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Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV.A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 microg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per milliliter at the end of follow-up, at week 72).The overall rate of sustained virologic response was significantly higher among the recipients of peginterferon alfa-2a plus ribavirin than among those assigned to interferon alfa-2a plus ribavirin (40 percent vs. 12 percent, P0.001), or peginterferon alfa-2a plus placebo (40 percent vs. 20 percent, P0.001). Among patients infected with HCV genotype 1, the rates of sustained virologic response were 29 percent with peginterferon alfa-2a plus ribavirin, 14 percent with peginterferon alfa-2a plus placebo, and 7 percent with interferon alfa-2a plus ribavirin. The corresponding rates among patients infected with HCV genotype 2 or 3 were 62 percent, 36 percent, and 20 percent. Neutropenia and thrombocytopenia were more common among patients treated with regimens that contained peginterferon alfa-2a, and anemia was more common among patients treated with regimens containing ribavirin.Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy.

Background: Despite a rapid evolution in the treatment of Hepatitis C (HCV), response to therapy among different racial and ethnic groups is poorly characterized. Study: Three hundred and thirty HCV infected patients naive to previous therapy received induction therapy followed by every other day dosing with consensus interferon. Greater than 30% of treated patients were not white, allowing comparison of response among different races/ethnicities and genotypes. Results: An overall sustained virologic response (SVR) was achieved in 24% of white, 12% of Hispanic, and 4% of AA patients (P = 0.003 white vs. non-white). 15% of white and 13% of Hispanic Genotype 1 patients achieved an SVR; 2% of AA patients achieved an SVR (P = 0.001 AA vs. non AA). Surprisingly, an SVR of 50% and 40% was achieved by AA and White Genotype 2 patients, compared with 10% in Hispanic patients (P = 0.001). Conclusion: Significant differences in response rates to induction therapy followed by every other day dosing with consensus Interferon was observed when comparing white to non-white patients, particularly when comparing response rates by genotype. These observations reinforce the requirement that prospective studies that enroll a significant percentage of non-whites are needed to adequately characterize response rates to anti-HCV directed therapy.

were genotyped for SLC28A2 rs11854484 C>T, SLC28A3 rs56350726 A>T and SLC28A3 rs10868138 T>C as well as ITPA polymorphisms rs1127354 C>A and rs7270101 A>C. RBV serum levels during treatment were measured in 49 patients at week 4 and 8. Results: 96 of 178 patients (53.9%) in our study achieved SVR. The SLC28A3 rs56350726 TT genotype (vs. AT/AA; p =0.03) and the T allele (vs. A; p = 0.02) were both associated with increased SVR rate. No such association with therapy outcome was found for SLC28A2 rs11854484 or SLC28A3 rs10868138 as well as ITPA rs1127354 and rs7270101 and genotype combinations thereof (ITPA function 0–+++). Association between the SLC28A2 rs11854484 polymorphism and dosageand body weight-adjusted RBV-levels showed significantly higher RBV-levels at weeks 4 (p =0.06) and 8 (p =0.02) for the genotype TT compared to TC or CC genotype. Conclusion: Our results show a genetic association between the SLC28A3 polymorphism rs56350726 and therapeutic outcome. This particular polymorphism represents a genetic host factor which affects RBV uptake and consecutively SVR and hemolytic anemia. Association between RBV serum levels and SLC28A2 rs11854484 are first described and enhance the need for further studies investigating RBV-pharmacokinetic for individualized treatment.

1359 FIRST SVR DATA WITH THE NUCLEOSIDE ANALOGUE POLYMERASE INHIBITOR MERICITABINE (RG7128) COMBINED WITH PEGINTERFERON/RIBAVIRIN IN TREATMENT-NAIVE HCV G1/4 PATIENTS: INTERIM ANALYSIS FROM THE JUMP-C TRIAL P. Pockros, D. Jensen, N. Tsai, R.M. Taylor, A. Ramji, C. Cooper, R. Dickson, A. Tice, S. Stancic, D. Ipe, J.A. Thommes, J.M. Vierling. Scripps Clinic Research Center, La Jolla, CA, Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL, Hawaii Medical Center, Honolulu, HI, The University of Kansas Hospital Medical Center, Kansas City, KS, USA; Division of Gastroenterology, University of British Columbia, Vancouver, BC, The Ottawa Hospital, Ottowa, ON, Canada; Dartmouth-Hitchcock Medical Center, Lebanon, NH, Infections Limited Hawaii, Honolulu, HI, Roche, Nutley, NJ, Genentech, South San Francisco, CA, Baylor College of Medicine, Houston, TX, USA E-mail: pockros.paul@scrippshealth.org Introduction: Mericitabine (RG7128, MCB) is a potent, selective nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase with activity across all HCV genotypes. MCB has demonstrated a high barrier to resistance without treatmentemergent resistance observed to date. Methods: JUMP-C is an ongoing randomised, double-blind, placebocontrolled phase 2b study in treatment naive patients infected with HCV G1/4. The trial objective was to compare a response guided therapy regimen of MCB plus peginterferon alfa-2a/ribavirin (P/R) with P/R alone. Patients randomised to arm A achieving an extended RVR (eRVR; HCVRNA

