{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T17:11:22Z","timestamp":1770484282004,"version":"3.49.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"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":[[2011,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            TMC310911 is a novel human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) structurally closely related to darunavir (DRV) but with improved virological characteristics. TMC310911 has potent activity against wild-type (WT) HIV-1 (median 50% effective concentration [EC\n            <jats:sub>50<\/jats:sub>\n            ], 14 nM) and a wide spectrum of recombinant HIV-1 clinical isolates, including multiple-PI-resistant strains with decreased susceptibility to currently approved PIs (fold change [FC] in EC\n            <jats:sub>50<\/jats:sub>\n            , &gt;10). For a panel of 2,011 recombinant clinical isolates with decreased susceptibility to at least one of the currently approved PIs, the FC in TMC310911 EC\n            <jats:sub>50<\/jats:sub>\n            was \u22644 for 82% of isolates and \u226410 for 96% of isolates. The FC in TMC310911 EC\n            <jats:sub>50<\/jats:sub>\n            was \u22644 and \u226410 for 72% and 94% of isolates with decreased susceptibility to DRV, respectively.\n            <jats:italic>In vitro<\/jats:italic>\n            resistance selection (IVRS) experiments with WT virus and TMC310911 selected for mutations R41G or R41E, but selection of resistant virus required a longer time than IVRS performed with WT virus and DRV. IVRS performed with r13025, a multiple-PI-resistant recombinant clinical isolate, and TMC310911 selected for mutations L10F, I47V, and L90M (FC in TMC310911 EC\n            <jats:sub>50<\/jats:sub>\n            = 16). IVRS performed with r13025 in the presence of DRV required less time and resulted in more PI resistance-associated mutations (V32I, I50V, G73S, L76V, and V82I; FC in DRV EC\n            <jats:sub>50<\/jats:sub>\n            = 258). The activity against a comprehensive panel of PI-resistant mutants and the limited\n            <jats:italic>in vitro<\/jats:italic>\n            selection of resistant viruses under drug pressure suggest that TMC310911 represents a potential drug candidate for the management of HIV-1 infection for a broad range of patients, including those with multiple PI resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.00748-11","type":"journal-article","created":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T03:46:33Z","timestamp":1315367193000},"page":"5723-5731","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["TMC310911, a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor, Shows\n            <i>In Vitro<\/i>\n            an Improved Resistance Profile and Higher Genetic Barrier to Resistance Compared with Current Protease Inhibitors"],"prefix":"10.1128","volume":"55","author":[{"given":"Inge","family":"Dierynck","sequence":"first","affiliation":[{"name":"Tibotec BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herwig","family":"Van Marck","sequence":"additional","affiliation":[{"name":"Tibotec BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia","family":"Van Ginderen","sequence":"additional","affiliation":[{"name":"Tibotec BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim H. 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