***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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    Input: The optimal retreatment strategy for patients chronically infected with hepatitis C virus who experience virologic failure after treatment with direct‐acting antiviral – based therapies remains unclear . In this multicenter , open‐label , phase 2 study , we evaluated the efficacy and safety of a fixed‐dose combination of sofosbuvir‐velpatasvir ( 400 mg/100 mg ) plus weight‐adjusted ribavirin administered for 24 weeks in patients who did not achieve sustained virologic response after prior treatment with direct‐acting antiviral regimens that included the nucleotide analogue nonstructural protein 5B inhibitor sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or without the nonstructural protein 3/4A protease inhibitor voxilaprevir . The primary efficacy endpoint was the proportion of patients achieving sustained virologic response at 12 weeks after the cessation of treatment . In total , 63 of 69 ( 91 % ; 95 % confidence interval , 82%‐97 % ) patients achieved sustained virologic response at 12 weeks , including 36 of 37 ( 97 % ; 95 % confidence interval , 86%‐100 % ) patients with hepatitis C virus genotype 1 infection , 13 of 14 ( 93 % ; 95 % confidence interval , 66%‐100 % ) patients with genotype 2 infection , and 14 of 18 ( 78 % ; 95 % confidence interval , 52%‐94 % ) patients with genotype 3 infection . Most adverse events were of mild or moderate severity . The most frequently reported adverse events were fatigue , nausea , headache , insomnia , and rash . One patient ( 1 % ) with genotype 1a infection discontinued all study drugs due to an adverse event ( irritability ) . Conclusion : Retreatment of patients who previously failed direct‐acting antiviral – based therapies  with sofosbuvir‐velpatasvir plus ribavirin for 24 weeks was well tolerated and effective , particularly those with hepatitis C virus genotype 1 or 2 infection . ( Hepatology 2017;66:1083‐1089 ) BACKGROUND Sofosbuvir-containing regimens have been approved for treatment of hepatitis C virus ( HCV ) infection in human immunodeficiency virus (HIV)-infected patients . We assessed the effect of treatment with sofosbuvir and ribavirin on patient-reported outcomes ( PROs ) in individuals with HIV/HCV coinfection . METHODS HIV/HCV-coinfected patients were treated for 12 or 24 weeks with sofosbuvir and ribavirin .  Matched HCV-monoinfected controls were also evaluated . All subjects completed st and ard PRO question naires before , during , and after treatment . RESULTS Included were 497 participants from the PHOTON-1 and PHOTON-2 clinical trials . At baseline , more impairment in PRO scores was noted in HIV/HCV-coinfected patients , compared with HCV-monoinfected patients . During treatment , moderate decrements in PRO scores ( change , up to -6.8 % on a 0%-100 % scale ; P = .0053 ) were experienced regardless of treatment duration and were similar to those for HCV-monoinfected patients ( all P > .05 ) . In 413 HIV/HCV-coinfected patients with a virologic response sustained for 12 weeks after treatment cessation , most PRO scores improved ( change , up to + 7.6 % ; P < .0001 ) , similar to findings for HCV-monoinfected patients . In multivariate analysis , in addition to clinico-demographic predictors , coinfection with HIV was associated with PRO impairment at baseline ( beta , up to -7.6 % ; P < .002 ) but not with treatment-emergent changes in PRO scores ( all P > .05 ) . CONCLUSIONS Patients with HIV/HCV coinfection tolerate interferon-free sofosbuvir-based anti-HCV regimens well and , despite the presence of some baseline impairment , have treatment-emergent changes in PRO scores that are similar to those of patients with HCV monoinfection . CLINICAL TRIALS REGISTRATION NCT01667731 ( PHOTON-1 ) , NCT01783678 ( PHOTON-2 ) , NCT01604850 ( FUSION ) , and NCT01682720 ( VALENCE ) BACKGROUND & AIMS We performed a phase 2 trial of the efficacy and safety of 4 , 6 , and 8 weeks of sofosbuvir , given in combination with the NS5A inhibitor velpatasvir and the NS3/4A protease inhibitor GS-9857 , in patients with hepatitis C virus ( HCV ) infection . METHODS We enrolled 161 treatment-naïve or previously treated patients infected with HCV genotypes 1 or 3 with or without compensated cirrhosis at 2 centers in New Zeal and , from September 2014 through March 2015 . All patients received sofosbuvir ( 400 mg ) and velpatasvir ( 100 mg ) plus GS-9857 ( 100 mg ) once daily . The primary efficacy end point was sustained virologic response at 12 weeks after therapy ( SVR12 ) . The duration of therapy was determined by baseline patient characteristics : 4 or 6 weeks for treatment-naïve patients without cirrhosis , 6 weeks for treatment-naïve patients with cirrhosis , and 6 or 8 weeks for treatment-experienced patients with or without cirrhosis . RESULTS Four weeks of sofosbuvir , velpatasvir , and GS-9857  produced an SVR12 in 4 of 15 ( 27 % ) treatment-naïve patients with HCV genotype 1 without cirrhosis . Six weeks of this combination produced a SVR12 in 14 of 15 ( 93 % ) treatment-naïve patients with HCV genotype 1 without cirrhosis , in 13 of 15 ( 87 % ) treatment-naïve genotype 1 patients with cirrhosis , in 15 of 18 ( 83 % ) treatment-naïve patients with HCV genotype 3 with cirrhosis , and in 20 of 30 ( 67 % ) patients with HCV genotype 1 who had failed an all-oral regimen of 2 or more direct-acting antiviral agents . Eight weeks of the drug combination produced an SVR12 in 17 of 17 ( 100 % ) patients with HCV genotype 1 , in 19 of 19 ( 100 % ) patients with HCV genotype 3 and cirrhosis who had failed pegylated interferon plus ribavirin , in 25 of 28 ( 89 % ) patients