{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:49:46Z","timestamp":1792500586673,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We evaluated the pharmacokinetics of tenofovir alafenamide fumarate (TAF) and tenofovir in a subset of African children enrolled in the CHAPAS-4 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Children aged 3\u201315 years with human immunodeficiency virus infection failing first-line antiretroviral therapy were randomized to emtricitabine\/TAF versus standard-of-care nucleoside reverse transcriptase inhibitor combination, plus dolutegravir, atazanavir\/ritonavir, darunavir\/ritonavir, or lopinavir\/ritonavir. Daily emtricitabine\/TAF was dosed according to World Health Organization (WHO)\u2013recommended weight bands: 120\/15 mg in children weighing 14 to &amp;lt;25 kg and 200\/25 mg in those weighing \u226525 kg. At steady state, 8\u20139 blood samples were taken to construct pharmacokinetic curves. Geometric mean (GM) area under the concentration\u2013time curve (AUC) and the maximum concentration (Cmax) were calculated for TAF and tenofovir and compared to reference exposures in adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pharmacokinetic results from 104 children taking TAF were analyzed. GM (coefficient of variation [CV%]) TAF AUClast when combined with dolutegravir (n = 18), darunavir\/ritonavir (n = 34), or lopinavir\/ritonavir (n = 20) were 284.5 (79), 232.0 (61), and 210.2 (98) ng*hour\/mL, respectively, and were comparable to adult reference values. When combined with atazanavir\/ritonavir (n = 32), TAF AUClast increased to 511.4 (68) ng*hour\/mL. For each combination, tenofovir GM (CV%) AUCtau and Cmax remained below reference values in adults taking 25 mg TAF with a boosted protease inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In children, TAF combined with boosted PIs or dolutegravir and dosed according to WHO-recommended weight bands provides TAF and tenofovir concentrations previously demonstrated to be well tolerated and effective in adults. These data provide the first evidence for use of these combinations in African children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>ISRCTN22964075.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciad267","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T19:59:20Z","timestamp":1684958360000},"page":"875-882","source":"Crossref","is-referenced-by-count":16,"title":["First Pharmacokinetic Data of Tenofovir Alafenamide Fumarate and Tenofovir With Dolutegravir or Boosted Protease Inhibitors in African Children: A Substudy of the CHAPAS-4 Trial"],"prefix":"10.1093","volume":"77","author":[{"given":"Hylke","family":"Waalewijn","sequence":"first","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 , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roeland E","family":"Wasmann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-8699","authenticated-orcid":false,"given":"Lubbe","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chishala","family":"Chabala","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, School of Medicine, University of Zambia"},{"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"},{"name":"Department of Paediatrics and Child Health, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara N","family":"Monkiewicz","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair","family":"Bamford","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London , United Kingdom"},{"name":"Infection, Immunity & Inflammation Department, UCL Great Ormond Street Institute of Child Health , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Doerholt","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London , United Kingdom"},{"name":"Paediatric Infectious Diseases Unit, St George's University Hospital , London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-079X","authenticated-orcid":false,"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , South Africa"}],"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 , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , South Africa"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0389-9934","authenticated-orcid":false,"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"}]},{"name":"for the Children with HIV in Africa \u2013 Pharmacokinetics and Acceptability of Simple second-line antiretroviral regimens (CHAPAS-4) Trial 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