{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:19Z","timestamp":1787008999331,"version":"build-2736575974"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lenacapavir (LEN) is an HIV-1 capsid inhibitor being evaluated for pre-exposure prophylaxis (PrEP). The PURPOSE trials assessed the efficacy of LEN and emtricitabine\/tenofovir disoproxil fumarate (F\/TDF) in cisgender women (PURPOSE 1; P1) and in cisgender men, transgender women, transgender men and gender non-binary persons (PURPOSE 2; P2). Emtricitabine\/tenofovir alafenamide (F\/TAF) was also assessed in P1. Both studies demonstrated the superiority of LEN to F\/TDF. We describe resistance analyses from P1 and P2, which provide the first data regarding emergent drug resistance in the context of LEN for PrEP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HIV testing was performed at screening, baseline, and every study visit. Participants who acquired HIV-1 with a viral load of \u2265200 copies\/mL were evaluated for resistance by genotyping of the HIV-1 capsid, protease, reverse transcriptase and integrase genes at HIV diagnosis. Adherence in the F\/TDF and F\/TAF groups was measured by dried blood spot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Resistance to LEN was detected in 0 of 2134 participants (P1) and 2 of 2179 participants (P2); both developed N74D. Four participants in each study receiving LEN were found to have unrecognized HIV-1 at baseline; 4\/8 participants developed N74D. In P1, 2\/37 participants analyzed for resistance in the F\/TAF group had M184I \u00b1 K65R. In the F\/TDF groups, M184M\/I\/V was detected in 1\/16 participants (P1) and 1\/9 participants (P2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Acquisition of HIV while receiving LEN and resistance to LEN in the context of unrecognized HIV was rare but associated with the emergence of the N74D LEN resistance-associated substitution in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf533","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T11:47:25Z","timestamp":1760788045000},"page":"e203-e211","source":"Crossref","is-referenced-by-count":2,"title":["Resistance Analyses of Lenacapavir, Emtricitabine\/Tenofovir Alafenamide and Emtricitabine\/Tenofovir Disoproxil Fumarate in the PURPOSE 1 and 2 Studies"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4206-2216","authenticated-orcid":false,"given":"Stephanie","family":"Cox","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc. , Foster City, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7201-533X","authenticated-orcid":false,"given":"Kristen","family":"Andreatta","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. , Foster City, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-4560","authenticated-orcid":false,"given":"Matthew R","family":"Hendricks","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. , Foster City, California 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