{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:42Z","timestamp":1788454842446,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001336","name":"University of the Witwatersrand, Johannesburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Dolutegravir is associated with more weight gain than efavirenz in people starting antiretroviral therapy (ART). We investigated the concentration\u2013response relationships of efavirenz and dolutegravir with weight gain. We determined concentration\u2013response relationships of dolutegravir and efavirenz (both combined with tenofovir disoproxil fumarate and emtricitabine) with changes in weight and fat distribution, derived from dual\u2010energy x\u2010ray absorptiometry scans, in a nested study of ART\u2010na\u00efve participants from a randomised controlled trial. Pharmacokinetic parameters used in analyses were efavirenz mid\u2010dosing interval concentrations and estimated dolutegravir area under the concentration\u2013time curve using a population pharmacokinetic model developed in the study population. Study outcomes were percentage changes from baseline to week 48 in weight, and visceral and subcutaneous adipose tissue mass. Pharmacokinetic data were available for 158 and 233 participants in the efavirenz arm and dolutegravir arms respectively; 57.0% were women. On multivariable linear regression there were independent negative associations between efavirenz concentrations and changes in both weight (<jats:italic>P\u2009&lt;<\/jats:italic>\u00a0.001) and subcutaneous adipose tissue mass (<jats:italic>P\u2009=<\/jats:italic>\u00a0.002). Estimated dolutegravir area under the concentration\u2013time curve up to 24 hours was not associated with change in weight (<jats:italic>P\u2009=<\/jats:italic>\u00a0.109) but was negatively associated with change in visceral adipose tissue mass (<jats:italic>P\u2009=<\/jats:italic>\u00a0.025). We found an independent negative concentration\u2013response relationship between efavirenz concentrations and weight change in ART\u2010na\u00efve participants. Dolutegravir concentrations were not independently associated with weight change. These findings suggest that weight gain differences between efavirenz and dolutegravir are driven by efavirenz toxicity impairing weight gain rather than by off\u2010target effects of dolutegravir causing weight gain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15177","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:44:25Z","timestamp":1640565865000},"page":"883-893","source":"Crossref","is-referenced-by-count":19,"title":["Concentration\u2013response relationships of dolutegravir and efavirenz with weight change after starting antiretroviral therapy"],"prefix":"10.1111","volume":"88","author":[{"given":"Rulan","family":"Griesel","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida N.","family":"Kawuma","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\/0000-0002-5769-8150","authenticated-orcid":false,"given":"Roeland","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"}]},{"given":"Simiso","family":"Sokhela","sequence":"additional","affiliation":[{"name":"Ezintsha, Wits Reproductive Health and HIV Institute, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godspower","family":"Akpomiemie","sequence":"additional","affiliation":[{"name":"Ezintsha, Wits Reproductive Health and HIV Institute, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. D. Francois","family":"Venter","sequence":"additional","affiliation":[{"name":"Ezintsha, Wits Reproductive Health and HIV Institute, Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubbe","family":"Wiesner","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"}]},{"given":"Phumla","family":"Sinxadi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3080-6606","authenticated-orcid":false,"given":"Gary","family":"Maartens","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz999"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30238-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902824"},{"key":"e_1_2_11_5_1","unstructured":"European Medicines Agency.Assessment report. Dolutegravir (Tivicay). (Available at:https:\/\/www.ema.europa.eu\/documents\/assessment\u2010report\/tivicay\u2010epar\u2010public\u2010assessment\u2010report_en.pdf[accessed March 2021])."},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2055-6640(20)30277-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706929"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2016.05.013"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24459"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000606"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32835a450b"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1219"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1073"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/003591576505800503"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12934"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2011.367"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002650"},{"issue":"1","key":"e_1_2_11_18_1","first-page":"1","article-title":"HIV and antiretroviral therapy\u2010related fat alterations","volume":"6","author":"Koethe JR","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32832b4377"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/589622"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30241-1"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01457-y"},{"issue":"2","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0229617","article-title":"Lack of an association between clinical INSTI\u2010related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight","volume":"15","author":"McMahon C","year":"2020","journal-title":"PLoS ONE"},{"key":"e_1_2_11_24_1","unstructured":"BurdetC PeytavinG LeM et al.Drug concentrations and body gain in PLWH switched to 3TC and dolutegravir. Poster presented at: CROI;2020; Boston Massachusetts. Abstract 677."},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02532-14"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328360dbb4"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15177","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.15177","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T14:28:21Z","timestamp":1692973701000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/bcp.15177"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15177","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]}}}