{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:53:46Z","timestamp":1780793626942,"version":"3.54.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>MK-8527 is a novel nucleoside reverse transcriptase translocation inhibitor being evaluated for prevention of HIV-1 acquisition. MK-8527 is phosphorylated intracellularly to its active form, MK-8527-triphosphate, which inhibits HIV-1 replication. This study evaluated the efficacy of oral MK-8527 as pre-exposure prophylaxis in rhesus macaques challenged intrarectally with simian\u2013human immunodeficiency virus (SHIV).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two groups of male macaques (n = 8 per group) received weekly oral doses of MK-8527 for 12 weeks. Starting 1 week after treatment initiation, the macaques received weekly intrarectal challenge with SHIV162P3 for 10 weeks. Each group was treated in 3 dosing panels: Group 1 received MK-8527 6, 1, and 0\u2005mg\/kg (vehicle only), whereas Group 2 received MK-8527 2, 0.3, and 0.1\u2005mg\/kg. A washout period of \u22654 weeks followed each dosing panel. A control group (n = 8) was challenged without receiving MK-8527. Plasma viral loads were monitored weekly, with infection confirmed by 2 consecutive measurements of SHIV RNA &amp;gt;100\u2005copies\/mL. Concentrations of MK-8527 phosphorylated forms were quantified using liquid chromatography-tandem mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Once-weekly doses of MK-8527 \u2265 0.1\u2005mg\/kg for 12 weeks conferred complete protection against intrarectal SHIV acquisition, and 7\/8 untreated control macaques and 5\/8 vehicle-only macaques became infected. The rate of infection for macaques receiving MK-8527 was at least 11.1-fold (P = .009) lower compared with the control or vehicle group. MK-8527-triphosphate trough concentrations at 0.1\u2005mg\/kg resulted in a mean inhibitory quotient of 2.2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prophylaxis with MK-8527 completely protected macaques from SHIV infection, supporting its further clinical development for prevention of HIV-1 acquisition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf610","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T12:53:54Z","timestamp":1765630434000},"page":"e923-e931","source":"Crossref","is-referenced-by-count":1,"title":["Weekly Oral Prophylaxis With MK-8527 Protects Rhesus Macaques From Intrarectal Challenge With Simian\u2013Human Immunodeficiency Virus"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4672-8641","authenticated-orcid":false,"given":"Tracy L","family":"Diamond","sequence":"first","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-4115","authenticated-orcid":false,"given":"Yash","family":"Kapoor","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangbiao","family":"Li","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang-Lin","family":"Wan","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A","family":"Boddicker","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill W","family":"Maxwell","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Ngo","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A","family":"Fontenot","sequence":"additional","affiliation":[{"name":"New Iberia Research Center , University of Louisiana at Lafayette, New Iberia, Louisiana ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A","family":"Soileau","sequence":"additional","affiliation":[{"name":"New Iberia Research Center , University of Louisiana at Lafayette, New Iberia, Louisiana ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-2008","authenticated-orcid":false,"given":"Francois J","family":"Villinger","sequence":"additional","affiliation":[{"name":"New Iberia Research Center , University of Louisiana at Lafayette, New Iberia, Louisiana ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay A","family":"Grobler","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubing","family":"Wang","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry L","family":"Fillgrove","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry S","family":"Lange","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Asante-Appiah","sequence":"additional","affiliation":[{"name":"MRL, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"2026042913515686200_jiaf610-B1","author":"UNAIDS"},{"key":"2026042913515686200_jiaf610-B2","doi-asserted-by":"crossref","first-page":"e167818","DOI":"10.1172\/JCI167818","article-title":"Long-acting lenacapavir acts as an effective preexposure prophylaxis in a rectal SHIV challenge macaque model","volume":"133","author":"Bekerman","year":"2023","journal-title":"J Clin Invest"},{"key":"2026042913515686200_jiaf610-B3","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/jama.2023.9865","article-title":"Preexposure prophylaxis for the prevention of HIV: updated evidence report and systematic review for the US preventive services task force","volume":"330","author":"Chou","year":"2023","journal-title":"JAMA"},{"key":"2026042913515686200_jiaf610-B4","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3390\/pharmaceutics16030384","article-title":"Weekly oral tenofovir alafenamide protects macaques from vaginal and rectal simian HIV infection","volume":"16","author":"Massud","year":"2024","journal-title":"Pharmaceutics"},{"key":"2026042913515686200_jiaf610-B5","author":"World Health Organization"},{"key":"2026042913515686200_jiaf610-B6","volume-title":"Prescribing information","author":"YEZTUGO","year":"2025"},{"key":"2026042913515686200_jiaf610-B7","doi-asserted-by":"crossref","first-page":"e048478","DOI":"10.1136\/bmjopen-2020-048478","article-title":"Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations","volume":"12","author":"O Murchu","year":"2022","journal-title":"BMJ Open"},{"key":"2026042913515686200_jiaf610-B8","author":"Centers for Disease Control and Prevention"},{"key":"2026042913515686200_jiaf610-B9","author":"Centers for Disease Control and Prevention"},{"key":"2026042913515686200_jiaf610-B10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa1402269","article-title":"Tenofovir-based preexposure prophylaxis for HIV infection among African women","volume":"372","author":"Marrazzo","year":"2015","journal-title":"N Engl J