{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:21:48Z","timestamp":1753881708398,"version":"3.41.2"},"reference-count":15,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,8,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia\u2019s QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (\u0394\u0394QTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was &lt;10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a \u0394\u0394QTcP &gt;10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00464-24","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T10:22:47Z","timestamp":1719915767000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Thorough QT\/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8403-267X","authenticated-orcid":true,"given":"Randolph P.","family":"Matthews","sequence":"first","affiliation":[{"name":"Translational Medicine, Biostatistics and Research Decision Sciences, Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Medicine, Biostatistics and Research Decision Sciences, Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Matthews","sequence":"additional","affiliation":[{"name":"Translational Medicine, Biostatistics and Research Decision Sciences, Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin L.","family":"Butterfield","sequence":"additional","affiliation":[{"name":"Translational Medicine, Biostatistics and Research Decision Sciences, Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"Clinical Research, Celerion, Tempe, Arizona, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"Translational Medicine, Biostatistics and Research Decision Sciences, Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Translational Medicine, Biostatistics and Research Decision Sciences, Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"UNAIDS. 2023 fact sheet - global HIV statistics. Available from: https:\/\/www.unaids.org\/en\/resources\/fact-sheet. Retrieved 24 Oct 2023."},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61809-7"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00133-22"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.562694"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605223113"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(19)30372-8"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13048"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002755"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00931-22"},{"key":"e_1_3_5_11_2","unstructured":"Squires K Correll TA Robertson MN Klopfer SO Hwang PMT Zhou Y-P Martin E Rhee E. Effect of islatravir on total lymphocyte and lymphocyte subset counts.Presented at the CROI: Conference on Retroviruses and Opportunistic Infections Seattle WA USA. Accessed 24 October 2023. https:\/\/www.croiconference.org\/abstract\/effect-of-islatravir-on-total-lymphocyte-and-lymphocyte-subset-counts."},{"key":"e_1_3_5_12_2","unstructured":"ICH. 2005. The clinical evaluation of QT\/QTs interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs: step 5. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-e-14-clinical-evaluation-qt\/qts-interval-prolongation-proarrhythmic-potential-non-antiarrhythmic-drugs-step-5_en.pdf. Retrieved 24 Oct 2023."},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.33"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-017-0552-x"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010381498"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2018-0101"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00464-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00464-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T13:03:42Z","timestamp":1723035822000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00464-24"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,7]]},"references-count":15,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8,7]]}},"alternative-id":["10.1128\/aac.00464-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.00464-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"type":"print","value":"0066-4804"},{"type":"electronic","value":"1098-6596"}],"subject":[],"published":{"date-parts":[[2024,8,7]]},"assertion":[{"value":"2024-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00464-24"}}