IMPORTANCE: Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon. OBJECTIVE: To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment. DESIGN, SETTING, AND PARTICIPANTS: Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants. INTERVENTIONS: Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcomewas the proportion of patients with SVR (serum HCV

4029 Background: TRAIL is a member of the tumor necrosis factor ligand super family that induces programmed cell death primarily in tumor cells (including liver tumors) through TRAIL death receptor...

Background: The efficacy of sofosbuvir (SOF)-containing regimens in patients who failed to achieve sustained virologic response (SVR) with SOF remains unknown. Given the lack of genotypic or phenotypic resistance to SOF in patients who did not achieve an SVR in the Phase 3 program, we designed an open-label study for relapsers to receive either a longer duration of SOF + RBV (24 weeks) or SOF + RBV with peginterferon (PEG-IFN). Methods: GT-2 and GT-3 HCV infected patients who failed either 12or 16-week regimens of SOF + RBV (Phase 3 studies: FISSION, FUSION, and POSITRON) were offered either 12-weeks of SOF (400 mg once daily) + PEG-IFN (180μg weekly) + RBV (1000-1200 mg daily) or an interferon-free 24-week arm of SOF+RBV. The choice of regimen was based upon investigator discretion. The primary efficacy endpoint is SVR12 and the secondary efficacy endpoint is SVR4. Results: A total of 97 GT-3 and 16 GT-2 patients have been enrolled. The majority of patients were male (80%) with a non-IL28CC genotype (65%) and 33% of patients had cirrhosis. To date, overall SVR4 rates are 96% (27/28) for GT-3 and 100% (6/ 6) for GT-2 infected patients. The table displays these data for patients who have reached the 4-week post-treatment visit. Conclusions: Retreatment with sofosbuvir regimens of longer duration or with the addition of PEG-IFN in prior SOF failures results in high SVR4 rates and appears to offer a viable approach for GT-2 or GT-3 HCV infected patients who fail to achieve an SVR with SOF+RBV regimens.

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

1205 PRELIMINARY EVALUATION OF A NEW AUTOPHAGY INHIBITOR ANTIVIRAL AGENT FOR HEPATITIS C VIRUS IN AN EX VIVO MODEL OF HUMAN LIVER SLICES CULTURE S. Lagaye, H. Shen, J. Gaston, G. Rousseau, P.-P. Massault, A. Vallet-Pichard, P. Sogni, V. Mallet, J. Courcambeck, S. Brun, F. Bassisi, C. Camus, P. Halfon, S. Pol. Equipe «Cycle Cellulaire, Regeneration et Hepatopathies», Institut Cochin, INSERM U1016, CNRS UMR 8104, Universite Paris Descartes (UMR S1016), Paris, France; APHP, Groupe Hospitalier La Pitie Salpetriere, Service de Chirurgie Digestive et Hepato Bilio Pancreatique, APHP, Groupe Hospitalier Cochin-Hotel Dieu, Service de Chirurgie Viscerale, APHP, Groupe Hospitalier Cochin-Hotel Dieu, Unite d’Hepatologie, Paris, GenosciencePharma, Marseille, France E-mail: sylvie.lagaye@inserm.fr

