***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Study C210 was a Phase IIa , exploratory trial to assess the activity of telaprevir on hepatitis C virus ( HCV ) early viral kinetics in treatment-naïve patients infected with genotype 4 ( G4 ) HCV . Methods Patients were r and omized to receive peginterferon and ribavirin alone , telaprevir monotherapy ( T arm ) , or telaprevir in combination with peginterferon/ribavirin ( TPR arm ) for 15 days , followed by a 46- or 48-week st and ard treatment phase . The current analysis aim ed to characterize the genotype and phenotype of HCV G4 variants emerging during telaprevir treatment . Results Five of the 8 ( 62.5 % ) patients in the telaprevir ( T ) arm had viral breakthrough ( vBT ) during the investigational treatment phase ( between baseline and Day 15 ) , compared to no patients in the TPR arm . HCV G4 viral variants with a T54A/T mutation were detected in two of these patients , as well as two other patients with detectable HCV RNA at the end of telaprevir treatment . Emergence of the T54A/T mutation was associated with a 2- to 4-fold decreased susceptibility to telaprevir . All patients with vBT during the investigational treatment phase or with a T54A/T mutation achieved undetectable HCV RNA 12 or 24 weeks after end of treatment with subsequent peginterferon/ribavirin treatment . Conclusions In this analysis in G4 HCV-infected patients , more patients in the telaprevir monotherapy arm experienced vBT with resistant variants compared to none with telaprevir combination therapy . The most commonly selected mutation T54A in telaprevir-treated G4 HCV patients was previously described in the context of G1 infection . Trial registration The trial was registered with Clinical Trials.gov ( NCT00580801 ) Vaniprevir is a competitive inhibitor of the hepatitis C virus ( HCV ) NS3/4A protease that has potent anti-HCV activity in pre clinical models . This placebo-controlled dose-ranging study assessed the safety , tolerability , and antiviral efficacy of vaniprevir monotherapy in patients with genotype 1 chronic HCV infection . Treatment-naive and treatment-experienced non-cirrhotic adult patients with baseline HCV RNA > 10(6)IU/ml were r and omized to receive placebo or vaniprevir at doses of 125 mg qd , 600 mg qd , 25 mg bid , 75 mg bid , 250 mg bid , 500 mg bid , and 700 mg bid for 8 days . Forty patients ( 82.5 % male , 75 % genotype 1a ) received at least one dose of placebo or vaniprevir . After 1 week of vaniprevir , the decrease in HCV RNA from baseline ranged from 1.8 to 4.6 log₁₀IU/ml across all treatment groups , and there was a greater than dose-proportional increase  in vaniprevir exposure at doses above 75 mg bid . The most commonly reported drug-related adverse events ( AEs ) were diarrhea ( n=5 ) and nausea ( n=5 ) . No pattern of laboratory or ECG abnormalities was observed , all AEs resolved during the study , and there were no discontinuations due to AEs . No serious AEs were reported . Resistance-associated amino acid variants were identified at positions R155 and D168 in patients infected with genotype 1a virus . Vaniprevir monotherapy demonstrated potent antiviral activity in patients with chronic genotype 1 HCV infection , and was generally well tolerated with no serious AEs or discontinuations due to AEs . Further development of vaniprevir , including studies in combination with other anti-HCV agents , is ongoing 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 Faldaprevir ( BI 201335 ) and deleobuvir ( BI 207127 ) are direct-acting antiviral agents under development for the treatment of chronic HCV infection . This article describes the final results of the Phase Ib SOUND-C1 study that evaluated the interferon-free oral combination of faldaprevir , deleobuvir and ribavirin in 32 treatment-naive patients infected with HCV genotype 1 . METHODS Patients were r and omized to receive deleobuvir 400 mg ( n=15 ) or 600 mg ( n=17 ) three times daily  plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks . Interferon-free therapy was followed by response-guided faldaprevir plus pegylated interferon-α2a/ribavirin to week 24 or 48 . RESULTS At week 4 , 73 % ( 11/15 ) and 100 % ( 17/17 ) of patients in the deleobuvir 400 mg and 600 mg groups achieved HCV RNA<25 IU/ml , respectively . During interferon-free treatment , virological breakthrough was reported in one patient and re-increase of HCV RNA in one patient . Both patients were successfully treated with interferon-containing therapy . The rate of sustained virological response 24 weeks after completion of treatment was 73 % ( 11/15 ) in the deleobuvir 400 mg group and 94 % ( 16/17 ) in the 600 mg group . During faldaprevir plus pegylated interferon-α2a/ribavirin treatment , the most common adverse events were pruritus ( 38 % of patients ) , rash ( 31 % ) and asthenia ( 31 % ) ; these were severe in approximately 3 % of patients . CONCLUSIONS Potent antiviral activity and favourable safety of the treatment regimen were demonstrated . Furthermore , the results suggest that patients with breakthrough at week 4 may be rescued with an interferon-containing regimen . Clinical trials.gov number NCT01132313 