{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:57:56Z","timestamp":1790783876123,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences, Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <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 in clinical development for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) harboring multidrug resistance (MDR) in combination with an optimized background regimen (OBR). Here we describe resistance analyses conducted in the pivotal phase 2\/3 CAPELLA study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>CAPELLA enrolled viremic HTE PWH with resistance to \u22653 of 4 of the main antiretroviral (ARV) classes and resistance to \u22652 ARV drugs per class. Baseline resistance analyses used commercial assays (HIV-1 protease, reverse transcriptase, integrase genotypic\/phenotypic tests). Postbaseline resistance was evaluated in participants experiencing virologic failure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At baseline, 46% of participants had resistance to the 4 main ARV drug classes, with one-third of participants having exhausted all drugs from \u22653 of the 4 main ARV classes. Treatment with LEN + OBR for 26\u2005weeks led to viral suppression in 81% of participants. Postbaseline resistance mutations to lenacapavir occurred in 8 participants (6 with M66I, 1 with K70H, 1 with Q67H + K70R) who were receiving unintended functional LEN monotherapy at the time of resistance selection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>LEN added to OBR led to high efficacy in this HTE patient population with MDR but could select for resistance when used unintentionally as functional monotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiac364","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T12:34:47Z","timestamp":1662726887000},"page":"1985-1991","source":"Crossref","is-referenced-by-count":62,"title":["Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir"],"prefix":"10.1093","volume":"226","author":[{"given":"Nicolas A","family":"Margot","sequence":"first","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidula","family":"Naik","sequence":"additional","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"VanderVeen","sequence":"additional","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Anoshchenko","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Singh","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Dvory-Sobol","sequence":"additional","affiliation":[{"name":"Clinical Research, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S","family":"Rhee","sequence":"additional","affiliation":[{"name":"Clinical Research, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Callebaut","sequence":"additional","affiliation":[{"name":"Clinical Virology, Gilead Sciences, Inc , Foster City, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"2022112816393378100_jiac364-B1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/s41586-020-2443-1","article-title":"Clinical targeting of HIV capsid protein with a long-acting small molecule","volume":"584","author":"Link","year":"2020","journal-title":"Nature"},{"key":"2022112816393378100_jiac364-B2","doi-asserted-by":"crossref","first-page":"e02057\u201320","DOI":"10.1128\/AAC.02057-20","article-title":"Absence of lenacapavir (GS-6207) phenotypic resistance in HIV gag cleavage site mutants and in isolates with resistance to existing drug classes","volume":"65","author":"Margot","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2022112816393378100_jiac364-B3","author":"Margot","year":"2022"},{"key":"2022112816393378100_jiac364-B4","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/jac\/dkab503","article-title":"Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study","volume":"77","author":"Margot","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2022112816393378100_jiac364-B5","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1093\/jac\/dkaa060","article-title":"Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients","volume":"75","author":"Marcelin","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2022112816393378100_jiac364-B6","author":"Begley","year":"2020"},{"key":"2022112816393378100_jiac364-B7","author":"Daar","year":"2020"},{"key":"2022112816393378100_jiac364-B8","author":"Gupta","year":"2021"},{"key":"2022112816393378100_jiac364-B9","author":"Segal-Maurer","year":"2021"},{"key":"2022112816393378100_jiac364-B10","author":"Molina","year":"2021"},{"key":"2022112816393378100_jiac364-B11","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1056\/NEJMoa2115542","article-title":"Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 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