{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:23:28Z","timestamp":1790105008972,"version":"4.0.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck Sharp & Dohme LLC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>MK-8527 is a novel oral nucleoside reverse transcriptase translocation inhibitor under clinical development as HIV-1 (HIV) prevention. Two Phase 1 single-dose monotherapy studies were conducted to evaluate antiretroviral activity, pharmacokinetics (PK), and safety of MK-8527 in adults with HIV who had not previously taken antiretroviral agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In 2 Phase 1 studies, participants received a single oral dose of MK-8527 (0.25, 0.5, 1, 3, or 10 mg). Reduction in viral load (measured as log10 plasma HIV RNA copies\/mL at 7 days post-dose), PK of plasma MK-8527 through 7 days, intracellular MK-8527-triphosphate (TP, the active form of MK-8527) through 28 days, exposure\u2013response relationship, and safety through 28 days were assessed. Adverse events were descriptively summarized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 37 participants completed the studies. After single doses of MK-8527 0.5 to 10 mg, the mean decrease in HIV RNA at 7 days-post dose was \u22651.0 log10 copies\/mL. The inhibitory quotient (defined as the ratio of MK-8527-TP concentration at 168 hours post-dose [C168] to the mean intracellular concentration of MK-8527-TP at the half-maximal inhibitory concentration [IC50]) exceeded 3 at single doses of \u22650.5 mg. MK-8527 at all dose levels was well tolerated, with a limited number of mild or moderate adverse events that were determined by investigators to be unrelated to the study treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In adults with HIV who had not previously taken antiretroviral agents, single doses of MK-8527 as low as 0.5 mg achieved \u22651.0 log10 decreases in HIV RNA at 7 days post-dose administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>www.clinicaltrials.gov NCT03615183, NCT05494736<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag135","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:35:57Z","timestamp":1773329757000},"page":"e984-e991","source":"Crossref","is-referenced-by-count":2,"title":["Antiretroviral Activity, Pharmacokinetics, and Safety of MK-8527, an Oral Nucleoside Reverse Transcriptase Translocation Inhibitor, in Adults With HIV-1 Who Had Not Previously Taken Antiretroviral Agents: Results From 2 Open-Label, Phase 1 Studies"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8083-0412","authenticated-orcid":false,"given":"Russ P","family":"Carstens","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. , 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