{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:06:24Z","timestamp":1779149184123,"version":"3.51.4"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"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":[[2012,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>HIV continues to be a problem worldwide. Topical vaginal microbicides represent one option being evaluated to stop the spread of HIV. With drug candidates that have a specific action against HIV now being studied, it is important that, when appropriate and based on the mechanism of action, the drug permeates the tissue so that it can be delivered to specific targets which reside there. Novel formulations of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) and the nonnucleoside reverse transcriptase inhibitor UC781 have been developed and evaluated here. Gels with three distinct rheological properties were prepared. The three gels released both UC781 and TFV under<jats:italic>in vitro<\/jats:italic>conditions at concentrations equal to or above the reported 50% effective concentrations (EC<jats:sub>50<\/jats:sub>s). The drug concentrations in ectocervical tissues were well in excess of the reported EC<jats:sub>50<\/jats:sub>s. The gels maintain ectocervical viability and prevent infection of ectocervical explants after a HIV-1 challenge. This study successfully demonstrates the feasibility of using this novel combination of antiretroviral agents in an aqueous gel as an HIV infection preventative.<\/jats:p>","DOI":"10.1128\/aac.06284-11","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T03:32:13Z","timestamp":1332214333000},"page":"3058-3066","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Characterization of UC781-Tenofovir Combination Gel Products for HIV-1 Infection Prevention in an<i>Ex Vivo<\/i>Ectocervical Model"],"prefix":"10.1128","volume":"56","author":[{"given":"Marilyn","family":"Cost","sequence":"first","affiliation":[{"name":"Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlene S.","family":"Dezzutti","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith R.","family":"Clark","sequence":"additional","affiliation":[{"name":"CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Friend","sequence":"additional","affiliation":[{"name":"CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman","family":"Akil","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa Cencia","family":"Rohan","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193748"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1097\/QAD.0b013e32834541d9","article-title":"Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women","volume":"25","author":"Abdool Karim SS","year":"2011","unstructured":"Abdool KarimSS. 2011. Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS 25:957\u2013966.","journal-title":"AIDS"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1086\/462424","article-title":"A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection","volume":"192","author":"Abner SR","year":"2005","unstructured":"AbnerSR. 2005. A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection. J. Infect. Dis. 192:1545\u20131556.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s13346-011-0022-6","article-title":"Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission","volume":"1","author":"Akil A","year":"2011","unstructured":"AkilA. 2011. Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission. Drug Deliv. Transl. Res. 1:209\u2013222.","journal-title":"Drug Deliv. Transl. Res."},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S0026-895X(25)09254-5","article-title":"Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication","volume":"50","author":"Balzarini J","year":"1996","unstructured":"BalzariniJ. 1996. Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication. Mol. Pharmacol. 50:394\u2013401.","journal-title":"Mol. Pharmacol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199810000-00004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970140u"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF03190381","article-title":"Chemical enhancers for transdermal drug transport","volume":"26","author":"Bauerov\u00e1 K","year":"2001","unstructured":"Bauerov\u00e1K MatusovaD KassaiZ. 2001. Chemical enhancers for transdermal drug transport. Eur. J. Drug Metab. Pharmacokinet. 26:85\u201394.","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1089\/088922202760072339","article-title":"Attenuated infectivity of HIV type 1 from epithelial cells pretreated with a tight-binding nonnucleoside reverse transcriptase inhibitor","volume":"18","author":"Borkow G","year":"2002","unstructured":"BorkowG SalomonH WainbergMA ParniakMA. 2002. Attenuated infectivity of HIV type 1 from epithelial cells pretreated with a tight-binding nonnucleoside reverse transcriptase inhibitor. AIDS Res. Hum. Retroviruses 18:711\u2013714.","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1080\/09540120701294237","article-title":"Acceptability of tenofovir gel as a vaginal microbicide by US male participants in a phase I clinical trial (HPTN 050)","volume":"19","author":"Carballo-Di\u00e9guez A","year":"2007","unstructured":"Carballo-Di\u00e9guezA. 2007. Acceptability of tenofovir gel as a vaginal microbicide by US male participants in a phase I clinical trial (HPTN 050). AIDS Care 19:1026\u20131031.","journal-title":"AIDS Care"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"e157","DOI":"10.1371\/journal.pmed.0050157","article-title":"Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel","volume":"5","author":"Cranage M","year":"2008","unstructured":"CranageM. 2008. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med. 5:e157.","journal-title":"PLoS Med."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01129-06"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.fertnstert.2007.01.131","article-title":"Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent genital transmission of HIV-1","volume":"88","author":"D'Cruz OJ","year":"2007","unstructured":"D'CruzOJ UckunFM. 2007. Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent genital transmission of HIV-1. Fertil. Steril. 88(4 Suppl.):1197\u20131206.","journal-title":"Fertil. Steril."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.10.3834-3844.2004"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001474"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.olq.0000223287.46097.4b"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11179-11186.2005"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01156-08"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/095632020901900401","article-title":"The future of HIV microbicides: challenges and opportunities","volume":"19","author":"Garg AB","year":"2009","unstructured":"GargAB NuttallJ RomanoJ. 2009. The future of HIV microbicides: challenges and opportunities. Antivir. Chem. Chemother. 19:143\u2013150.","journal-title":"Antivir. Chem. Chemother."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.qai.0000159671.25950.74","article-title":"In vitro and in vivo: the story of nonoxynol 9","volume":"39","author":"Hillier SL","year":"2005","unstructured":"HillierSL. 2005. In vitro and in vivo: the story of nonoxynol 9. J. Acquir. Immune Defic. Syndr. 39:1\u20138.","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.9.4440-4446.2006"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ejps.2009.11.007","article-title":"Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir","volume":"39","author":"Johnson TJ","year":"2010","unstructured":"JohnsonTJ GuptaKM FabianJ AlbrightTH KiserPF. 2010. Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. Eur. J. Pharm. Sci. 39:203\u2013212.","journal-title":"Eur. J. Pharm. Sci."},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/jps.20774","article-title":"Interpreting properties of microbicide drug delivery gels: analyzing deployment kinetics due to squeezing","volume":"96","author":"Kieweg SL","year":"2007","unstructured":"KiewegSL KatzDF. 2007. Interpreting properties of microbicide drug delivery gels: analyzing deployment kinetics due to squeezing. J. Pharm. Sci. 96:835\u2013850.","journal-title":"J. Pharm. Sci."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23089"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.5.1830-1836.2005"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-010-0244-1"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000210608.70762.c3"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1851-1856.2002"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.virol.2009.01.002","article-title":"Characterization of vaginal transmission of a simian human immunodeficiency virus (SHIV) encoding the reverse transcriptase gene from HIV-1 in Chinese rhesus macaques","volume":"386","author":"Pal R","year":"2009","unstructured":"PalR. 2009. Characterization of vaginal transmission of a simian human immunodeficiency virus (SHIV) encoding the reverse transcriptase gene from HIV-1 in Chinese rhesus macaques. Virology 386:102\u2013108.","journal-title":"Virology"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01073-09"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00984-06"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2478\/v10007-011-0025-3","article-title":"Design and evaluation of a bioadhesive film for transdermal delivery of propranolol hydrochloride","volume":"61","author":"Rasool BK","year":"2011","unstructured":"RasoolBK AzizUS SarheedO RasoolAA. 2011. Design and evaluation of a bioadhesive film for transdermal delivery of propranolol hydrochloride. Acta Pharm. 61:271\u2013282.","journal-title":"Acta Pharm."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009310"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61842-5"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707957"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1208\/s12248-008-9070-3","article-title":"Characterization of cyclodextrin inclusion complexes of the anti-HIV non-nucleoside reverse transcriptase inhibitor UC781","volume":"10","author":"Yang H","year":"2008","unstructured":"YangH ParniakMA IsaacsCE HillierSL RohanLC. 2008. Characterization of cyclodextrin inclusion complexes of the anti-HIV non-nucleoside reverse transcriptase inhibitor UC781. AAPS J. 10:606\u2013613.","journal-title":"AAPS J."},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1097\/00002030-200303280-00002","article-title":"Blocking of cell-free and cell-associated HIV-1 transmission through human cervix organ culture with UC781","volume":"17","author":"Zussman A","year":"2003","unstructured":"ZussmanA LaraL LaraHH BentwichZ BorkowG. 2003. Blocking of cell-free and cell-associated HIV-1 transmission through human cervix organ culture with UC781. AIDS 17:653\u2013661.","journal-title":"AIDS"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.06284-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.06284-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T15:44:45Z","timestamp":1742744685000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.06284-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,6]]}},"alternative-id":["10.1128\/AAC.06284-11"],"URL":"https:\/\/doi.org\/10.1128\/aac.06284-11","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6]]},"assertion":[{"value":"2011-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-03-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-05-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}