyte counts were observed at high doses. We developed a mathematical model to predict ISL pro\u2010drug levels in plasma and active intracellular ISL\u2010triphosphate concentrations after oral vs. subcutaneous implant dosing. Using phase II trial data, we simulated antiviral effects and estimated HIV risk reduction for multiple dosages and dosing frequencies. We then established exposure thresholds where no adverse effects on immune cells were observed. Our findings suggest that implants with 56\u201362\u2009mg ISL offer effective HIV risk reduction without reducing lymphocyte counts. Oral 0.1\u2009mg daily, 3\u20135\u2009mg weekly, and 10\u2009mg biweekly ISL provide comparable efficacy, but weekly and biweekly doses may affect lymphocyte counts, while daily dosing regimen offered no advantage over existing oral PrEP. Oral 0.5\u20131\u2009mg on demand provided  protection, while not being suitable for post\u2010exposure prophylaxis. These findings suggest ISL could be considered for further development as a promising and safe agent for implantable PrEP.<\/jats:p>","DOI":"10.1002\/psp4.13212","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T02:37:00Z","timestamp":1724294220000},"page":"1693-1706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Modeling of HIV\u20101 prophylactic efficacy and toxicity with islatravir shows non\u2010superiority for oral dosing, but\u00a0promise as a subcutaneous implant"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9060-8953","authenticated-orcid":false,"given":"Hee\u2010yeong","family":"Kim","sequence":"first","affiliation":[{"name":"Project Group 5 \u201cSystems Medicine of Infectious Disease\u201d Robert Koch Institute  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-4450","authenticated-orcid":false,"given":"Lanxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Project Group 5 \u201cSystems Medicine of Infectious Disease\u201d Robert Koch Institute  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5696-8665","authenticated-orcid":false,"given":"Craig W.","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-3190","authenticated-orcid":false,"given":"Jessica E.","family":"Haberer","sequence":"additional","affiliation":[{"name":"Center for Global Health Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-6394","authenticated-orcid":false,"given":"Max","family":"von Kleist","sequence":"additional","affiliation":[{"name":"Project Group 5 \u201cSystems Medicine of Infectious Disease\u201d Robert Koch Institute  Berlin Germany"},{"name":"Mathematics for Data Science, Department of Mathematics and Computer Science Freie Universit\u00e4t Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6189183"},{"key":"e_1_2_9_3_1","volume-title":"Virus Hunting: AIDS, Cancer, and the Human Retrovirus: A Story of Scientific Discovery","author":"Gallo RC","year":"1991"},{"key":"e_1_2_9_4_1","unstructured":"Fact sheet \u2013 Latest global and regional statistics on the status of the AIDS epidemic.https:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/UNAIDS_FactSheet_en.pdf. 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