{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T14:23:56Z","timestamp":1769351036467,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Long\u2010acting cabotegravir is approved for HIV treatment and prevention. To guide management of dosing deviations and interruptions, concentration\u2010time profiles for monthly and every 2 months regimens were simulated using a population pharmacokinetic (PPK) model. Adequate exposure was defined as trough concentration (C\n                    <jats:sub>tau<\/jats:sub>\n                    ) &gt;0.45\u00a0\u00b5g\/mL (observed 5th percentile of first C\n                    <jats:sub>tau<\/jats:sub>\n                    in pivotal studies) in &gt;95% of subjects and maximum concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ) &lt;13.1\u00a0\u00b5g\/mL (highest observed median steady\u2010state C\n                    <jats:sub>max<\/jats:sub>\n                    in previous studies) in &gt;50% of subjects. Simulations showed: (1) median C\n                    <jats:sub>max<\/jats:sub>\n                    remained \u22646.35\u00a0\u00b5g\/mL after doubled doses; (2) C\n                    <jats:sub>tau<\/jats:sub>\n                    was suboptimal after half dose at first injection but recovered with a corrective dose; (3) injection delays \u22647 days maintained adequate C\n                    <jats:sub>tau<\/jats:sub>\n                    , while longer delays caused extended low\u2010exposure periods (\u226423 days for 1\u2010month delay, \u226483 days for 3\u2010month delay); (4) reinitiating loading dose after delays &gt;1 month led to higher exposure than continuing injections and may mitigate efficacy loss and resistance risks; and (5) oral bridging (30\u00a0mg daily) maintained adequate exposure during delays. Recommended strategies include no action for higher\u2010than\u2010planned doses, corrective dosing for lower\u2010than\u2010planned doses, strict adherence to schedule, reinitiating the loading dose after delays &gt;1 month, and oral bridging. These findings were incorporated into product labeling and can inform next\u2010generation cabotegravir and other long\u2010acting agent development.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1568","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:08:38Z","timestamp":1752239318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Strategies to Manage Dosing Deviations and Interruptions of Cabotegravir Long\u2010Acting Intramuscular Injections"],"prefix":"10.1002","volume":"15","author":[{"given":"Kelong","family":"Han","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GSK  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald D.","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Clinical Development ViiV Healthcare  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Spreen","sequence":"additional","affiliation":[{"name":"Clinical Development ViiV Healthcare  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L.","family":"Ford","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling and Simulation GSK  Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-020-03055-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007161"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.16.3.18640"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000169"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.13451"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1310\/hct1405-192"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000301"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000365"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00152-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31917-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1909512"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1904398"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32666-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101016"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00538-4"},{"issue":"6","key":"e_1_2_8_18_1","doi-asserted-by":"crossref","DOI":"10.1128\/aac.01475-23","article-title":"Long\u2010acting cabotegravir pharmacokinetics with and without oral lead\u2010in for HIV PrEP","volume":"68","author":"Han K","year":"2024","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15439"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad370"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae620"},{"key":"e_1_2_8_22_1","unstructured":"RossenuS NeyensM Van Solingen\u2010RisteaR BaughB CrauwelsH.Population pharmacokinetic (PopPK) modeling and simulation of monthly intramuscular (im) long\u2010acting rilpivirine (RPV LA) to inform strategies following dosing interruptions in HIV\u20101 infected subjects. In:23rd International AIDS Conference. Abstract Number: PEB0264. 6\u201410 July 2020 Virtual.https:\/\/www.aids2020.org\/wp\u2010content\/uploads\/2020\/09\/AIDS2020_Abstracts.pdf"},{"key":"e_1_2_8_23_1","unstructured":"RossenuS NeyensM Van Solingen\u2010RisteaR BaughB CrauwelsH.PopPK modeling of Q2M IM RPV LA for managing dosing interruptions in HIV\u20101 patients. In:Conference on Retroviruses and Opportunistic Infections (CROI). Abstract Number: 403. 6\u201410 March 2021 Boston MA USA.https:\/\/www.croiwebcasts.org\/p\/2021croi\/croi\/403"},{"key":"e_1_2_8_24_1","unstructured":"HanK D'AmicoR SieversJ et\u00a0al.Phase I study of cabotegravir long\u2010acting injectable formulations supports \u22654\u2010monthly dose interval. In:Conference on Retroviruses and Opportunistic Infections (CROI). Abstract Number: 130. 3\u20106 March 2024 Denver CO USA.https:\/\/www.croiwebcasts.org\/p\/2024croi\/croi\/130"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00994-24"},{"key":"e_1_2_8_26_1","article-title":"Practical dosing guidance for the management of clinician\u2010administered injections of long\u2010acting cabotegravir and rilpivirine","volume":"10","author":"Patel P","year":"2023","journal-title":"Ther Adv Infect Dis"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1568","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1568","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1568","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T14:23:36Z","timestamp":1769264616000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cpdd.1568"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1568","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,11]]},"assertion":[{"value":"2025-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1568"}}