{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:10:56Z","timestamp":1787991056941,"version":"build-2784847793"},"reference-count":10,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2\/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52\u00a0weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated. Genotypic and phenotypic resistance to LEN was evaluated for subjects with virological failure through Week 52.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, viruses with resistance to EIs showed no cross-resistance to LEN, with a mean fold change from wild type close to 1.0. Of the 22 participants analysed for resistance through Week 52, 9 participants (13%) had emergence of capsid resistance mutation(s) while the remaining 13 participants (18%) had no change in the capsid sequence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The gag sequence from EI-resistant isolates did not affect LEN susceptibility. The lack of cross-resistance to LEN across ARV-resistant isolates supports the use of LEN in PWH regardless of their treatment history. During the second half-year period of the CAPELLA Study, development of LEN resistance was rare and was overall associated with functional LEN monotherapy due to either nonadherence or resistance-driven non-susceptibility to OBR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13596535231220754","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T12:39:04Z","timestamp":1702384744000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA"],"prefix":"10.1177","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0911-4237","authenticated-orcid":false,"given":"Nicolas","family":"Margot","sequence":"first","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-8715","authenticated-orcid":false,"given":"Nina","family":"Pennetzdorfer","sequence":"additional","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidula","family":"Naik","sequence":"additional","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rhee","sequence":"additional","affiliation":[{"name":"Clinical Research, Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Callebaut","sequence":"additional","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"bibr1-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2443-1"},{"key":"bibr2-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2115542"},{"key":"bibr3-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(23)00113-3"},{"key":"bibr4-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac364"},{"key":"bibr5-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.13288"},{"key":"bibr6-13596535231220754","first-page":"151","volume":"2","author":"Ray N","year":"2009","journal-title":"Drug Des Dev Ther"},{"key":"bibr7-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000001602"},{"key":"bibr8-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00942-08"},{"key":"bibr9-13596535231220754","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa060"},{"key":"bibr10-13596535231220754","unstructured":"Yant SR, Mulato A, Hansen D, et al. In vitro resistance profile of GS-6207, a first-in-class picomolar HIV capsid inhibitor in clinical development as a novel long-acting antiretroviral agent [abstract no. TUPE075]. In: 10th IAS conference on HIV science (IAS 2019), Mexico City, Mexico, 21\u201324 July 2019."}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13596535231220754","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13596535231220754","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13596535231220754","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:53:13Z","timestamp":1777380793000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13596535231220754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1177\/13596535231220754"],"URL":"https:\/\/doi.org\/10.1177\/13596535231220754","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12]]},"article-number":"13596535231220754"}}