Med"},{"key":"2026042913515686200_jiaf610-B11","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1016\/S2352-3018(22)00030-3","article-title":"Discontinuation, suboptimal adherence, and reinitiation of oral HIV pre-exposure prophylaxis: a global systematic review and meta-analysis","volume":"9","author":"Zhang","year":"2022","journal-title":"Lancet HIV"},{"key":"2026042913515686200_jiaf610-B12","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1007\/s10461-022-03624-6","article-title":"Perceptions and practicalities influencing pre-exposure prophylaxis adherence among men who have sex with men in England","volume":"26","author":"Arnold-Forster","year":"2022","journal-title":"AIDS Behav"},{"key":"2026042913515686200_jiaf610-B13","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1056\/NEJMoa2101016","article-title":"Cabotegravir for HIV prevention in cisgender men and transgender women","volume":"385","author":"Landovitz","year":"2021","journal-title":"N Engl J Med"},{"key":"2026042913515686200_jiaf610-B14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1001\/jama.2022.22246","article-title":"Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2022 recommendations of the International Antiviral Society-USA panel","volume":"329","author":"Gandhi","year":"2023","journal-title":"JAMA"},{"key":"2026042913515686200_jiaf610-B15","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJMoa2411858","article-title":"Twice-yearly lenacapavir for HIV prevention in men and gender-diverse persons","volume":"392","author":"Kelley","year":"2025","journal-title":"N Engl J Med"},{"key":"2026042913515686200_jiaf610-B16","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1056\/NEJMoa2407001","article-title":"Twice-yearly lenacapavir or daily F\/TAF for HIV prevention in cisgender women","volume":"391","author":"Bekker","year":"2024","journal-title":"N Engl J Med"},{"key":"2026042913515686200_jiaf610-B17","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1007\/s10461-023-04093-1","article-title":"The future of pre-exposure prophylaxis (PrEP) for HIV prevention: a global qualitative consultation on provider perspectives on new products and differentiated service delivery","volume":"27","author":"Henderson","year":"2023","journal-title":"AIDS Behav"},{"key":"2026042913515686200_jiaf610-B18","author":"World Health Organization"},{"key":"2026042913515686200_jiaf610-B19","author":"ClinicalTrials.gov. NCT07071623"},{"key":"2026042913515686200_jiaf610-B20","author":"ClinicalTrials.gov. NCT07044297"},{"key":"2026042913515686200_jiaf610-B21","author":"Carstens"},{"key":"2026042913515686200_jiaf610-B22","doi-asserted-by":"crossref","first-page":"e3003308","DOI":"10.1371\/journal.pbio.3003308","article-title":"MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase translocation with potential for extended-duration dosing","volume":"23","author":"Raheem","year":"2025","journal-title":"PLoS Biol"},{"key":"2026042913515686200_jiaf610-B23","author":"Mayer"},{"key":"2026042913515686200_jiaf610-B24","doi-asserted-by":"crossref","first-page":"e70331","DOI":"10.1111\/cts.70331","article-title":"Safety and pharmacokinetics of MK-8527 in adults without HIV","volume":"18","author":"Gillespie","year":"2025","journal-title":"Clin Transl Sci"},{"key":"2026042913515686200_jiaf610-B25","first-page":"255","article-title":"Nonhuman primate models in AIDS research","volume":"8","author":"Evans","year":"2013","journal-title":"Curr Opin HIV AIDS"},{"key":"2026042913515686200_jiaf610-B26","doi-asserted-by":"crossref","first-page":"e790","DOI":"10.1016\/S2352-3018(23)00256-4","article-title":"HIV pre-exposure prophylaxis and its implementation in the PrEP impact trial in England: a pragmatic health technology assessment","volume":"10","author":"Sullivan","year":"2023","journal-title":"Lancet HIV"},{"key":"2026042913515686200_jiaf610-B27","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1093\/jac\/dku162","article-title":"Tenofovir diphosphate concentrations and prophylactic effect in a macaque model of rectal simian HIV transmission","volume":"69","author":"Anderson","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2026042913515686200_jiaf610-B28","doi-asserted-by":"crossref","first-page":"151ra25","DOI":"10.1126\/scitranslmed.3004006","article-title":"Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men","volume":"4","author":"Anderson","year":"2012","journal-title":"Sci Transl Med"},{"key":"2026042913515686200_jiaf610-B29","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/bcp.14980","article-title":"Multicompartmental pharmacokinetic evaluation of long-acting cabotegravir in healthy adults for HIV preexposure prophylaxis","volume":"88","author":"Shaik","year":"2022","journal-title":"Br J Clin Pharmacol"},{"key":"2026042913515686200_jiaf610-B30","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1177\/10600280221102532","article-title":"Cabotegravir: the first long-acting injectable for HIV preexposure prophylaxis","volume":"57","author":"Durham","year":"2023","journal-title":"Ann Pharmacother"},{"key":"2026042913515686200_jiaf610-B31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/COH.0000000000000219","article-title":"The promise and pitfalls of long-acting injectable agents for HIV prevention","volume":"11","author":"Landovitz","year":"2016","journal-title":"Curr Opin HIV AIDS"},{"key":"2026042913515686200_jiaf610-B32","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1186\/s12879-018-3463-4","article-title":"A systematic review of adherence to oral pre-exposure prophylaxis for HIV\u2014how can we improve uptake and adherence?","volume":"18","author":"Sidebottom","year":"2018","journal-title":"BMC Infect Dis"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf610\/65924867\/jiaf610.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/4\/e923\/65924867\/jiaf610.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/4\/e923\/65924867\/jiaf610.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:52:08Z","timestamp":1777485128000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/233\/4\/e923\/8381540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,12,16]]},"published-print":{"date-parts":[[2026,4,29]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf610","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4,15]]},"published":{"date-parts":[[2025,12,16]]}}}