{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:57:09Z","timestamp":1753869429329,"version":"3.41.2"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc."],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with robust antiretroviral activity. The efficacy of ISL administered for post\u2010exposure prophylaxis (PEP) was evaluated in a simian immunodeficiency virus (SIV) rhesus macaque intravenous (IV) challenge model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twelve rhesus macaques were challenged with SIVmac251 via IV administration. After 24 hours, six animals received ISL 3.9\u00a0mg\/kg (the minimum effective dose that gives maximal protection) and six animals were untreated controls. In stage 1, treated animals received 4 weekly oral doses of ISL and were monitored for SIV infection for 7 weeks after the last dose. In stage 2, uninfected, treated animals from stage 1 were challenged similarly; 24 hours after challenge, 3 weekly oral doses of ISL 3.9 mg\/kg were initiated. The treated animals were monitored for 7 weeks, as in stage 1. Uninfected, treated animals (from stage 2) entered stage 3. In stage 3, the animals were challenged as in stage 2; 24 hours after challenge, 2 weekly oral doses of ISL 3.9 mg\/kg were initiated. The treated animals were monitored for 7 weeks, as before. Finally, in stage 4, uninfected, treated animals were challenged using IV administration and 24 hours later were treated with a single oral dose of ISL 3.9 mg\/kg and monitored for 7 weeks. Infection was monitored through plasma viral RNA and proviral DNA amplification. Virus\u2010specific antibody responses were measured using a commercial assay. ISL concentrations in plasma and ISL triphosphate (ISL\u2010TP) levels in peripheral blood mononuclear cells were measured longitudinally.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All untreated controls were viraemic 7 days after SIVmac251 IV challenge. All six ISL\u2010treated animals were completely protected in stages 1\u20133 (Fisher exact test <jats:italic>p<\/jats:italic> = 0.0022). In stage 4, two of six ISL\u2010treated animals became infected with wild\u2010type SIVmac251: viraemia was observed at days 14 and 49 in the two animals (Fisher exact test <jats:italic>p<\/jats:italic> = 0.06). Both animals had unquantifiable ISL\u2010TP on the day viraemia was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Two weekly oral doses of ISL 3.9 mg\/kg, administered 24 hours post IV SIV exposure, prevents infection of rhesus macaques. These results support further investigation of a long\u2010acting oral NRTTI for PEP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.26507","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T05:40:04Z","timestamp":1750311604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness of islatravir post\u2010exposure prophylaxis after intravenous challenge with simian immunodeficiency virus in rhesus macaques"],"prefix":"10.1002","volume":"28","author":[{"given":"Martin","family":"Markowitz","sequence":"first","affiliation":[{"name":"Aaron Diamond AIDS Research Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agegnehu","family":"Gettie","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"St. Bernard","sequence":"additional","affiliation":[{"name":"Aaron Diamond AIDS Research Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooke","family":"Grasperge","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center  Covington Louisiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Vargo","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Pham","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"Fillgrove","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal","family":"Dube","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4672-8641","authenticated-orcid":false,"given":"Tracy L.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria J.","family":"Hazuda","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay A.","family":"Grobler","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00270-09"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102894"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa476"},{"volume-title":"Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV\u2010United States","year":"2016","author":"CDC","key":"e_1_2_11_5_1"},{"volume-title":"Guidelines for HIV post\u2010exposure prophylaxis","year":"2024","author":"WHO","key":"e_1_2_11_6_1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.24543"},{"issue":"1","key":"e_1_2_11_8_1","first-page":"40","article-title":"The sugar ring conformation of 4'\u2010ethynyl\u20102\u2010fluoro\u20102'\u2010deoxyadenosine and its recognition by the polymerase active site of HIV reverse transcriptase","volume":"57","author":"Kirby KA","year":"2011","journal-title":"Cell Mol Biol"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.562694"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.036616"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.03.001"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00133-22"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.04.007"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx280"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2697"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2018.07.014"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002755"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(19)30372-8"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00744-17"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00723-12"},{"key":"e_1_2_11_21_1","unstructured":"GroblerJ LaiM\u2010T BarrettSE GindyM FillgroveKL AnkromW et\u00a0al.Long\u2010acting oral and parenteral dosing of MK\u20108591 for HIV treatment or prophylaxis.Conference on Retroviruses and Opportunistic Infections (CROI) 22\u201325 February2016 Boston MA."},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz271"},{"key":"e_1_2_11_23_1","unstructured":"ClinicalTrials.gov.NCT05630755: a switch to doravirine\/islatravir (DOR\/ISL) in participants with human immunodeficiency virus type 1 (HIV\u20101) who are virologically suppressed on bictegravir\/emtricitabine\/tenofovir alafenamide (BIC\/FTC\/TAF) (MK\u20108591A\u2010052). 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