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Background: The diagnosis of chronic hepatitis C virus infection is based on nucleic acid testing (NAT) for HCV-RNA. We evaluated whether total HCV core antigen testing could be a substitute for NAT testing. Patients and Methods: Samples from 192 untreated chronic HCV positive patients previously tested for HCV-RNA by four different commercially available assays (Super-Quant, Amplicor HCV Monitor v 1.0 and v 2.0, Quantiplex) were tested for total HCV core antigen using the Ortho trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ, USA). Furthermore, 52 HCV-RNA positive paired serum and plasma samples were analysed. Finally, inter-assay coefficients of variation for core antigen were determined by repeated testing of 59 samples. Results: 172/192 (89.6%) samples from untreated HCV patients showed positive results with the trak-C assay. Importantly, all but two trak-C positive samples were NAT positive. Only four of the twenty trak-C negative samples tested positive by two NAT assays with viral loads below 30,000 copies/mL. Moreover, HCV core antigen levels correlated significantly with HCV-RNA levels (r > 0.72; p > 0.001), gave consistent results in paired serum and plasma samples (r = 0.991), and showed a very low inter-assay variability (r=0.943) independent of genotype. Conclusion: Based on the performance characteristics, easiness of use, and potential lower cost of the core Ag assay, we propose an alternative testing algorithm for establishing the diagnosis of chronic HCV infection in which the trak-C assay could substitute for NAT as the first choice for detection of HCV viraemia in anti-HCV positive individuals. NAT would only be necessary in rare cases with low viral load.

Introduction This Phase 3 study evaluated telaprevir (T) in combination with pegylated-IFN alfa-2a (P) and ribavirin (R) in well-characterised G1 prior-PR treatment failure patients including prior PR non-responders (null and partial) and relapsers. Method REALIZE was a randomised, international, multicentre, double-blind, placebo-controlled trial evaluating efficacy, safety and tolerability of T (750 mg q8 h) plus P (180μg/w) and R (1000–1200 mg/d) compared with PR alone. The treatment arms (randomised 2:2:1, stratified by viral load and prior response) were: 12-weeks T/PR, followed by 36-weeks PR (T12PR48); 4-weeks PR followed by 12 weeks T/PR (T delayed start, DS), then 32-weeks PR (T12(DS)/PR48); 48-weeks PR (Pbo/PR48). The primary objective was efficacy of the T/PR arms in non-responders and relapsers. Secondary objectives included evaluation of T DS and efficacy in prior-null and -partial responders. HCV RNA was quantified using COBAS TaqManAE v2.0 assay (LLOQ=25 IU/ml). Results 833 patients were screened, and 662 treated. 70% of patients were male, 93% Caucasian, 26% had cirrhosis, and 89% had baseline HCV RNA ≥800 000 IU/ml. AEs reported more frequently in T arms were rash, pruritus, diarrhoea, anorectal disorders and anaemia. 13% of T/PR patients had premature discontinuation (D/C) of T due to AEs: rash (4%) and anaemia (3%) were the most common AEs leading to T D/C. Conclusion T/PR SVR was significantly superior to PR in all prior-treatment failure populations including null- and partial-responders. A telaprevir delayed start did not have a significant impact on SVR rates. Safety profile of T/PR was consistent with that observed in treatment naive subjects.

treatment, discontinued therapy due to an AE. No AE leading to discontinuation occurred in >1 patient. Hemoglobin

289 DISCREPANCIES BETWEEN DEFINITIONS OF NULL RESPONSE TO TREATMENT WITH PEGINTERFERON-ALFA-2A AND RIBAVIRIN: IMPLICATIONS FOR NEW HCV DRUG DEVELOPMENT G. Picchio, D. Luo, S. George, A. Kwong, T. Kieffer, J. Mc Hutchison, J.-M. Pawlotsky. Tibotec, Inc, Yardley, PA, Vertex Pharmaceuticals Incorporated, Cambridge, MA, Duke University Medical Center, Durham, NC, USA; Hopital Henri Mondor, Creteil, France E-mail: gpicchio@its.jnj.com

To understand the origin and past dissemination of human T-cell leukemia/lymphotropic virus type I (HTLV-I) in Latin America, we conducted a phylogenetic study of five new HTLV-I isolates from Argentina. We sequenced partial fragments of long terminal repeats (LTR) of the new HTLV-Is, and then the sequences were subjected to a phylogenetic analysis for comparison with other HTLV-Is of various geographical origins. Our results indicated that all the isolates were members of the Cosmopolitan group. Furthermore, most (four out of five isolates) of the new HTLV-Is belonged to the Transcontinental (A) subgroup, the most widespread subgroup of the four subgroups in the Cosmopolitan group. In this subgroup, they were closely related to HTLV-Is found in other South American countries including those of Amerindians, and were different from those found in Africa. In contrast, the remaining one HTLV-I (ARGMF) did not show any clear similarity to known HTLV-I isolates belonging to the Cosmopolitan group. The close similarity of South American HTLV-Is strongly suggests a common origin of the virus in this continent. Our results do not support the proposed idea of recent introduction of HTLV-I into South America as a consequence of the slave trade from Africa, where phylogenetically different HTLV-Is predominate.

