{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:45:42Z","timestamp":1791413142394,"version":"4.3.3"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"30","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,7,29]]},"abstract":"<jats:p>\n                    We have assessed the potential of the fusion inhibitory peptide T-1249 for development as a vaginal microbicide to prevent HIV-1 sexual transmission. When formulated as a simple gel, T-1249 provided dose-dependent protection to macaques against high-dose challenge with three different SHIVs that used either CCR5 or CXCR4 for infection (the R5 virus SHIV-162P3, the X4 virus SHIV-KU1 and the R5X4 virus SHIV-89.6P), and it also protected against SIVmac251 (R5). Protection of half of the test animals was estimated by interpolation to occur at T-1249 concentrations of \u224840\u2013130 \u03bcM, whereas complete protection was observed at 0.1\u20132 mM.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , T-1249 had substantial breadth of activity against HIV-1 strains from multiple genetic subtypes and in a coreceptor-independent manner. Thus, at 1 \u03bcM in a peripheral blood mononuclear cell-based replication assay, T-1249 inhibited all 29 R5 viruses, all 12 X4 viruses and all 7 R5X4 viruses in the test panel, irrespective of their genetic subtype. Combining lower concentrations of T-1249 with other entry inhibitors (CMPD-167, BMS-C, or AMD3465) increased the proportion of test viruses that could be blocked. In the PhenoSense assay, T-1249 was active against 636 different HIV-1 Env-pseudotyped viruses of varying tropism and derived from clinical samples, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values typically clustered in a 10-fold range \u224810 nM. Overall, these results support the concept of using T-1249 as a component of an entry inhibitor-based combination microbicide to prevent the sexual transmission of diverse HIV-1 variants.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0802666105","type":"journal-article","created":{"date-parts":[[2008,7,22]],"date-time":"2008-07-22T20:44:14Z","timestamp":1216759454000},"page":"10531-10536","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["Tropism-independent protection of macaques against vaginal transmission of three SHIVs by the HIV-1 fusion inhibitor T-1249"],"prefix":"10.1073","volume":"105","author":[{"given":"Ronald S.","family":"Veazey","sequence":"first","affiliation":[{"name":"*Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Ketas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10075; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Johan","family":"Klasse","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10075; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna K.","family":"Davison","sequence":"additional","affiliation":[{"name":"Trimeris, Inc., 3500 Paramount Parkway, Morrisville, NC 27560"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Singletary","sequence":"additional","affiliation":[{"name":"*Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda C.","family":"Green","sequence":"additional","affiliation":[{"name":"*Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Trimeris, Inc., 3500 Paramount Parkway, Morrisville, NC 27560"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10075; 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