BACKGROUND & AIMS MK-7009 ( vaniprevir ) is a non-covalent competitive inhibitor of the hepatitis C virus ( HCV ) NS3/4A protease . This report presents the primary analysis results ( safety and sustained viral response ) of a phase 2b study of MK-7009 given in combination with peginterferon ( PegIFN ) alfa2a 180 μg weekly and ribavirin ( RBV ) 1000 - 1200 mg/day , for 24 - 48 weeks to non-cirrhotic patients who have failed previous PegIFN and RBV treatment . METHODS We present results of a r and omized , placebo-controlled , double-blind study of MK-7009 administered for 24 - 48 weeks in combination with PegIFN and RBV in 4 regimens to at least 40 patients per arm . Stratification by prior response to PegIFN and RBV was as follows : null response , partial response , breakthrough and relapse . HCV RNA was determined by Roche Cobas Taqman with a lower limit of detection ( LLoD ) of 10 IU/ml and a lower limit of quantification ( LLoQ ) of 25 IU/ml . RESULTS SVR24 in patients on MK-7009+PegIFN and ribavirin ( P/R ) was statistically superior to placebo+P/R in all treatment groups ( p<0.001 ) . MK-7009 at 300 mg b.i.d . and 600 mg b.i.d . is generally well tolerated for use for up to 48 weeks of therapy . Patients in MK-7009 regimens had higher rates of gastrointestinal adverse events as compared to control ( mostly mild to moderate ) . There were no significant differences in rates of anemia and rash between the MK-7009 regimens and control . CONCLUSIONS In conclusion , patients treated with MK-7009 plus P/R experienced significant improvement in SVR compared to P/R control in a population of GT 1 experienced patients BACKGROUND Patients with genotype 1 hepatitis C virus ( HCV ) who do not have a sustained response to therapy with peginterferon alfa and ribavirin  have a low likelihood of success with retreatment . METHODS We r and omly assigned patients with HCV genotype 1 who had not had a sustained virologic response after peginterferon alfa-ribavirin therapy  to one of four treatment groups : 115 patients to the T12PR24 group , receiving  telaprevir  ( 1125-mg loading dose , then 750 mg every 8 hours ) for 12 weeks and peginterferon alfa-2a ( 180 microg per week ) and ribavirin ( 1000 or 1200 mg per day , according to body weight ) for 24 weeks ; 113 patients to the T24PR48 group , receiving telaprevir for 24 weeks and peginterferon alfa-2a and ribavirin for 48 weeks ( at the same doses as in the T12PR24 group ) ; 111 patients to the T24P24 group , receiving telaprevir and peginterferon alfa-2a  for 24 weeks ( at the same doses as in the T12PR24 group ) ; and 114 patients to the PR48 ( or control ) group , receiving peginterferon alfa-2a and ribavirin for 48 weeks ( at the same doses as in the T12PR24 group ) . The primary end point was sustained virologic response ( undetectable HCV RNA levels 24 weeks after the last dose of study drugs ) . RESULTS The rates of sustained virologic response in the three telaprevir groups--51 % in the T12PR24 group , 53 % in the T24PR48 group , and 24 % in the T24P24 group -- were significantly higher than the rate in the control group ( 14 % ; P<0.001 , P<0.001 , and P=0.02 , respectively ) . Response rates were higher among patients who had previously had relapses than among nonresponders . One of the most common adverse events in the telaprevir groups was rash ( overall , occurring in 51 % of patients , with severe rash in 5 % ) . Discontinuation of study drugs because of adverse events was more frequent in the telaprevir groups than in the control group ( 15 % vs. 4 % ) . CONCLUSIONS In HCV-infected patients in whom initial peginterferon alfa and ribavirin treatment failed , retreatment with telaprevir in combination with peginterferon alfa-2a and ribavirin was more effective than retreatment with peginterferon alfa-2a and ribavirin alone . ( Clinical Trials.gov number , NCT00420784 . A r and om-primed complementary DNA library was constructed from plasma containing the uncharacterized non-A , non-B hepatitis ( NANBH ) agent and screened with serum from a patient diagnosed with NANBH . A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections . This clone is not derived from host DNA but from an 
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The evidence for our main outcomes of interest come from short-term trials , and we are unable to determine the effect of long-term treatment with DAAs .
The rates of hepatitis C morbidity and mortality observed in the trials are relatively low and we are uncertain as to how DAAs affect this outcome .
Overall , there is very low quality evidence that DAAs on the market or under development do not influence serious adverse events .
There is insufficient evidence to judge if DAAs have beneficial or harmful effects on other clinical outcomes for chronic HCV .
Simeprevir may have beneficial effects on risk of serious adverse event .
In all remaining analyses , we could neither confirm nor reject that DAAs had any clinical effects .
DAAs may reduce the number of people with detectable virus in their blood , but we do not have sufficient evidence from r and omised trials that enables us to underst and how SVR affects long-term clinical outcomes .