{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:02:15Z","timestamp":1784538135969,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>People with HIV\u20101 may find adhering to life\u2010long daily oral antiretroviral therapy difficult, which can lead to treatment failure or drug resistance. Longer\u2010acting treatments may improve adherence, treatment outcomes, and quality of life. Islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, plus lenacapavir (LEN), the first\u2010in\u2010class HIV\u20101 capsid inhibitor, are being evaluated as a weekly oral regimen for HIV\u20101. We investigated drug\u2013drug interactions (DDI) between ISL and LEN by evaluating the pharmacokinetics and safety of a single\u2010dose oral co\u2010administration of 20 mg of ISL and 600 mg of LEN relative to single\u2010agent administration in 55 adults without HIV. Co\u2010administration showed similar pharmacokinetic profiles compared with single\u2010agent administration; no clinically meaningful pharmacokinetic DDI was identified. The percent geometric least\u2010squares mean (%GLSM) ratios for ISL exposure parameters were 88%\u2013105%, and corresponding 90% confidence intervals (CIs) were within prespecified bounds (60%\u2013167%). While there were no clinically significant differences in LEN exposure between ISL+LEN and LEN administration, the %GLSM ratios for LEN exposures were 80%\u201390%, with 90% CIs within 60%\u2013167% except for maximum LEN concentration. High percentage coefficient of variation was observed for LEN pharmacokinetic parameters, resulting in relatively wide 90% CIs. ISL and LEN were generally well tolerated, with no serious or Grade 3 or 4 adverse events, deaths, or discontinuations of the study due to an adverse event. These results and positive initial findings from an ongoing Phase 2 study (NCT05052996) support further clinical development of ISL and LEN as a weekly combination oral treatment for HIV\u20101.<\/jats:p>","DOI":"10.1002\/jcph.70218","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:49:51Z","timestamp":1780069791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase 1 Study to Evaluate the Potential Drug\u2013Drug Interaction Between Islatravir and Lenacapavir"],"prefix":"10.1002","volume":"66","author":[{"given":"Haeyoung","family":"Zhang","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"West","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  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Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Llamoso","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rhee","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0238-2252","authenticated-orcid":false,"given":"Dhananjay D.","family":"Marathe","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2019.1698946"},{"key":"e_1_2_10_3_1","volume-title":"Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach","author":"World Health Organization"},{"key":"e_1_2_10_4_1","volume-title":"Guidelines for the use of antiretroviral agents in adults and adolescents with HIV","author":"US Department of Health and Human Services"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12981-024-00657-w"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-020-03055-1"},{"key":"e_1_2_10_7_1","volume-title":"Sunlenca highlights of prescribing information","author":"U.S. Food and Drug Administration"},{"key":"e_1_2_10_8_1","volume-title":"Cabenuva highlights of prescribing information","author":"U.S. Food and Drug Administration"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy247"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12030334"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad390"},{"key":"e_1_2_10_12_1","volume-title":"Sunlenca. Summary of product characteristics","author":"European Medicines Agency"},{"key":"e_1_2_10_13_1","volume-title":"Yeztugo. Highlights of prescribing information","author":"U.S. Food and Drug Administration"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13048"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000004142"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.7326\/ANNALS-25-01939"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-014-0212-1"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13081566"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25858"},{"issue":"7","key":"e_1_2_10_20_1","first-page":"601","article-title":"Pharmacokinetic drug\u2010drug interaction and their implication in clinical management","volume":"18","author":"Palleria C","year":"2013","journal-title":"J Res Med Sci"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_10_22_1","unstructured":"ClinicalTrials.gov. NCT04223791: switch to doravirine\/islatravir (DOR\/ISL) in human immunodeficiency virus 1 (HIV\u20101) participants treated with bictegravir\/emtricitabine\/tenofovir alafenamide (BIC\/FTC\/TAF) (MK\u20108591A\u2010018).https:\/\/www.clinicaltrials.gov\/study\/NCT04223791."},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01344-23"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(19)30372-8"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaf222"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(24)00030-4"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(24)00031-6"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaf077"},{"key":"e_1_2_10_29_1","unstructured":"Clinical Trials.gov. NCT06630286: Study to compare an oral weekly islatravir\/lenacapavir regimen with bictegravir\/emtricitabine\/tenofovir alafenamide in virologically suppressed people with HIV\u20101 (ISLEND\u20101).2025. Accessed August 2025.https:\/\/clinicaltrials.gov\/study\/NCT06630286."},{"key":"e_1_2_10_30_1","unstructured":"ClinicalTrials.gov. NCT06630299: Study to compare an oral weekly islatravir\/\u200blenacapavir regimen with standard of care in virologically suppressed people with HIV\u20101 (ISLEND\u20102).2025. 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Paper presented at:2020 Conference on Retroviruses and Opportunistic Infections; Abstract 470; March 8\u201311 2020;Boston Massachusetts."}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70218","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70218","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70218","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:06:20Z","timestamp":1784534780000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/jcph.70218"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70218","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"assertion":[{"value":"2026-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70218"}}