{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:00:37Z","timestamp":1779184837471,"version":"3.51.4"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19 AI113127"],"award-info":[{"award-number":["U19 AI113127"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["P51OD11132"],"award-info":[{"award-number":["P51OD11132"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Oral preexposure prophylaxis (PrEP) has been approved for prophylaxis of HIV-1 transmission but is associated with high costs and issues of adherence. Protection from anal transmission of HIV using topical microbicides and methods congruent with sexual behavior offers the promise of improved adherence. We compared the pharmacokinetics (PK) and\n            <jats:italic>ex vivo<\/jats:italic>\n            efficacy of iso-osmolar (IOsm) and hypo-osmolar (HOsm) rectal enema formulations of tenofovir (TFV) in rhesus macaques. Single-dose PK of IOsm or HOsm high-dose (5.28 mg\/ml) and low-dose (1.76 mg\/ml) formulations of TFV enemas were evaluated for systemic uptake in blood, colorectal biopsy specimens, and rectal CD4\n            <jats:sup>+<\/jats:sup>\n            T cells. Markedly higher TFV concentrations were observed in plasma and tissues after administration of the HOsm high-dose formulation than with all other formulations tested. TFV and TFV diphosphate (TFV-DP) concentrations in tissue correlated for the HOsm high-dose formulation, demonstrating rapid uptake and transformation of TFV to TFV-DP in tissues. TFV-DP amounts in tissues collected at 1 and 24 h were 7 times and 5 times higher, respectively (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01), than the ones collected in tissues with the IOsm formulation. The HOsm high-dose formulation prevented infection in\n            <jats:italic>ex vivo<\/jats:italic>\n            challenges of rectal tissues collected at 1, 24, and 72 h after the intrarectal dosing, whereas the same TFV dose formulated as an IOsm enema was less effective.\n          <\/jats:p>","DOI":"10.1128\/aac.01644-17","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T15:50:37Z","timestamp":1509378637000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Hypo-osmolar Formulation of Tenofovir (TFV) Enema Promotes Uptake and Metabolism of TFV in Tissues, Leading to Prevention of SHIV\/SIV Infection"],"prefix":"10.1128","volume":"62","author":[{"given":"Peng","family":"Xiao","sequence":"first","affiliation":[{"name":"New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjeev","family":"Gumber","sequence":"additional","affiliation":[{"name":"Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Marzinke","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhijit A.","family":"Date","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Ophthalmology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuy","family":"Hoang","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Hanes","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Ensign","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Ophthalmology, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Chemical &amp; Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Magee's Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Rohan","sequence":"additional","affiliation":[{"name":"Magee's Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J.","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francois","family":"Villinger","sequence":"additional","affiliation":[{"name":"New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global AIDS update 2016","author":"UNAIDS","year":"2016","unstructured":"UNAIDS. 2016. Global AIDS update 2016. UNAIDS, Geneva, Switzerland."},{"key":"e_1_3_3_3_2","volume-title":"Prevention gap report, 2016","author":"UNAIDS","year":"2016","unstructured":"UNAIDS. 2016. Prevention gap report, 2016. UNAIDS, Geneva, Switzerland."},{"key":"e_1_3_3_4_2","unstructured":". 2015. Diagnoses of HIV infection in the United States and dependent areas. HIV surveillance report 2016 vol 27. http:\/\/www.cdc.gov\/hiv\/library\/reports\/hiv-surveillance.html. 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