***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 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 RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and that is positive-str and ed with respect to the encoded NANBH antigen . These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae . This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents BACKGROUND In patients with chronic infection with hepatitis C virus ( HCV ) genotype 1 , treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50 % . Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment . METHODS A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were r and omly assigned to receive one of four treatments involving various combinations of telaprevir ( 1250 mg on day 1 , then 750 mg every 8 hours ) , peginterferon alfa-2a ( 180 microg weekly ) , and ribavirin ( dose according to body weight ) . The T12PR24 group ( 81 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks , followed by peginterferon alfa-2a and ribavirin for 12 more weeks . The T12PR12 group ( 82 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks . The T12P12 group ( 78 patients ) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks . The PR48 ( control ) group ( 82 patients ) received peginterferon alfa-2a and ribavirin for 48 weeks . The primary end point , a sustained virologic response ( an undetectable HCV RNA level 24 weeks after the end of therapy ) , was compared between the control group and the combined T12P12 and T12PR12 groups . RESULTS The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48 % ( 77 of 160 patients ) , as compared with 46 % ( 38 of 82 ) in the PR48 ( control ) group ( P=0.89 ) . The rate was 60 % ( 49 of 82 patients ) in the T12PR12 group ( P=0.12 for the comparison with the PR48 group ) , as compared with 36 % ( 28 of 78 patients ) in the T12P12 group ( P=0.003 ; P=0.20 for the comparison with the PR48 group ) . The rate was significantly higher in the T12PR24 group ( 69 % [ 56 of 81 patients ] ) than in the PR48 group ( P=0.004 ) . The adverse events with increased frequency in the telaprevir-based groups were pruritus , rash , and anemia . CONCLUSIONS In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously , one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with st and ard therapy . Response rates were lowest with the regimen that did not include ribavirin . ( Clinical Trials.gov number , NCT00372385 . IMPORTANCE The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different population s. OBJECTIVE To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics . DESIGN , SETTING , AND PATIENTS Single-center , r and omized , 2-part , open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus ( HCV ) genotype 1 enrolled at the National Institutes of Health ( October 2011-April 2012 ) . INTERVENTIONS In the study 's first part , 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks . In the second part , 50 participants with all stages of liver fibrosis were r and omized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks . MAIN OUTCOMES AND MEASURES The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion ( sustained virologic response of 24 weeks [ SVR24 ] ) . RESULTS In the first part of the study , 9 participants ( 90 % ; 95 % CI , 55%-100 % ) achieved SVR24 . In the second part , 7 participants ( 28 % ) in the weight-based group and 10 ( 40 % ) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68 % ( 95 % CI , 46%-85 % ) in the weight-based group and 48 % ( 95 % CI , 28%-69 % ; P = .20 ) in the low-dose group . Twenty individuals participated in a pharmacokinetic-viral kinetic sub study , which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR ( clearance , 3.57/d vs 5.60/d ; P = .009 ) . The most frequent adverse events were headache , anemia , fatigue , and nausea . There were 7 grade 3 events including anemia , neutropenia , nausea , hypophosphatemia , and cholelithiasis or pancreatitis . No one discontinued treatment due to adverse events . CONCLUSION AND RELEVANCE In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response , a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin result ed in SVR24 rates of 68 % and 48 % , respectively . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01441180 BACKGROUND Protease inhibitors have improved treatment of infection with hepatitis C virus ( HCV ) , but dosing , a low barrier to resistance , drug interactions , and side-effects restrict their use . We assessed the safety and efficacy of sofosbuvir , a uridine nucleotide analogue , in treatment-naive patients with genotype 1 - 3 HCV infection . METHODS In this two-cohort , phase 2 trial , we recruited treatment-naive patients with HCV genotypes 1 - 3 from 22 centres in the USA . All patients were recruited between Aug 16 , 2010 , and Dec 13 , 2010 , and were eligible for inclusion if they were aged 18 - 70 years , had an HCV RNA concentration of 50,000 IU/mL or greater , and had no cirrhosis . We r and omly allocated all eligible patients with HCV genotype 1 ( cohort A ) to receive sofosbuvir 200 mg , sofosbuvir 400 mg , or placebo ( 2:2:1 ) for 12 weeks in combination with peginterferon ( 180 μg per week ) and ribavirin ( 1000 - 1200 mg daily ) , after which they continued peginterferon and ribavirin for an additional 12 weeks or 36 weeks ( depending on viral response ) . R and omisation was done by use of a computer-generated r and omisation sequence and patients and investigators were masked to treatment allocation until week 12 . Patients with genotypes 2 or 3 ( cohort B ) received open-label sofosbuvir 400 mg plus peginterferon and ribavirin for 12 weeks . Our primary outcomes were safety and tolerability . Secondary efficacy analyses were by intention to treat and endpoints included sustained virological response , defined as undetectable HCV RNA at post-treatment weeks 12 and 24 . This study is registered with Clinical Trials.gov , number NCT01188772 . FINDINGS In cohort A , 122 patients were assigned 200 mg sofosbuvir ( 48 patients ) , 400 mg sofosbuvir ( 48 ) , or placebo ( 26 ) . We enrolled 25 patients into cohort B. The most common adverse events -- fatigue , headache , nausea , and chills -- were consistent with those associated with peginterferon and ribavirin . Eight patients discontinued treatment due to adverse events , two ( 4 % ) receiving sofosbuvir 200 mg , three ( 6 % ) receiving sofosbuvir 400 mg , and three ( 12 % ) receiving placebo . In cohort A , HCV RNA was undetectable at post-treatment week 12 in 43 ( 90 % ; 95 % CI 77 - 97 ) of 48 patients in the 200 mg sofosbuvir group ; 43 ( 91 % ; 80 - 98 ) of 47 patients in the 400 mg sofosbuvir group , and 15 ( 58 % ; 37 - 77 ) of 26 patients in the placebo group . In cohort B , 23 ( 92 % ) of 25 patients had undetectable HCV RNA at post-treatment week 12 . INTERPRETATION Our findings lend support to the further assessment , in phase 2 and 3 trials , of sofosbuvir 400 mg plus peginterferon and ribavirin for 12 weeks in treatment-naive patients with HCV genotype-1 . FUNDING Gilead Sciences All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus ( HCV ) infection , particularly those who are poor c 
    Output:
    
Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 ( SVR , 79%-86 % ) .
AND RELEVANCE New , short- duration , simpler therapies result in high SVR rates for HCV-infected patients .
In conjunction with increased screening for HCV as suggested by recent Centers for Disease Control and Prevention guidelines , availability of new therapies may lead to the treatment of many more people with chronic HCV infection