{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:24:37Z","timestamp":1777379077711,"version":"3.51.4"},"reference-count":29,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["AIDS Research and Human Retroviruses"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To assess the antiviral activity, pharmacokinetics, and safety of MK-6186 in HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI)-na\u00efve, HIV-1-infected male participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Double-blind, randomized, two-panel study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In 2 sequential panels, 18 participants received MK-6186 (40 mg [Panel A] or 150 mg [Panel B]) or matching placebo once daily for 7 days. Plasma samples were collected for measurement of HIV-1 RNA levels and MK-6186 pharmacokinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      For the mean change from baseline in HIV-1 RNA (log\n                      <jats:sub>10<\/jats:sub>\n                      copies\/mL) at 24 h post Day 7 dose, the mean difference (90% confidence interval) between MK-6186 and placebo was \u22121.54 (\u22121.73, \u22121.34) in the 40-mg group and \u22121.28 (\u22121.81, \u22120.75) in the 150-mg group. One participant in the 150-mg group had viral rebound at 24 h after Day 6 dosing (Day 7 predose) associated with outgrowth of the V106A minority variant. Ultra-deep sequencing confirmed expansion of this predose minority variant from 0.26% to 63.67%. No outgrowth or rebound was seen in another participant in whom a V106A minority variant was also detected. MK-6186 was generally well tolerated. MK-6186 was rapidly absorbed with peak concentrations at 2 h followed by a biphasic decline. The effective t\u00bd of MK-6186 was 43.9 to 48.7 h. Steady state was not achieved.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Daily monotherapy with MK-6186 demonstrated robust antiviral activity with maximal antiviral activity at a dose of 40 mg. One participant in the 150-mg group exhibited viral rebound with outgrowth of the resistant V106A minority variant, demonstrating a risk of resistance development typical of NNRTIs. The reason for this outgrowth remains unclear as no outgrowth occurred in a participant in the 40-mg group in whom the V106A minority variant was also detected. MK-6186 may be an alternative next-generation NNRTI in combination therapy, in that combination antiretroviral therapy could prevent outgrowth of resistant minority variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/aid.2023.0152","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T07:32:56Z","timestamp":1726644776000},"page":"11-19","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A Randomized, Double-Blind, Placebo-Controlled, Short-Term Monotherapy Study of MK-6186, an HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor, in Treatment-Na\u00efve HIV-Infected Participants"],"prefix":"10.1177","volume":"41","author":[{"given":"Dirk","family":"Sch\u00fcrmann","sequence":"first","affiliation":[{"name":"Charit\u00e9 Research Organisation, Berlin, Germany."},{"name":"Charit\u00e9 - Department of Infectious Diseases, Respiratory Medicine and Critical Care, Universit\u00e4tsmedizin Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"H\u00fcser","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Research Organisation, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frieder","family":"Pf\u00e4fflin","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Department of Infectious Diseases, Respiratory Medicine and Critical Care, Universit\u00e4tsmedizin Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Cilissen","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge","family":"De Lepeleire","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"Larson","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matt S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew L.","family":"Rizk","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Institute of Virology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"D\u00e4umer","sequence":"additional","affiliation":[{"name":"Seq-IT GmbH &amp; Co.KG, Kaiserslautern, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam S.","family":"Stegemann","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Department of Infectious Diseases, Respiratory Medicine and Critical Care, Universit\u00e4tsmedizin Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selwyn A.","family":"Stoch","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Wagner","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Research Organisation, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8334-4815","authenticated-orcid":false,"given":"Marian","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"e_1_3_5_2_2","unstructured":"AIDSMAP. 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