9 TMC435 IN PATIENTS INFECTED WITH HCV GENOTYPE 1 WHO HAVE FAILED PREVIOUS PEGYLATED INTERFERON/RIBAVIRIN TREATMENT: VIROLOGIC ANALYSES OF THE ASPIRE TRIAL O. Lenz, B. Fevery, L. Vijgen, J. Verbeeck, M. Peeters, M. Beumont-Mauviel, S. Zeuzem, G. Picchio. Clinical Virology, Tibotec BVBA, Beerse, Belgium, J.W. Goethe University Hospital, Frankfurt, Germany, Tibotec Inc., Yardley, PA, USA E-mail: olenz@its.jnj.com

5 REALIZE TRIAL FINAL RESULTS: TELAPREVIR-BASED REGIMEN FOR GENOTYPE 1 HEPATITIS C VIRUS INFECTION IN PATIENTS WITH PRIOR NULL RESPONSE, PARTIAL RESPONSE OR RELAPSE TO PEGINTERFERON/RIBAVIRIN S. Zeuzem, P. Andreone, S. Pol, E.J. Lawitz, M. Diago, S. Roberts, R. Focaccia, Z.M. Younossi, G.R. Foster, A. Horban, P.J. Pockros, R. Van Heeswijk, S. de Meyer, D. Luo, G. Picchio, M. Beumont. Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; Universita di Bologna, Bologna, Italy; Universite Paris Descartes, INSERM Unite 567, and Assistance Publique-Hopitaux de Paris, Cochin Hospital, Paris, France; Alamo Medical Resarch, San Antonio, TX, USA; Hospital General de Valencia, Valencia, Spain; Department of Gasteroenterology, Alfred Hospital, Melbourne, VIC, Australia; Emilio Ribas Infectious Diseases Institute, Sao Paulo, Brazil; Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA, USA; Institute of Cell and Molecular Science, Queen Mary University of London, London, UK; Medical University of Warsaw, Warsaw, Poland; Scripps Clinic and The Scripps Research Institute, La Jolla, CA, USA; Tibotec BVBA, Beerse, Belgium; Tibotec Inc., Titusville, NJ, USA E-mail: zeuzem@em.uni-frankfurt.de Background: The Phase 3 study REALIZE evaluated telaprevir (T) in combination with pegylated-IFN alfa-2a (P) and ribavirin (R) in well-characterised prior PR treatment-failure patients. Methods: REALIZE was a randomised, international, multicentre, double-blind, placebo-controlled trial to evaluate the efficacy, safety and tolerability of T (750mg q8h) plus P (180mg/w) and R (1000– 1200mg/d) compared with PR alone in G1 HCV-infected patients with prior PR treatment failure including non-responders (nulland partial-responders) and relapsers. The treatment arms (randomised 2:2:1, stratified by viral load and type of prior response) were: 1) T/PR for 12 weeks, followed by PR for 36 weeks (T12/PR48); 2) PR for 4 weeks followed by T/PR for 12 weeks, then PR for 32 weeks (Lead-in T12/PR48); 3) PR for 48 weeks (Pbo/PR48). The primary objective was to evaluate the superior efficacy of the T/PR arms for non-responders and relapsers. Secondary objectives included the evaluation of a lead-in and efficacy in prior nulland partialresponders separately. HCVRNA was quantified with the COBAS TaqMan v2.0 assay (LLOQ=25 IU/mL). ESAs were not allowed for anaemia management. Results: 833 patients were screened, 663 randomised, and 662 treated. 70% of patients were male, 93% were Caucasian, 26% had cirrhosis, and 89% had baseline HCVRNA ≥800,000 IU/mL.

251 GENOTYPIC AND PHENOTYPIC CHARACTERIZATION OF GENOTYPE 2/3 HCV VARIANTS IN PATIENTS TREATED WITH TELAPREVIR ALONE OR IN COMBINATION WITH PEGINTERFERON ALFA-2A/RIBAVIRIN IN STUDY C209 S. De Meyer, G.R. Foster, A. Ghys, M. Beumont, B. Van Baelen, T.-I. Lin, G. Picchio. Tibotec BVBA, Mechelen, Belgium; Queen Mary University of London, Institute of Cell and Molecular Science, London, UK; Tibotec Inc, Yardley, PA, USA E-mail: sdmeyer@its.jnj.com

289 DISCREPANCIES BETWEEN DEFINITIONS OF NULL RESPONSE TO TREATMENT WITH PEGINTERFERON-ALFA-2A AND RIBAVIRIN: IMPLICATIONS FOR NEW HCV DRUG DEVELOPMENT G. Picchio, D. Luo, S. George, A. Kwong, T. Kieffer, J. Mc Hutchison, J.-M. Pawlotsky. Tibotec, Inc, Yardley, PA, Vertex Pharmaceuticals Incorporated, Cambridge, MA, Duke University Medical Center, Durham, NC, USA; Hopital Henri Mondor, Creteil, France E-mail: gpicchio@its.jnj.com