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The current study investigated the\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    efficacy of tenofovir disoproxil fumarate (TDF) and\/or emtricitabine [(\u2212)-FTC] alone and in combination therapy for HBV infection utilizing the HepAD38 system (human hepatoblastoma cells transfected with HBV). Cellular pharmacology studies demonstrated increased levels of (\u2212)-FTC triphosphate with coincubation of increasing concentrations of TDF, while (\u2212)-FTC had no effect on intracellular tenofovir (TFV) diphosphate levels. Quantification of extracellular HBV by real-time PCR from hepatocytes demonstrated the anti-HBV activity with TDF, (\u2212)-FTC, and their combination. Combination of (\u2212)-FTC with TDF or TFV (ratio, 1:1) had a weighted average combination index of 0.7 for both combination sets, indicating synergistic antiviral effects. No cytotoxic effects were observed with any regimens. Using an\n                    <jats:italic>in vivo<\/jats:italic>\n                    murine model which develops robust HBV viremia in nude mice subcutaneously injected with HepAD38 cells, TDF (33 to 300 mg\/kg of body weight\/day) suppressed virus replication for up to 10 days posttreatment. At 300 mg\/kg\/day, (\u2212)-FTC strongly suppressed virus titers to up to 14 days posttreatment. Combination therapy (33 mg\/kg\/day each drug) sustained suppression of virus titer\/ml serum (&lt;1 log\n                    <jats:sub>10<\/jats:sub>\n                    unit from pretreatment levels) at 14 days posttreatment, while single-drug treatments yielded virus titers 1.5 to 2 log units above the initial virus titers. There was no difference in mean alanine aminotransferase values or mean wet tumor weights for any of the groups, suggesting a lack of drug toxicity. TDF\u2013(\u2212)-FTC combination therapy provides more effective HBV suppression than therapy with each drug alone.\n                  <\/jats:p>","DOI":"10.1128\/aac.01483-12","type":"journal-article","created":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T01:02:59Z","timestamp":1347930179000},"page":"6186-6191","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Evaluation of Single and Combination Therapies with Tenofovir Disoproxil Fumarate and Emtricitabine\n                    <i>In Vitro<\/i>\n                    and in a Robust Mouse Model Supporting High Levels of Hepatitis B Virus Replication"],"prefix":"10.1128","volume":"56","author":[{"given":"Raymond F.","family":"Schinazi","sequence":"first","affiliation":[{"name":"Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine\/Veterans Affairs Medical Center, Decatur, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Bassit","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine\/Veterans Affairs Medical Center, Decatur, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia M.","family":"Clayton","sequence":"additional","affiliation":[{"name":"Department of Biology, Temple University, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biology, Temple University, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Kohler","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine\/Veterans Affairs Medical Center, Decatur, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr","family":"Obikhod","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine\/Veterans Affairs Medical Center, Decatur, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla","family":"Arzumanyan","sequence":"additional","affiliation":[{"name":"Department of Biology, Temple University, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Feitelson","sequence":"additional","affiliation":[{"name":"Department of Biology, Temple University, Philadelphia, Pennsylvania, USA"},{"name":"Center for Biotechnology, Temple University, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11045-11052.2005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.2.380"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1055\/s-2006-939758","article-title":"Antiviral drug resistance: clinical consequences and molecular aspects","volume":"26","author":"Bartholomeusz A","year":"2006","unstructured":"BartholomeuszA LocarniniSA. 2006. 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