38 research outputs found

    Randomised clinical trial: Alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

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    Background Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. Aim To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Methods Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. Results A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Conclusions Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens

    Randomised clinical trial: Alisporivir combined with peginterferon and ribavirin in treatment-na\uefve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

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    BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. AIM: To evaluate efficacy and safety of ALV plus peginterferon-\u3b12a and ribavirin (PR) in treatment-na\uefve patients with chronic HCV genotype 1 infection. METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received 6512 weeks and 20% had received 6524 weeks of ALV/PR triple therapy. RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-na\uefve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens

    Evaluation of Estimated Glomerular Filtration Rate During Continuous 4-Year Treatment with Telbivudine in Patients with Bridging Fibrosis/Cirrhosis

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    Fulltext of the abstract in: http://www.professionalabstracts.com/ilc2014/planner/index.php?go=abstract&action=abstract_show&absno=1040&Poster presentationSession 7C: Viral Hepatitis: Hepatitis B & D - Clinical (Therapy, New Compounds, Resistance

    Decline in pulmonary function during chronic hepatitis C virus therapy with modified interferon alfa and ribavirin

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    Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFN\u3b1-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFN\u3b1-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 \u3bcg q4wk or Peg-IFN\u3b1-2a 180 \u3bcg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines ( 6515%) were observed in 173 patients (48%), and were more frequent with Peg-IFN\u3b1-2a and albIFN 1500 \u3bcg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFN\u3b1-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFN\u3b1/ribavirin therapy and commonly persisted for 656 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research

    Randomized trial of albinterferon alfa-2b every 4 weeks for chronic hepatitis C virus genotype 2/3

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    Albinterferon alfa-2b (albIFN) is a fusion protein of recombinant human albumin/recombinant interferon (IFN)-\u3b1-2b, with 3c200-h half-life. Safety/efficacy of albIFN q4wk was evaluated in 391 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to one of four open-label treatment groups: pegylated IFN (Peg-IFN)-\u3b1-2a 180 \u3bcg qwk or albIFN 900, 1200 or 1500 \u3bcg q4wk, plus oral ribavirin 800 mg/day, for 24 weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <20 IU/mL 24 weeks post-treatment). SVR rates were as follows: 85%, 76%, 76% and 78% with Peg-IFN\u3b1-2a and albIFN 900, 1200 and 1500 \u3bcg, respectively (P = NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4) were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not influenced by interleukin 28B genotype, although rapid virologic response rates were greater with interleukin 28B CC (P = NS). Serious adverse event rates were as follows: 4%, 11%, 3% and 3% with Peg-IFN\u3b1-2a and albIFN 900, 1200 and 1500 \u3bcg, respectively. No increase in serious/severe respiratory events was noted with albIFN. Fewer absolute neutrophil count reductions <750/mm(3) occurred with albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions <10 g/dL were less frequent with albIFN 900 and 1200 \u3bcg vs 1500 \u3bcg and Peg-IFN\u3b1-2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN administered q4wk produced fewer haematologic reductions than Peg-IFN\u3b1-2a, but had numerically lower SVR rates (P = NS) in patients with chronic HCV genotype 2/3

    Diverse Contexts of Zoonotic Transmission of Simian Foamy Viruses in Asia

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    In Asia, contact between persons and nonhuman primates is widespread in multiple occupational and nonoccupational contexts. Simian foamy viruses (SFVs) are retroviruses that are prevalent in all species of nonhuman primates. To determine SFV prevalence in humans, we tested 305 persons who lived or worked around nonhuman primates in several South and Southeast Asian countries; 8 (2.6%) were confirmed SFV positive by Western blot and, for some, by PCR. The interspecies interactions that likely resulted in virus transmission were diverse; 5 macaque taxa were implicated as the source of infection. Phylogenetic analysis showed that SFV from 3 infected persons was similar to that from the nonhuman primate populations with which the infected persons reported contact. Thus, SFV infections are likely to be prevalent among persons who live or work near nonhuman primates in Asia
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