{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:12:03Z","timestamp":1782904323376,"version":"3.54.5"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              A fixed-dose combination (FDC) of 50 mg dolutegravir and 300 mg lamivudine is indicated for the treatment of HIV-1 infection. This analysis aimed to characterize the population pharmacokinetics (PK) of dolutegravir and lamivudine based on data from a phase 3 study (TANGO) in virologically suppressed adults living with HIV-1 switching to dolutegravir\/lamivudine FDC. These analyses included 362 participants who contributed 2,629 dolutegravir and 2,611 lamivudine samples collected over 48 weeks. A one-compartment model with first-order absorption and elimination parameterized by apparent oral clearance (CL\/F), apparent volume of distribution (V\/F), and absorption rate constant (Ka) described dolutegravir PK. Covariate search yielded body weight, bilirubin, and ethnicity as predictors of CL\/F, and weight was predictive for V\/F. The estimates of CL\/F, V\/F, and Ka were 0.858 L\/h, 16.7 L, and 2.15 h\n              <jats:sup>\u22121<\/jats:sup>\n              , respectively. A two-compartment model with first-order absorption and elimination parameterized by CL\/F, apparent intercompartmental clearance (Q\/F), apparent central volume of distribution (V2\/F), apparent peripheral volume of distribution (V3\/F), and Ka described lamivudine PK. Covariate search yielded eGFR and race as predictors of CL\/F, and weight was predictive for V2\/F. The estimated parameter values were CL\/F = 19.6 L\/h, Q\/F = 2.97 L\/h, V2\/F = V3\/F = 105 L, and Ka = 2.30 h\n              <jats:sup>\u22121<\/jats:sup>\n              . The steady-state prediction suggested that the effect of covariates dolutegravir and lamivudine exposures was small (&lt;20%) and not clinically relevant. Therefore, no dose adjustments are recommended based on these analyses. The results support the use of dolutegravir\/lamivudine FDC in the treatment of HIV-1 infection in adults.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>CLINICAL TRIALS<\/jats:title>\n              <jats:p>\n                This study is registered with\n                <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/\" xlink:type=\"simple\">ClinicalTrials.gov<\/jats:ext-link>\n                as\n                <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03446573\" xlink:type=\"simple\">NCT03446573<\/jats:ext-link>\n                .\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aac.01504-23","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T13:00:41Z","timestamp":1712581241000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Population pharmacokinetic modeling of dolutegravir\/lamivudine to support a once-daily fixed-dose combination regimen in virologically suppressed adults living with HIV-1"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1289-0800","authenticated-orcid":false,"given":"Hardik","family":"Chandasana","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modeling &amp; Simulation, GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Singh","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling &amp; Simulation, GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Adkison","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mounir","family":"Ait-Khaled","sequence":"additional","affiliation":[{"name":"ViiV Healthcare Ltd., Brentford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-2653","authenticated-orcid":false,"given":"Teodora","family":"Pene Dumitrescu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling &amp; Simulation, GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.35"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12716"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.18683\/germs.2017.1115"},{"key":"e_1_3_5_6_2","unstructured":"DOVATO (dolutegravir and lamivudine) [package insert]. 2021. ViiV Healthcare Research Triangle Park NC. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/211994s011lbl.pdf."},{"key":"e_1_3_5_7_2","unstructured":"DOVATO (dolutegravir and lamivudine) [package leaflet]. 2021. ViiV Healthcare Brentford United Kingdom. https:\/\/www.medicines.org.uk\/emc\/files\/pil.10446.pdf."},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32462-0"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002275"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.740"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz1243"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12639"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.12.3025"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-009-9112-1"},{"key":"e_1_3_5_15_2","unstructured":"TIVICAY (dolutegravir) [package insert]. 2021. ViiV Healthcare Research Triangle Park NC. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/204790s028 213983s002lbl.pdf."},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140090-00005"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32834a1dd9"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90183-6"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.6.1514"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01504-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01504-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T13:04:32Z","timestamp":1714655072000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01504-23"}},"subtitle":[],"editor":[{"given":"Sean","family":"Wasserman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,2]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,2]]}},"alternative-id":["10.1128\/aac.01504-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01504-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,2]]},"assertion":[{"value":"2023-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01504-23"}}