{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:18:35Z","timestamp":1789193915253,"version":"build-2803163510"},"reference-count":12,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>GSK3640254, a novel, next\u2010generation maturation inhibitor effective against a range of HIV polymorphisms with no cross\u2010resistance to current antiretroviral therapy, could potentially be coadministered with dolutegravir as a 2\u2010drug regimen. In this phase I study, pharmacokinetics and tolerability of GSK3640254 plus dolutegravir were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Healthy participants received dolutegravir 50\u00a0mg once daily (QD) on Days 1\u20135 in period 1, GSK3640254 200\u00a0mg QD on Days 1\u20137 in period 2, and dolutegravir 50\u00a0mg plus GSK3640254 200\u00a0mg QD on Days 1\u20137 in period 3. All treatments were administered with a moderate\u2010fat meal 30\u00a0minutes prior to dosing. Pharmacokinetics parameters were derived by noncompartmental methods, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were derived using linear mixed effects models. Adverse events, laboratory measurements, electrocardiography and vital signs were monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen participants completed the study. GMRs (90% CIs) for dolutegravir area under the plasma concentration\u2013time curve from time 0 to the end of the dosing interval at steady state, maximum observed concentration and plasma concentration at the end of the dosing interval were 1.17 (1.118\u20131.233), 1.09 (1.044\u20131.138) and 1.24 (1.160\u20131.315), respectively. The GMRs (90% CIs) for GSK3640254 were 1.04 (0.992\u20131.094), 0.99 (0.923\u20131.065) and 0.10 (0.939\u20131.056), respectively. Dolutegravir plus GSK3640254 coadministration did not meaningfully alter steady\u2010state exposure to dolutegravir or GSK3640254. No clinically significant trends in tolerability or safety were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Coadministration of GSK3640254 with dolutegravir did not result in clinically significant drug interaction and was well tolerated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14759","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T01:08:29Z","timestamp":1612573709000},"page":"3501-3507","source":"Crossref","is-referenced-by-count":15,"title":["Phase I evaluation of pharmacokinetics and tolerability of the HIV\u20101 maturation inhibitor GSK3640254 and dolutegravir in healthy adults"],"prefix":"10.1111","volume":"87","author":[{"given":"Teodora","family":"Pene Dumitrescu","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samit R.","family":"Joshi","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Greene","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Johnson","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Butcher","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"PPD  Richmond VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Webster","sequence":"additional","affiliation":[{"name":"PPD  Richmond VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa T.","family":"Pham","sequence":"additional","affiliation":[{"name":"PPD  Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Lataillade","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherene","family":"Min","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007161"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205368"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728220903039714"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2015.05.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328331c83b"},{"key":"e_1_2_10_7_1","unstructured":"DeJesusE JohnsonM DumontE et al.A phase IIa study of novel maturation inhibitor GSK2838232 in HIV patients. 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