{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:18:36Z","timestamp":1789193916656,"version":"build-2803163510"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000765","name":"University College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC core funding","award":["MC_UU_00004\/03"],"award-info":[{"award-number":["MC_UU_00004\/03"]}]},{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["TRIA2015-1078"],"award-info":[{"award-number":["TRIA2015-1078"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Dolutegravir (DTG), combined with a backbone of 2 nucleoside reverse transcriptase inhibitors, is currently the preferred first-line treatment for human immunodeficiency virus (HIV) in childhood. CHAPAS4 is an ongoing randomized controlled trial investigating second-line treatment options for children with HIV. We did a nested pharmacokinetic (PK) substudy within CHAPAS4 to evaluate the DTG exposure in children with HIV taking DTG with food as part of their second-line treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Additional consent was required for children on DTG enrolled in the CHAPAS4 trial to participate in this PK substudy. Children weighing 14\u201319.9 kg took 25 mg DTG as dispersible tablets and children \u226520 kg took 50 mg film-coated tablets. Steady-state 24-hour DTG plasma concentration-time PK profiling was done at t = 0 and 1, 2, 4, 6, 8, 12, and 24 hours after observed DTG intake with food. Reference adult PK data and pediatric data from the ODYSSEY trial were used primarily for comparison. The individual target trough concentration (Ctrough) was defined as 0.32 mg\/L.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-nine children on DTG were included in this PK substudy. The geometric mean (GM) area under the concentration\u2013time curve over the dosing interval (AUC0-24h) was 57.1 hours \u00d7 mg\/L (coefficient of variation [CV%], 38.4%), which was approximately 8% below the average AUC0-24h in children in the ODYSSEY trial with comparable dosages, but above the adult reference. The GM (CV%) Ctrough was 0.82 mg\/L (63.8%), which was comparable to ODYSSEY and adult reference values.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This nested PK substudy shows that the exposure of DTG taken with food in children on second-line treatment is comparable with that of children in the ODYSSEY trial and adult references.<\/jats:p>\n                  <jats:p>Clinical Trials Registration.ISRCTN22964075.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciad346","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T13:56:00Z","timestamp":1686318960000},"page":"1312-1317","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacokinetic Data of Dolutegravir in Second-line Treatment of Children With Human Immunodeficiency Virus: Results From the CHAPAS4 Trial"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3699-2993","authenticated-orcid":false,"given":"Lisanne A H","family":"Bevers","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hylke","family":"Waalewijn","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen , The Netherlands"},{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Szubert","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chishala","family":"Chabala","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, University Teaching Hospital , Lusaka , Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsa","family":"Bwakura-Dangarembizi","sequence":"additional","affiliation":[{"name":"University of Zimbabwe Clinical Research Centre , Harare"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafic","family":"Makumbi","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre, Mbarara Regional Centre of Excellence , Mbarara , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Nangiya","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre, Research Department , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Mumbiro","sequence":"additional","affiliation":[{"name":"University of Zimbabwe Clinical Research Centre , Harare"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Mulenga","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, University Teaching Hospital , Lusaka , Zambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Musiime","sequence":"additional","affiliation":[{"name":"Joint Clinical Research Centre, Research Department , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M","family":"Gibb","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Colbers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"2024021012504336300_ciad346-B1","author":"Joint United Nations Programme on HIV\/AIDS","year":"2021"},{"key":"2024021012504336300_ciad346-B2","author":"Joint United Nations Programme on HIV\/AIDS","year":"2022"},{"key":"2024021012504336300_ciad346-B3","author":"World Health Organization 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children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial","volume":"9","author":"Turkova","year":"2022","journal-title":"Lancet HIV"},{"key":"2024021012504336300_ciad346-B7","doi-asserted-by":"crossref","first-page":"e341","DOI":"10.1016\/S2352-3018(21)00292-7","article-title":"Dolutegravir dosing for children with HIV weighing less than 20 kg: pharmacokinetic and safety substudies nested in the open-label, multicentre, randomised, non-inferiority ODYSSEY trial","volume":"9","author":"Waalewijn","year":"2022","journal-title":"Lancet HIV"},{"key":"2024021012504336300_ciad346-B8","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1128\/AAC.05739-11","article-title":"Effect of food on the pharmacokinetics of the integrase inhibitor dolutegravir","volume":"56","author":"Song","year":"2012","journal-title":"Antimicrob Agents 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adults","volume":"25","author":"Min","year":"2011","journal-title":"AIDS"},{"key":"2024021012504336300_ciad346-B12","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1093\/infdis\/jis750","article-title":"Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING study","volume":"207","author":"Eron","year":"2013","journal-title":"J Infect Dis"},{"key":"2024021012504336300_ciad346-B13","author":"ViiV Healthcare","year":"2013"},{"key":"2024021012504336300_ciad346-B14","author":"US Food and Drug Administration","year":"2015"}],"container-title":["Clinical Infectious 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