{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:43:41Z","timestamp":1790232221598,"version":"4.1.0"},"reference-count":23,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Long-acting cabotegravir is approved for pre-exposure prophylaxis and combination HIV treatment, both initiated with optional short-term oral lead-in (OLI). We evaluated the impact of OLI on long-acting cabotegravir pharmacokinetics. Cabotegravir plasma concentrations were compared between HIV-positive participants initiating injections with (\n n<\/jats:italic>\n = 278) or without (\n n<\/jats:italic>\n = 110) OLI in phase III treatment study FLAIR and in HIV-negative participants using OLI (\n n<\/jats:italic>\n = 263) in pivotal pre-exposure prophylaxis studies HPTN 083 and HPTN 084. Cabotegravir pharmacokinetic profiles were simulated in three populations (assigned-male-at-birth, 50%-assigned-female-at-birth, and assigned-female-at-birth) under three scenarios: first injection given (A) 1 or (B) 3 days after final OLI dose (OLI-injection gap) or (C) without OLI. The PK objective was 80% of participants achieving 4\u00d7\n in vitro<\/jats:italic>\n protein-adjusted 90% maximal inhibitory concentration (PA-IC\n 90<\/jats:sub>\n ) and 50% achieving 8\u00d7 PA-IC\n 90<\/jats:sub>\n . Observed trough concentrations (\n C<\/jats:italic>\n \u03c4<\/jats:sub>\n ) were similar with and without OLI (\n P<\/jats:italic>\n > 0.3). With a 3-day OLI-injection gap, simulated pre-injection\n C<\/jats:italic>\n \u03c4<\/jats:sub>\n remained above PK objective. Approximately 1\u20132 weeks after the first injection, simulated PK profiles became nearly identical among all scenarios. Without OLI, it was predicted that 80% of participants achieve 4\u00d7 PA-IC\n 90<\/jats:sub>\n in 1.2, 1.8, and 2.8 days after the first injection in each population, respectively, and 50% achieve 8\u00d7 PA-IC\n 90<\/jats:sub>\n in 1.4, 2.1, and 3.8 days, respectively. Observed long-acting cabotegravir exposure was similar with or without OLI, supporting optional OLI use. Cabotegravir exposure was predicted to remain above PK objective for OLI-injection gaps of \u22643 days and rapidly achieve PK objective after first injection without OLI. Findings are consistent between assigned-male-at-birth and assigned-female-at-birth populations.\n <\/jats:p>\n \n This study is registered with\n ClinicalTrials.gov<\/jats:ext-link>\n as\n NCT02720094<\/jats:ext-link>\n .\n \n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/aac.01475-23","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T12:49:43Z","timestamp":1714999783000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Long-acting cabotegravir pharmacokinetics with and without oral lead-in for HIV PrEP"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8010-9898","authenticated-orcid":true,"given":"Kelong","family":"Han","sequence":"first","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parul","family":"Patel","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"McCallister","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Branford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex R.","family":"Rinehart","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Gandhi","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Spreen","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael J.","family":"Landovitz","sequence":"additional","affiliation":[{"name":"Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinead","family":"Delany-Moretlwe","sequence":"additional","affiliation":[{"name":"Wits RHI, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-8786","authenticated-orcid":true,"given":"Mark A.","family":"Marzinke","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"McKeon","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Budnik","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Brentford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"van Wyk","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Brentford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Ford","sequence":"additional","affiliation":[{"name":"GSK, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00056-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506273"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101016"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00538-4"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1017\/jme.2022.30"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007161"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.16.3.18640"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000169"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.13451"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000168"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31917-7"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32666-0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1904398"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1909512"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab439"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02057-21"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15439"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01005-1"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1248707"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010298"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(21)00184-3"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14980"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002690"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01475-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01475-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T12:49:52Z","timestamp":1714999792000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01475-23"}},"subtitle":[],"editor":[{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,6]]},"references-count":23,"alternative-id":["10.1128\/aac.01475-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01475-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,6]]},"assertion":[{"value":"2023-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01475-23"}}