{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T17:04:08Z","timestamp":1761239048523,"version":"3.37.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["212265\/Z\/18\/Z","203135\/Z\/16\/Z","214321\/B\/18\/Z","64787"],"award-info":[{"award-number":["212265\/Z\/18\/Z","203135\/Z\/16\/Z","214321\/B\/18\/Z","64787"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007112","name":"University of Cape Town","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007112","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1 AI068634","UM1 AI068636","UM1 AI106701"],"award-info":[{"award-number":["UM1 AI068634","UM1 AI068636","UM1 AI106701"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Dolutegravir concentrations are reduced by efavirenz induction effect necessitating twice-daily dolutegravir dosing when coadministered. Efavirenz induction persists for several weeks after stopping, which could potentially select for dolutegravir resistance if switching occurred with unsuppressed human immunodeficiency virus type 1 (HIV-1) RNA levels and standard dolutegravir dosing. We evaluated the need for a lead-in supplementary dolutegravir dose in adults failing first-line tenofovir-emtricitabine-efavirenz (TEE).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a randomized, double-blind, placebo-controlled, phase 2 trial in Khayelitsha, South Africa. Eligible patients had virologic failure (2 consecutive HIV-1 RNA \u22651000 copies\/mL) on first-line TEE. Participants were randomly assigned (1:1) to switch to tenofovir-lamivudine-dolutegravir (TLD) with a supplementary 50 mg dolutegravir dose or placebo taken 12 hours later for 14 days. Primary outcome was proportion with HIV-1 RNA &amp;lt;50 copies\/mL at week 24. This study was not powered to compare arms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>One hundred thirty participants were randomized (65 to each arm). Median baseline HIV-1 RNA was 4.0 log10 copies\/mL and 76% had baseline resistance to both tenofovir and lamivudine. One participant died and 2 were lost to follow-up. At week 24, 55 of 64 (86% [95% confidence interval {CI}: 75%\u201393%]) in the supplementary dolutegravir arm and 53 of 65 (82% [95% CI: 70%\u201390%]) in the placebo arm had HIV-1 RNA &amp;lt;50 copies\/mL. Grade 3 or 4 adverse events were similar in frequency between arms. None of 6 participants (3 in each arm) eligible for resistance testing by 24 weeks developed dolutegravir resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings do not support the need for initial dolutegravir dose adjustment in patients switching to TLD who failed first-line TEE.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT03991013.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciad023","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T17:49:35Z","timestamp":1673891375000},"page":"1832-1840","source":"Crossref","is-referenced-by-count":7,"title":["Initial Supplementary Dose of Dolutegravir in Second-Line Antiretroviral Therapy: A Noncomparative, Double-Blind, Randomized Placebo-Controlled Trial"],"prefix":"10.1093","volume":"76","author":[{"given":"Ying","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medicine"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3633-2878","authenticated-orcid":false,"given":"Rulan","family":"Griesel","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine"},{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaayid","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular 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Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3080-6606","authenticated-orcid":false,"given":"Gary","family":"Maartens","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine"},{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"author":"World Health 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