{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:59:41Z","timestamp":1777453181008,"version":"3.51.4"},"reference-count":18,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/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":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The GSK3732394 multivalent protein was developed as a novel, long-acting, antiretroviral biologic treatment regimen with three independent, non\u2013cross-resistant mechanisms for inhibiting HIV-1 entry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A single-centre, Phase 1, double-blind, randomized, placebo-controlled study was conducted in healthy volunteers, using a 2-part adaptive study design: in Part 1, participants were randomized to receive subcutaneous injection of GSK3732394 or placebo (3:1) as single ascending doses (10-mg starting dose); in Part 2, participants were intended to receive multiple ascending doses. Primary and secondary objectives included safety, pharmacokinetics (PK) and pharmacodynamics (PD; cluster of differentiation four receptor occupancy [CD4 RO]) of GSK3732394 in healthy adults; PK\/PD results in healthy volunteers were used to project HIV-1 treatment success.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The most frequently reported adverse event was injection site reactions (ISRs; 8\/18 [44%]). Most ISRs were mild (Grade 1\u20132; n = 7); one participant experienced a Grade 3 ISR (erythema \u226510\u00a0cm). All ISRs were delayed in onset (after Day 10). GSK3732394 demonstrated linear PK across all cohorts. Clearance was faster than expected, and PK\/PD results were lower than expected, with the maximum dose investigated (80\u00a0mg) achieving mean trough CD4 RO of \u223c25% on Day 7. The study was terminated as the PK\/PD model linking PK and CD4 RO indicated that the maximum planned doses would not achieve the desired therapeutic profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated successful deployment of PK\/PD dose relationships in the design and conduct of clinical trials by leveraging the findings toward predicting probability of success, resulting in appropriate early termination ( ClinicalTrials.gov , NCT03984812).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13596535221131164","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T13:53:40Z","timestamp":1664805220000},"page":"135965352211311","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["A Phase 1 randomized study of GSK3732394, an investigational long-acting biologic treatment regimen for HIV-1 infection"],"prefix":"10.1177","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-2584","authenticated-orcid":false,"given":"Mark","family":"Krystal","sequence":"first","affiliation":[{"name":"ViiV Healthcare, Branford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiven","family":"Chabria","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Branford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daren","family":"Austin","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen","family":"Wolstenholme","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wensel","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Branford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Lataillade","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Branford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judah","family":"Abberbock","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Upper Providence, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Baker","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Nyon, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Ackerman","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Branford, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"bibr1-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.17025"},{"key":"bibr2-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32832ba8ec"},{"key":"bibr3-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1007\/s12160-016-9827-3"},{"key":"bibr4-13596535221131164","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.16.3.18640"},{"key":"bibr5-13596535221131164","volume-title":"Cabenueva (Package Insert)","author":"ViiV Healthcare","year":"2022"},{"key":"bibr6-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00907-19"},{"key":"bibr7-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzq097"},{"key":"bibr8-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167395"},{"key":"bibr9-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00421-18"},{"key":"bibr10-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-015-0133-6"},{"key":"bibr11-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1711460"},{"key":"bibr12-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1086\/380802"},{"key":"bibr13-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1111\/dth.12817"},{"key":"bibr14-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjv096"},{"key":"bibr15-13596535221131164","first-page":"893","volume":"137","author":"Zeltser R","year":"2001","journal-title":"Arch Dermatol"},{"key":"bibr16-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2102131"},{"key":"bibr17-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.12.971"},{"key":"bibr18-13596535221131164","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00952.x"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13596535221131164","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13596535221131164","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13596535221131164","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:53:08Z","timestamp":1777380788000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.sagepub.com\/doi\/10.1177\/13596535221131164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1177\/13596535221131164"],"URL":"https:\/\/doi.org\/10.1177\/13596535221131164","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10]]}}}