***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: BACKGROUND New direct-acting antiviral agents are currently being developed to treat chronic HCV . The efficacy and safety of daclatasvir combined with peginterferon alfa-2a ( alfa-2a ) and ribavirin were assessed in a r and omized , double-blind Phase IIa study of Japanese patients with chronic HCV genotype-1 infection . METHODS Japanese patients who were treatment-naive ( n=25 ) or prior null ( n=12 ) or partial ( n=5 ) responders received once-daily daclatasvir 10 mg or 60 mg or placebo in combination with alfa-2a and ribavirin . Daclatasvir recipients with a protocol -defined response ( HCV RNA<15 IU/ml at week 4 and undetectable at week 12 ) were treated for 24 weeks ; placebo recipients and patients without a protocol -defined response were treated for 48 weeks . RESULTS Sustained virological response at 24 weeks post-treatment ( SVR24 ) was achieved by 89 % and 100 % of treatment-naive patients receiving daclatasvir 10 mg and 60 mg , respectively , versus 75 % in placebo recipients . Virological failure was more frequent in prior non-responder patients , with 50 % and 78 % achieving SVR24  in daclatasvir 10 mg and 60 mg groups , respectively . Adverse events occurred with similar frequency among treatment groups and were consistent with the adverse event profile of alfa-2a/ribavirin alone . The most commonly reported adverse events included pyrexia , alopecia , anaemia , lymphopenia , neutropenia , pruritus and diarrhoea . Three patients discontinued treatment due to anaemia . CONCLUSIONS Daclatasvir combined with alfa-2a/ribavirin in treatment-naive patients showed greater efficacy than alfa-2a/ribavirin alone and was generally well tolerated . The 60-mg dose of daclatasvir achieved the highest rates of SVR24 in both treatment-naive and non-responder population s and will be evaluated in a Phase III clinical trial BACKGROUND & AIMS Improved therapies for peginterferon/ribavirin null or partial responders are needed . This study evaluated daclatasvir ( NS5A inhibitor ) and asunaprevir ( NS3 protease inhibitor ) plus peginterferon alfa-2a and ribavirin in this patient population . METHODS This open-label , phase 3 study ( HALLMARK-QUAD ; NCT01573351 ) treated patients with chronic hepatitis C virus ( HCV ) genotype 1 ( n=354 ) or 4 ( n=44 ) infection who had a prior null or partial response to peginterferon/ribavirin . Patients received daclatasvir 60 mg once-daily plus asunaprevir 100 mg twice-daily , with weekly peginterferon alfa-2a and weight-based ribavirin for 24 weeks . The primary endpoint was sustained virological response at post-treatment week 12 ( SVR12 ) among genotype 1-infected patients . RESULTS Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93 % ( 95 % CI 90 - 96 ) in prior non-responders infected with HCV genotype 1 . SVR12 rates among genotype 4-infected patients were 98 % ( 95 % CI 93 - 100 ) ; one patient had a missing post-treatment week-12 HCV-RNA measurement , but achieved an SVR at post-treatment week 24 , yielding a 100 % SVR rate in genotype 4 patients . Prior peginterferon/ribavirin response , sex , age , IL28B genotype , or cirrhosis status did not influence SVR12 rates . Serious adverse events occurred in 6 % of patients ; 5 % discontinued treatment due to an adverse event . Grade 3/4 laboratory abnormalities included neutropenia ( 22 % ) , lymphopenia ( 16 % ) , anemia ( 6 % ) , thrombocytopenia ( 4 % ) , and ALT/AST elevations ( 3 % each ) . CONCLUSIONS Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders . The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens The study objective was to compare the efficacy and safety of peginterferon lambda-1a combined with ribavirin/daclatasvir ( Lambda/RBV/DCV ) , versus peginterferon alfa-2a combined with ribavirin/telaprevir ( Alfa/RBV/TVR ) , in patients chronically infected with hepatitis C virus ( HCV ) , genotype 1b . This was a prospect i ve , r and omized , open-label , phase 3 study ( NCT01718158 ) in adults ( aged ≥18 years ) who were treatment naïve or prior relapsers to peginterferon alfa/ribavirin therapy . The primary endpoint was sustained virologic response at post-treatment follow-up week 12 ( SVR12 ) . Patients were r and omized in a 2:1 ratio to receive 24 weeks of Lambda/RBV/DCV or response-guided 24 or 48 weeks of Alfa/RBV/TVR . Overall , 440 patients were treated ( 294 with Lambda/RBV/DCV ; 146 with Alfa/RBV/TVR ) . The proportion of patients achieving SVR12 was 88.8 % in the Lambda/RBV/DCV arm and 70.5 % in the Alfa/RBV/TVR arm ( difference between arms : 18.3 % ; 95 % confidence interval : 9.9 - 25.7 ; P < 0.0001 ) . Patients in the Lambda/RBV/DCV group had fewer rash-related adverse events ( AEs ) , cytopenic abnormalities , flu-like symptoms , serious AEs , and discontinuations due to AEs , but more liver abnormalities than those in the Alfa/RBV/TVR group . In conclusion , treatment with Lambda/RBV/DCV led to higher SVR12 rates and a more favorable safety profile than Alfa/RBV/TVR in patients with chronic HCV , genotype 1b infection The worldwide prevalence of chronic hepatitis C virus ( HCV ) infection is estimated to be approaching 200 million people . Current therapy relies upon a combination of pegylated interferon-α and ribavirin , a poorly tolerated regimen typically associated with less than 50 % sustained virological response rate in those infected with genotype 1 virus . The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B . Here we describe the profile of BMS-790052 , a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations ( EC50 ) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture . In a phase I clinical trial in patients chronically infected with HCV , administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log10 reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus . Genotypic analysis of sample s taken at baseline , 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system . These results provide the first clinical validation of an inhibitor of HCV NS5A , a protein with no known enzymatic function , as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors Objective To evaluate the safety and efficacy of daclatasvir , an HCV NS5A inhibitor with pangenotypic activity , administered with peginterferon-alfa-2a/ribavirin . Design In this Phase 2b double-blind , placebo-controlled study , treatment-naive adults with HCV genotype 1 ( N=365 ) or 4 ( N=30 ) infection were r and omly assigned ( 2:2:1 ) to daclatasvir 20 mg or 60 mg , or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin . Daclatasvir recipients achieving protocol -defined response ( PDR ; HCV-RNA < lower limit of quantitation at Week 4 and undetectable at Week 10 ) were rer and omised at Week 12 to continue daclatasvir/peginterferon-alfa-2a/ribavirin for 24 weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12 weeks . Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48 . Primary efficacy endpoints were undetectable HCV-RNA at Weeks 4 and 12 ( extended rapid virologic response , eRVR ) and at 24 weeks post-treatment ( sustained virologic response , SVR24 ) among genotype 1-infected patients . Results Overall , eRVR was achieved by 54.4 % ( 80/147 ) of genotype 1-infected patients receiving daclatasvir 20 mg , 54.1 % ( 79/146 ) receiving 60 mg versus 13.9 % ( 10/72 ) receiving placebo . SVR24 was achieved among 87 ( 59.2 % ) , 87 ( 59.6 % ) , and 27 ( 37.5 % ) patients in these groups , respectively . Higher proportions of genotype 4-infected patients receiving daclatasvir 20 mg ( 66.7 % ; 8/12 ) or 60 mg ( 100.0 % ; 12/12 ) achieved SVR24 versus placebo ( 50.0 % ; 3/6 ) . A majority of daclatasvir-treated patients achieved PDR and experienced less virologic failure and higher SVR24 rates with a shortened 24-week treatment duration . Adverse events occurred with similar frequency across all treatment groups . Conclusions The combination of daclatasvir/peginterferon-alfa/ribavirin was generally well tolerated and achieved higher SVR24 rates compared with placebo/peginterferon-alfa/ribavirin among patients infected with HCV genotype 1 or 4 . Trial registration number NCT01125189 BACKGROUND All-oral combination therapy is desirable for patients with chronic hepatitis C virus ( HCV ) infection . We evaluated daclatasvir ( an HCV NS5A replication complex inhibitor ) plus sofosbuvir ( a nucleotide analogue HCV NS5B polymerase inhibitor ) in patients infected with HCV genotype 1 , 2 , or 3 . METHODS In this open-label study , we initially r and omly assigned 44 previously untreated patients with HCV genotype 1 infection and 44 patients infected with HCV genotype 2 or 3 to daclatasvir  at a dose of 60 mg orally once daily plus sofosbuvir at a dose of 400 mg orally once daily , with or without ribavirin , for 24 weeks . The study was exp and ed to include 123 additional patients with genotype 1 infection who were r and omly assigned to daclatasvir plus sofosbuvir , with or without ribavirin , for 12 weeks ( 82 previously untreated patients ) or 24 weeks ( 41 patients who had previous virologic failure with telaprevir or boceprevir plus peginterferon alfa-ribavirin ) . The primary end point was a sustained virologic response ( an HCV RNA level of < 25 IU per milliliter ) at week 12 after the end of therapy . RESULTS Overall , 211 patients received treatment . Among patients with genotype 1 infection , 98 % of 126 previously untreated patients and 98 % of 41 patients who did not have a sustained virologic response with HCV protease inhibitors had a sustained virologic response at week 12 after the end of therapy . A total of 92 % of 26 patients with genotype 2 infection and 89 % of 18 patients with genotype 3 infection had a sustained virologic response at week 12 . High rates of sustained virologic response at week 12 were observed among patients with HCV subtypes 1a and 1b ( 98 % and 100 % , respectively ) and those with CC and non-CC IL28B genotypes ( 93 % and 98 % , respectively ) , as well as among patients who received ribavirin 
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Among all these regimens , DCV/SOF with or without RBV for 12 or 24 weeks was found to be an efficacious approach for treatment of different types of patients with infections with different HCV genotypes .
Conclusions Among the treatment regimens containing DCV , DCV/SOF has the highest SVR rate for the treatment of infection with different HCV genotypes in different patient context s ; thus , this regimen shows promise for the treatment of HCV infections