ÿþ<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd"> <html> <head> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <title>EASL 2010 - Poster Presentations</title> <link rel="stylesheet" type="text/css" href="style.css"> </head> <body> <table width="750" align="center" border="0" cellspacing="0" cellpadding="0" class="MainTable"> <tr> <td><img src="http://www2.kenes.com/liver-congress/PublishingImages/top_ei.jpg" width="760" height="129" /></td> </tr> <tr> <td class="content"><h1>Poster Presentations</h1> <P><b>Session Title:</b> Category 5e. VIRAL HEPATITIS: e. HEPATITIS B - CLINICAL (THERAPY NEW COMPOUNDS, RESISTANCE)<br><b>Presentation Date:</b> Apr 17, 2010</P><h2 align='left'><B>EFFICACY OF TENOFOVIR DF TREATMENT IN PATIENTS WITH A SUBOPTIMAL RESPONSE TO ADEFOVIR DIPIVOXIL</B></h2> <p align='left'><b>M. Manns</b><sup>1</sup>*, J. Heathcote<sup>2</sup>, P. Marcellin<sup>3</sup>, T. Berg<sup>4</sup>, J. Anderson<sup>5</sup>, J. Sorbel<sup>5</sup>, D. Frederick<sup>5</sup>, F. Rousseau<sup>5</sup>, K. Borroto-Esoda<sup>5</sup><br> <em><sup>1</sup>Medizinische Hochschule Hannover, Hannover, Germany, <sup>2</sup>University of Toronto, Toronto, ON, Canada, <sup>3</sup>Hopital Beaujon, Clichy, France, <sup>4</sup>Medizinische Klink mit Schwerpunkt, Humboldt-Universität, Berlin, Germany, <sup>5</sup>Gilead Sciences, Inc, Durham, NC, USA. *manns.michael@mh-hannover.de</em></p><br> <p align='justify'><b><b>Background and aims: </b> </b>Tenofovir disoproxil fumarate (TDF) has demonstrated potent activity in HBeAg positive and negative, treatment-naïve and lamivudine-experienced, CHB patients. In vitro studies have shown varying degrees of sensitivity to tenofovir against different patterns of adefovir-associated resistance mutations. The aim of this analysis was to evaluate the activity of TDF in patients with suboptimal antiviral efficacy (HBV DNA >400 copies/mL) on adefovir dipivoxil (ADV) therapy.<br><b><b>Methods: </b> </b>160 HBeAg+ and HBeAg- patients with persistent viral replication after 24-96 weeks of ADV therapy were treated with TDF for up to 96 weeks in studies GS-US-174-0102, GS-US-174-0103, and GS-US-174-0106; 23% had prior lamivudine experience. HBV DNA, HBsAg, HBeAg and ALT were routinely monitored; population sequencing of HBV polymerase was conducted at baseline and for patients with HBV DNA >400 copies/mL at week 96/last on treatment. An ITT analysis was conducted using non-completers=failures. Per protocol, patients with confirmed HBV DNA e"400 copies/mL could opt to add emtricitabine (FTC); patients were considered failures after FTC addition. <br><b><b>Results: </b> </b>Overall, 77% of patients had HBV DNA < 400 copies/mL and 59% had normal ALT after 24 weeks of TDF monotherapy and this was maintained through 96 weeks; similar results were observed among patients with lamivudine-resistance (n=7) and adefovir resistance (n=10) mutations at baseline. Among the 101 HBeAg+ patients, 15% experienced HBeAg loss and 10% experienced HBeAg seroconversion. The Kaplan-Meier estimate for HBsAg loss and seroconversion over 96 weeks was 4.5% and 3.2%; 6 Caucasian/genotypes A/D and 1 Asian/genotype C. No patient discontinued due to an adverse event and 2 patients experienced SAEs considered related to TDF (ALT increased). Two patients experienced a 0.5 mg/dL increase in creatinine and remained on TDF treatment following dose reduction. No patient experienced a decrease in creatinine clearance to < 50 mL/min. No amino acid substitutions associated with TDF resistance developed through 96 weeks.<br><b><b>Conclusions: </b> </b>Complete viral suppression was observed following up to 96 weeks of TDF monotherapy in the majority of patients with incomplete viral suppression on ADV; including those with prior lamivudine use. The safety and tolerability profile of TDF was good and no resistance to TDF was observed.</p> <br><a href='Session-P03-5e.htm'>Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>