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In this study, we examined the potential of gp41 fusion inhibitors (FIs) as candidate anti-HIV microbicides. Preclinical evaluation of four FIs, C34, T20, T1249, and L'644, was performed using cellular and\n            <jats:italic>ex vivo<\/jats:italic>\n            genital and colorectal tissue explant models. Increased and sustained activity was detected for L'644, a cholesterol-derivatized version of C34, relative to the other FIs. The higher potency of L'644 was further increased with sustained exposure of cells or tissue to the compound. The activity of L'644 was not affected by biological fluids, and the compound was still active when tissue explants were treated after viral exposure. L'644 was also more active than other FIs against a viral escape mutant resistant to reverse transcriptase inhibitors (RTIs), demonstrating the potential of L'644 to be included as part of a multiactive antiretroviral (ARV) combination-based microbicide. These data support the further development of L'644 for microbicide application.\n          <\/jats:p>","DOI":"10.1128\/aac.06108-11","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T04:11:22Z","timestamp":1329192682000},"page":"2347-2356","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Preclinical Evaluation of the HIV-1 Fusion Inhibitor L'644 as a Potential Candidate Microbicide"],"prefix":"10.1128","volume":"56","author":[{"given":"Sarah","family":"Harman","sequence":"first","affiliation":[{"name":"Centre for Infection, Division of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Herrera","sequence":"additional","affiliation":[{"name":"Centre for Infection, Division of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Armanasco","sequence":"additional","affiliation":[{"name":"Centre for Infection, Division of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Nuttall","sequence":"additional","affiliation":[{"name":"International Partnership for Microbicides, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Shattock","sequence":"additional","affiliation":[{"name":"Centre for Infection, Division of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200008180-00011"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.684"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.90.3.732"},{"key":"e_1_3_2_5_2","first-page":"S133","article-title":"Prevalence of mutations associated with antiretroviral drug resistance among men and women newly diagnosed with HIV in 10 US cities, 1997\u20132001","volume":"8","author":"Bennett DE","year":"2003","unstructured":"BennettDE. 2003. 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