***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 Interferon-based treatment is not suitable for many patients with hepatitis C virus ( HCV ) infection because of contraindications such as psychiatric illness , and a high burden of adverse events . We assessed the efficacy and safety of an interferon-free regimen -- a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir ( 400 mg ) and the HCV NS5A inhibitor ledipasvir ( 90 mg ) , with and without ribavirin -- in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen . METHODS For this open-label study , we enrolled 100 adult patients ( > 18 years ) with HCV infection at a centre in the USA between Nov 2 , 2012 , and Dec 21 , 2012 . In cohort A , we used a computer-generated sequence to r and omly assign ( 1:1:1 ; stratified by HCV genotype [ 1a vs 1b ] ) 60 non-cirrhotic , treatment-naive patients to receive sofosbuvir plus ledipasvir for 8 weeks ( group 1 ) , sofosbuvir plus ledipasvir and ribavirin for 8 weeks ( group 2 ) , or sofosbuvir plus ledipasvir for 12 weeks ( group 3 ) . In cohort B , we r and omly allocated ( 1:1 ; stratified by genotype and presence or absence of cirrhosis ) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive sofosbuvir plus ledipasvir for 12 weeks ( group 4 ) or sofosbuvir plus ledipasvir and ribavirin for 12 weeks ( group 5 ) . 22 ( 55 % ) of 40 patients in cohort B had compensated cirrhosis . The primary endpoint was sustained virological response 12 weeks after treatment ( SVR12 ) , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT01329978 . FINDINGS In cohort A , SVR12 was achieved by 19 ( 95 % ) of 20 patients ( 95 % CI 75 - 100 ) in group 1 , by 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 2 , and by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 3 . In cohort B , SVR12 was achieved by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 4 and by all 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 5 . Two patients had viral relapse ; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment . The most common adverse events were nausea , anaemia , upper respiratory tract infection , and headache . One patient in group five had a serious adverse event of anaemia , thought to be related to ribavirin treatment . INTERPRETATION These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV , irrespective of treatment history or the presence of compensated cirrhosis . Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin . FUNDING Gilead Sciences BACKGROUND Hepatitis C virus ( HCV ) genotype 4 accounts for about 13 % of global HCV infections . Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability , an unmet need exists for effective all-oral regimens . We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir , an NS5A inhibitor , and paritaprevir ( ABT-450 ) , an NS3/4A protease inhibitor dosed with ritonavir ( ombitasvir plus paritaprevir plus ritonavir ) , given with or without ribavirin . METHODS In this multicentre ongoing phase 2b , r and omised , open-label combination trial ( PEARL-I ) , patients were recruited from academic , public , and private hospitals and clinics in France , Hungary , Italy , Pol and , Romania , Spain , Turkey , and the USA . Eligible participants were aged 18 - 70 years with non-cirrhotic , chronic HCV genotype 4 infection ( documented ≥6 months before screening ) and plasma HCV RNA levels higher than 10,000 IU/mL. Previously untreated ( treatment-naive ) patients were r and omly assigned ( 1:1 ) by computer-generated r and omisation lists to receive once-daily ombitasvir ( 25 mg ) plus paritaprevir ( 150 mg ) plus ritonavir ( 100 mg ) with or without weight-based ribavirin for 12 weeks . Previously treated ( treatment-experienced ) patients who had received pegylated interferon plus ribavirin all received the ribavirin-containing regimen . The primary endpoint was a sustained virological response ( HCV RNA < 25 IU/mL ) 12 weeks after the end of treatment ( SVR12 ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT01685203 . FINDINGS Between Aug 14 , 2012 , and Nov 19 , 2013 , 467 patients with HCV infection were screened , of whom 174 were infected with genotype 4 . 135 patients were r and omly assigned to treatment and received at least one dose of study medication ; 86 patients were treatment-naive , of whom 44 received ombitasvir plus paritaprevir plus ritonavir and 42 received ombitasvir plus paritaprevir plus ritonavir with ribavirin , and 49 treatment-experienced patients received the ribavirin-containing regimen . In previously untreated patients , SVR12 rates were 100 % ( 42/42 [ 95 % CI 91·6 - 100 ] ) in the ribavirin-containing regimen and 90·9 % ( 40/44 [ 95 % CI 78·3 - 97·5 ] ) in the ribavirin-free regimen . No statistically significant differences in SVR12 rates were noted between the treatment-naive groups ( mean difference -9·16 % [ 95 % CI -19·61 to 1·29 ] ; p=0·086 ) . All treatment-experienced patients achieved SVR12 ( 49/49 ; 100 % [ 95 % CI 92·7 - 100 ] ) . In the ribavirin-free group , two ( 5 % ) of 42 treatment-naive patients had virological relapse , and one ( 2 % ) of 44 had virological breakthrough ; no virological failures were recorded in the ribavirin-containing regimen . The most common adverse event was headache ( 14 [ 29 % ] of 49 treatment-experienced patients and 14 [ 33 % ] of 42 treatment-naive patients ) . No adverse event-related discontinuations or dose interruptions of study medications , including ribavirin , were noted , and only four patients ( 4 % ) of 91 receiving ribavirin required dose modification for haemoglobin less than 100 g/L or anaemia . INTERPRETATION An interferon-free regimen of ombitasvir plus paritaprevir plus ritonavir with or without ribavirin achieved high sustained virological response rates at 12 weeks after the end of treatment and was generally well tolerated , with low rates of anaemia and treatment discontinuation in non-cirrhotic previously untreated and previously treated patients with HCV genotype 4 infection . FUNDING AbbVie 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 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 and those who did not ( 94 % and 98 % , respectively ) . The most common adverse events were fatigue , headache , and nausea . CONCLUSIONS Once-daily oral daclatasvir plus sofosbuvir was associated with high rates of sustained v 
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For the outcome incidence of AEs , few significant differences were observed , which were explained by the presence of RBV .
No significant differences were observed for serious AE outcomes .
Small differences were observed in any AEs , but not in serious AEs