{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:17:19Z","timestamp":1793146639147,"version":"4.5.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"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":[[2022,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>GSK3640254 (GSK\u2019254) is a next-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor with pharmacokinetics (PK) supporting once-daily therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This phase IIa double-blind (sponsor-unblinded), randomized, placebo-controlled, adaptive study evaluated antiviral effect, safety, tolerability, and PK of once-daily GSK\u2019254 monotherapy administered with food (moderate-fat meal) in HIV-1\u2013positive, treatment-naive adults. In part 1, participants received GSK\u2019254 10 or 200 mg for 10 days. In part 2, participants received GSK\u2019254 40, 80, or 140 mg for 7 days, modified from 10 days by a protocol amendment to decrease potential for resistance-associated mutations (RAMs). The primary endpoint was maximum change from baseline in HIV-1 RNA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Maximum changes in HIV-1 RNA of\u2005\u22120.4, \u22121.2, \u22121.0, \u22121.5, and\u2005\u22122.0 log10 occurred with GSK\u2019254 10, 40, 80, 140, and 200 mg, respectively. Regardless of dosing duration, doses\u2005\u226540 mg resulted in\u2005\u22651-log10 declines in HIV-1 RNA. Plasma PK was generally dose proportional to 140 mg but non-proportional between 140 and 200 mg. Four participants in the 200-mg group developed RAMs on day 11 in part 1, 1 with phenotypic resistance. No RAMs occurred in part 2. Adverse events (AEs) were reported by 22 (65%) participants; headache was the most common (n\u2005=\u20054). Two non\u2013drug-related serious AEs occurred. All AEs were of mild-to-moderate intensity, except for 2 grade 3 non\u2013drug-related AEs in 1 participant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This monotherapy study established a dose\u2013antiviral response relationship for GSK\u2019254. No safety or tolerability concerns were noted. These results supported dose selection for the ongoing phase IIb study (ClinicalTrials.gov: NCT04493216).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT03784079.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab1065","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T20:14:31Z","timestamp":1641413671000},"page":"786-794","source":"Crossref","is-referenced-by-count":22,"title":["Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254"],"prefix":"10.1093","volume":"75","author":[{"given":"Christoph D","family":"Spinner","sequence":"first","affiliation":[{"name":"Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II , Munich , 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