with HCV genotype 1 who had failed protease inhibitor-based triple therapy , and in 4 of 4 ( 100 % ) patients with HCV genotype 3 who had failed an all-oral regimen of ≥2 direct-acting antiviral agents . The most common reported adverse events were headache , nausea , and fatigue . CONCLUSIONS Eight weeks of treatment with the combination of sofosbuvir , velpatasvir , and GS-9857  produced an SVR12 in most treatment-naïve or previously treated patients with HCV genotype 1 or 3 infections , including those with compensated cirrhosis . Clinical Trials.gov , Number : NCT02202980 Although direct‐acting antiviral ( DAA ) therapies for chronic hepatitis C virus ( HCV ) infection have demonstrated high rates of sustained virologic response , virologic failure may still occur , potentially leading to the emergence of viral resistance , which can decrease the effectiveness of subsequent treatment . Treatment options for patients who failed previous DAA‐containing regimens , particularly those with nonstructural protein 5A inhibitors , are limited and remain an area of unmet medical need . This phase 2 , open‐label study ( MAGELLAN‐1 ) evaluated the efficacy and safety of glecaprevir ( GLE ) + pibrentasvir ( PIB ) ± ribavirin ( RBV ) in HCV genotype 1–infected patients with prior virologic failure to HCV DAA‐containing therapy . A total of 50 patients without cirrhosis were r and omized to three arms : 200 mg GLE + 80 mg PIB ( arm A ) , 300 mg GLE + 120 mg PIB with 800 mg once‐daily RBV ( arm B ) , or 300 mg GLE + 120 mg PIB without RBV ( arm C ) . By intent‐to‐treat analysis , sustained virologic response at posttreatment week 12 was achieved in 100 % ( 6/6 , 95 % confidence interval 61‐100 ) , 95 % ( 21/22 , 95 % confidence interval 78‐99 ) , and 86 % ( 19/22 , 95 % confidence interval 67‐95 ) of patients in arms A , B , and C , respectively . Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C ( two patients were lost to follow‐up in arm C ) . The majority of adverse events were mild in severity ; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase , total bilirubin , or hemoglobin were observed . Conclusion : The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA‐containing therapy ;  RBV coadministration did not improve efficacy . ( Hepatology 2017;66:389–397 ) BACKGROUND & AIMS Although hepatitis C virus ( HCV ) infection is common in patients with end-stage renal disease , highly efficacious , well-tolerated , direct-acting antiviral regimens have not been extensively studied in this population . We investigated the safety and efficacy of ombitasvir co-formulated with paritaprevir and ritonavir , administered with dasabuvir ( with or without ribavirin ) in a prospect i ve study of patients with stage 4 or 5 chronic kidney disease ( CKD ) . METHODS We performed a single-arm , multicenter study of treatment-naïve adults with HCV genotype 1 infection , without cirrhosis and with CKD stage 4 ( estimated glomerular filtration rate , 15 - 30 mL/min/1.73 m(2 ) ) or stage 5 ( estimated glomerular filtration rate , < 15 mL/min/1.73 m(2 ) or requiring hemodialysis ) . Twenty patients were given  ombitasvir co-formulated with paritaprevir and ritonavir , administered with dasabuvir for 12 weeks . Patients with HCV genotype 1a infections also received ribavirin ( n = 13 ) , whereas those with genotype 1b infection did not ( n = 7 ) . The primary end point was sustained virologic response ( serum HCV RNA < 25 IU/mL ) 12 weeks after treatment ended ( SVR12 ) . We collected data on on-treatment adverse events ( AEs ) , serious AEs , and laboratory abnormalities . RESULTS All 20 patients completed 12 weeks of treatment . Eighteen of the 20 patients achieved SVR12 ( 90 % ; 95 % confidence interval : 69.9 - 97.2 ) . One patient death after the end of the treatment ( unrelated to the treatment ) and 1 relapse accounted for the 2 non-SVRs . Adverse events were primarily mild or moderate , and no patient discontinued treatment due to an AE . Four patients experienced serious AEs ; all were considered unrelated to treatment . Ribavirin therapy was interrupted in 9 patients due to anemia ; 4 received erythropoietin . No blood transfusions were performed . CONCLUSIONS In a clinical trial , the combination of ombitasvir , paritaprevir , and ritonavir , administered with dasabuvir , led to an SVR12 in 90 % of patients with HCV genotype 1 infection and stage 4 or 5 CKD . The regimen is well tolerated , though RBV use may require a reduction or interruption to manage anemia . Clinical Trials.gov ID NCT02207088 BACKGROUND Patients chronically infected with hepatitis C virus ( HCV ) genotype 2 or 3 for whom treatment with peginterferon is not an option , or who have not had a response to prior interferon treatment , currently have no approved treatment options . In phase 2 trials , regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection . METHODS We conducted two r and omized , phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection . In one trial , patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin  ( 207 patients ) or matching placebo ( 71 ) for 12 weeks . In a second trial , patients who had not had a response to prior interferon therapy received sofosbuvir and ribav 
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Results Of the all-oral regimens , the efficacy ( SVR12 ≥ 90 % ) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines .
Conclusions On the basis of SVR12 , we established that for treating GT3 infections ( i ) regimens incorporating newer DAAs are more effective than those comprising older DAAs , and ( ii ) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens .
The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection