{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T10:54:38Z","timestamp":1782644078320,"version":"3.54.5"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"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":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV\/glycerol\/water semisolid paste and then end-sealed to create IVRs.\n            <jats:italic>In vitro<\/jats:italic>\n            , TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg\/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day\n            <jats:italic>in vivo<\/jats:italic>\n            sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 10\n            <jats:sup>4<\/jats:sup>\n            ng\/g, 10\n            <jats:sup>6<\/jats:sup>\n            ng\/g, and 10\n            <jats:sup>1<\/jats:sup>\n            ng\/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to na\u00efve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic.\n          <\/jats:p>","DOI":"10.1128\/aac.01431-12","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T03:19:13Z","timestamp":1348543153000},"page":"6272-6283","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":84,"title":["A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis"],"prefix":"10.1128","volume":"56","author":[{"given":"Todd J.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith R.","family":"Clark","sequence":"additional","affiliation":[{"name":"CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School (EVMS), Arlington, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore H.","family":"Albright","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Nebeker","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"Tuitupou","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin T.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Fabian","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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