{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:56:06Z","timestamp":1792454166679,"version":"4.5.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Gilead Sciences, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lenacapavir is a highly potent first-in-class inhibitor of HIV-1 capsid that was approved for the treatment of heavily treatment-experienced people with HIV-1 harboring multidrug-resistant virus, and it is used in combination with an optimized background regimen (OBR). Resistance analyses conducted after 2 years of lenacapavir treatment in the phase 2\/3 CAPELLA study are described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CAPELLA enrollment consisted of viremic cases of heavily treatment-experienced people with HIV-1 and resistance to \u22652 drugs per class in at least 3 of the 4 main drug classes. Postbaseline resistance in participants experiencing virologic failure was evaluated by resistance assays (HIV-1 capsid, protease, reverse transcriptase, and integrase genotypic\/phenotypic tests). Adherence to OBR was assessed by plasma drug measurement via liquid chromatography\u2013tandem mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After 2 years, lenacapavir + OBR treatment led to HIV-1 RNA suppression in 82% of participants (missing = excluded). Treatment-emergent capsid resistance occurred in 19% (14\/72) of participants, including capsid mutations M66I, Q67H\/K\/N, K70H\/N\/R\/S, and\/or N74D\/H\/K, which were all associated with functional lenacapavir monotherapy. Seven participants with lenacapavir resistance reattained HIV-1 RNA &amp;lt;50\u2005copies\/mL upon OBR resumption or change while maintaining lenacapavir treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Emergence of lenacapavir resistance after 2 years in CAPELLA was a consequence of functional lenacapavir monotherapy. In half of participants with lenacapavir resistance, continued treatment with lenacapavir + active OBR led to HIV-1 RNA resuppression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf050","type":"journal-article","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T23:20:09Z","timestamp":1737847209000},"page":"1239-1245","source":"Crossref","is-referenced-by-count":40,"title":["Resistance Analyses in Heavily Treatment-Experienced People With HIV Treated With the Novel HIV Capsid Inhibitor Lenacapavir After 2 Years"],"prefix":"10.1093","volume":"231","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0911-4237","authenticated-orcid":false,"given":"Nicolas A","family":"Margot","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamshi","family":"Jogiraju","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc , Foster City, 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