{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:59Z","timestamp":1792785959075,"version":"4.5.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Pharmacometrics Africa NPC"},{"DOI":"10.13039\/501100001321","name":"The National Research Foundation","doi-asserted-by":"crossref","award":["109056"],"award-info":[{"award-number":["109056"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"crossref"}]},{"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":[],"published-print":{"date-parts":[[2021,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In sub-Saharan Africa, artemisinin-containing therapies for malaria treatment are regularly co-administered with ART. Currently, dolutegravir-based regimens are recommended as first-line therapy for HIV across most of Africa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the population pharmacokinetics of dolutegravir during co-administration with artemether\/lumefantrine or artesunate\/amodiaquine, two commonly used antimalarial therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a population pharmacokinetic model of dolutegravir with data from 26 healthy volunteers in two Phase 2 studies with a total of 403 dolutegravir plasma concentrations at steady state. Volunteers received 50\u2009mg of dolutegravir once daily alone or in combination with standard treatment doses of artemether\/lumefantrine (80\/480\u2009mg) or artesunate\/amodiaquine (200\/540\u2009mg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A two-compartment model with first-order elimination and transit compartment absorption best described the concentration\u2013time data of dolutegravir. Typical population estimates for clearance, absorption rate constant, central volume, peripheral volume and mean absorption transit time were 0.713\u2009L\/h, 1.68\u2009h\u22121, 13.2\u2009L, 5.73\u2009L and 1.18\u2009h, respectively. Co-administration of artemether\/lumefantrine or artesunate\/amodiaquine increased dolutegravir clearance by 10.6% (95% CI 4.09%\u201334.5%) and 26.4% (95% CI 14.3%\u201351.4%), respectively. Simulations showed that simulated trough concentrations of dolutegravir alone or in combination with artemether\/lumefantrine or artesunate\/amodiaquine are maintained above the dolutegravir protein-adjusted IC90 of 0.064\u2009mg\/L for more than 99% of the individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dolutegravir dose adjustments are not necessary for patients who are taking standard 3\u2009day treatment doses of artemether\/lumefantrine or artesunate\/amodiaquine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkab022","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T07:26:45Z","timestamp":1610954805000},"page":"1269-1272","source":"Crossref","is-referenced-by-count":10,"title":["Dolutegravir pharmacokinetics during co-administration with either artemether\/lumefantrine or artesunate\/amodiaquine"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7975-0178","authenticated-orcid":false,"given":"Aida N","family":"Kawuma","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Infectious Diseases Institute, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen I","family":"Walimbwa","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goonaseelan (Colin)","family":"Pillai","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"CP+ Associates GmbH, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saye","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Lamorde","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5769-8150","authenticated-orcid":false,"given":"Roeland E","family":"Wasmann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"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, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,7]]},"reference":[{"key":"2021041609050996600_dkab022-B1","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1007\/s10900-012-9559-7","article-title":"Severity of outcomes associated to types of HIV coinfection with TB and malaria in a setting where the three pandemics overlap","volume":"37","author":"Tshikuka Mulumba","year":"2012","journal-title":"J Community 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