13.6±1.8 g/dL [8.8–17.5], respectively. After 12W, a complete early virological response was obtained in 34 (83%) boceprevir patients and in 35 (61%) telaprevir patients (p = 0.026). Among 17 boceprevir and 16 telaprevir patients, 14 (82%) and 7 (43%) achieved an end of treatment response (EOT) with an undetetectable viral load, respectively (p = 0.032). Among 9 boceprevir and 5 telaprevir patients, 6 and 1 achieved SVR12, respectively. Among 6 patients in the boceprevir group, 3 achieved SVR24. In the telaprevir group, 29 patients discontinued therapy (serious adverse events, n = 13; virological breakthrough, n = 6; non-response, n = 9). In the boceprevir group, 14 patients discontinued therapy (serious adverse events, n = 5; virological breakthrough, n = 2; non-response, n = 4; retransplantation, n = 1). Four patients died in a context of infectious disorders: boceprevir, n = 2 (W20/W24); telaprevir, n = 2 (W2/W9). The most common side effect was anemia in 85% of patients: 95% and 96% in boceprevir and telaprevir groups received erythropoietin alone or combined with ribavirin dose reduction. Conclusion: In liver transplanted patients, EOT rate was 82% and 38% with boceprevir and telaprevir, respectively. Among the overall population, 44% of patients discontinued therapy because of treatment failure or occurrence of serious adverse events.

1421 HIGH SUSTAINED VIROLOGIC RESPONSE RATE IN TREATMENT-NAIVE HCV GENOTYPE 1A AND 1B PATIENTS TREATED FOR 12 WEEKS WITH AN INTERFERON-FREE ALL-ORAL QUAD REGIMEN: INTERIM RESULTS M. Sulkowski, M. Rodriguez-Torres, E. Lawitz, M. Shiffman, S. Pol, R. Herring, J. McHutchison, P. Pang, D. Brainard, D. Wyles, F. Habersetzer. Johns Hopkins University School of Medicine, Lutherville, MD, Fundacion de Investigacion de Diego, Santurce, PR, Alamo Medical Research, San Antonio, TX, Liver Institute of Virginia, Richmond, VA, USA; Hopital Necker, Paris, France; Nashville Gastrointestinal Specialists, Inc., Nashville, TN, Gilead Sciences, Inc., Foster City, University of California, San Diego, La Jolla, CA, USA; Hopitaux Universitaires de Strasbourg, Strasbourg, France E-mail: msulkowski@jhmi.edu

1421 HIGH SUSTAINED VIROLOGIC RESPONSE RATE IN TREATMENT-NAIVE HCV GENOTYPE 1A AND 1B PATIENTS TREATED FOR 12 WEEKS WITH AN INTERFERON-FREE ALL-ORAL QUAD REGIMEN: INTERIM RESULTS M. Sulkowski, M. Rodriguez-Torres, E. Lawitz, M. Shiffman, S. Pol, R. Herring, J. McHutchison, P. Pang, D. Brainard, D. Wyles, F. Habersetzer. Johns Hopkins University School of Medicine, Lutherville, MD, Fundacion de Investigacion de Diego, Santurce, PR, Alamo Medical Research, San Antonio, TX, Liver Institute of Virginia, Richmond, VA, USA; Hopital Necker, Paris, France; Nashville Gastrointestinal Specialists, Inc., Nashville, TN, Gilead Sciences, Inc., Foster City, University of California, San Diego, La Jolla, CA, USA; Hopitaux Universitaires de Strasbourg, Strasbourg, France E-mail: msulkowski@jhmi.edu

fed and 100mg, 300mg and 900mg administered fasted and at BID doses of 450mg and 900mg administered fed. A solution formulation (450mg BID) was administered in an additional cohort. Each cohort consisted of 8 active and 2 placebo control subjects. Plasma HCVRNA, resistance surveillance and pharmacokinetic (GS6620 and primary metabolites) samples were collected throughout the dosing period. Results: Few treatment related adverse events were observed (n =12) with all but one being mild. Headache (n =4) was the most frequent adverse event. No treatment-related severe adverse events, discontinuations or other safety signals were noted during dosing or the 14 day follow-up period. The greatest antiviral activity was observed in cohorts administering 450mg and 900mg doses BID.

58 FINAL RESULTS – RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED SAFETY, ANTI-VIRAL PROOF-OF-CONCEPT STUDY OF MIRAVIRSEN, AN OLIGONUCLEOTIDE TARGETING MIR-122, IN TREATMENT-NAIVE PATIENTS WITH GENOTYPE 1 CHRONIC HCV INFECTION H.W. Reesink, H.L.A. Janssen, S. Zeuzem, E. Lawitz, M. Rodriguez-Torres, K. Patel, A. Chen, C. Davis, B. King, A. Levin, M.R. Hodges. Department of Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Medicine, J.W. Goethe University Hospital, Frankfurt/Main, Germany; Alamo Medical Research, San Antonio, TX, Fundacion de Investigacion, San Juan, PR, Duke University, Durham, NC, Santaris Pharma, San Diego, CA, USA E-mail: h.w.reesink@amc.nl