***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 & AIMS The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus ( HCV ) genotype 1 infection based on the findings of a phase 2 trial . We aim ed to evaluate the safety and efficacy of this regimen in clinical practice setting s in North America . METHODS We collected demographic , clinical , and virologic data , as well as reports of adverse outcomes , from sequential participants in HCV-TARGET -- a prospect i ve observational cohort study of patients undergoing HCV treatment in routine clinical care setting s. From January through October 2014 , there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir ( treatment duration of up to 16 weeks ) ; 169 of these patients received ribavirin . Most patients were male ( 61 % ) , Caucasian ( 76 % ) , or black ( 13 % ) ; 59 % had cirrhosis . Most patients had failed prior treatment with peginterferon and ribavirin without ( 46 % ) or with telaprevir or boceprevir ( 12 % ) . The primary outcome was sustained virologic response ( SVR ) , defined as the level of HCV RNA below quantification at least 64 days after the end of treatment ( beginning of week 12 after treatment -- a 2-week window ) . Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias . RESULTS The overall SVR rate was 84 % ( 675 of 802 patients , 95 % confidence interval , 81%-87 % ) . Model-adjusted estimates indicate patients with cirrhosis , prior decompensation , and previous protease inhibitor treatments were less likely to achieve an SVR . The addition of ribavirin had no detectable effects on SVR . The most common adverse events were fatigue , headache , nausea , rash , and insomnia . Serious adverse events and treatment discontinuation occurred in only 5 % and 3 % of participants , respectively . CONCLUSIONS In a large prospect i ve observational cohort study , a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation . Clinical Trials.gov : NCT01474811 BACKGROUND & AIMS R and omised controlled trials ( RCTs ) show that triple therapy ( TT ) with peginterferon alfa , ribavirin , and boceprevir ( BOC ) or telaprevir ( TVR ) is more effective than peginterferon-ribavirin dual therapy ( DT ) in the treatment of genotype 1 ( G1 ) chronic hepatitis C ( CHC ) patients with previous relapse ( RR ) , partial response ( PAR ) , and null-response ( NR ) . We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC . METHODS The available published literature provided the data source . The target population was made up of previously treated Caucasian patients with G1 CHC and these were evaluated over a lifetime horizon by Markov model . The study was carried out from the perspective of the Italian National Health Service . Outcomes included discounted costs ( in euro at 2012 value ) , life years gained ( LYG ) , quality adjusted life year ( QALY ) , and incremental cost-effectiveness ratio (ICER).The robustness of the results was evaluated by one-way deterministic and multivariable probabilistic sensitivity analyses . RESULTS In RR patients , ICER per LYG compared to no therapy was € 9555 for BOC-LEAD-IN-RR and € 7910 for TVR-LEAD-IN-RR , being BOC dominated by TVR . In PAR patients , ICER for LYG was € 11,947 for BOC-LEAD-IN-PAR and € 14,931 for TVR-PAR , being TVR cost-effective compared to BOC ( ICER for QALY € 22,258 ) . In NR patients , ICER for LYG was € 26,499 for TVR-LEAD-IN-NR . The models were sensitive to likelihood of sustained virological response and to BOC/TVR prices . CONCLUSIONS 1st generation HCV PI is highly cost-effective compared to no therapy in RR and PAR G1 CHC patients . TVR dominated BOC in RR , and was cost-effective compared to BOC in PAR patients . In NR patients an assessment of the response after a lead-in period should be performed to improve safety and cost-effectiveness Background SPRINT-2 demonstrated that boceprevir ( BOC ) , an oral hepatitis C virus ( HCV ) nonstructural 3 ( NS3 ) protease inhibitor , added to peginterferon alfa-2b ( P ) and ribavirin ( R ) significantly increased sustained virologic response rates over PR alone in previously untreated adult patients with chronic HCV genotype 1 . We estimated the long-term impact of triple therapy vs. dual therapy on the clinical burden of HCV and performed a cost-effectiveness evaluation . Methods A Markov model was used to estimate the incidence of liver complications , discounted costs ( 2010 US$ ) , quality -adjusted life years ( QALYs ) , and incremental cost-effectiveness ratios ( ICERs ) of three treatment strategies for treatment-naïve patients with chronic HCV genotype 1 . The model simulates the treatment regimens studied in SPRINT-2 in which PR was administered for 4 weeks followed by : 1 ) placebo plus PR for 44 weeks ( PR48 ) ; 2 ) BOC plus PR using response guided therapy ( BOC/RGT ) ; and 3 ) BOC plus PR for 44 weeks ( BOC/PR48 ) and makes projections within and beyond the trial . HCV-related state-transition probabilities , costs , and utilities were obtained from previously published studies . All costs and QALYs were discounted at 3 % . Results The model projected approximately 38 % and 43 % relative reductions in the lifetime incidence of liver complications in the BOC/RGT and BOC/PR48 regimens compared with PR48 , respectively . Treatment with BOC/RGT is associated with an incremental cost of $ 10,348 and an increase of 0.62 QALYs compared to treatment with PR48 . Treatment with BOC/PR48 is associated with an incremental cost of $ 35,727 and an increase of 0.65 QALYs compared to treatment with PR48 . The ICERs were $ 16,792/QALY and $ 55,162/QALY for the boceprevir-based treatment groups compared with PR48 , respectively . The ICER for BOC/PR48 compared with BOC/RGT was $ 807,804 . Conclusion The boceprevir-based regimens used in the SPRINT-2 trial were projected to substantially reduce the lifetime incidence of liver complications and increase the QALYs in treatment-naive patients with hepatitis C genotype 1 . It was also demonstrated that boceprevir-based regimens offer patients the possibility of experiencing great clinical benefit with a shorter duration of therapy . Both boceprevir-based treatment strategies were projected to be cost-effective at a reasonable threshold in the US when compared to treatment with PR48 BACKGROUND Patients infected with chronic HCV genotype 1 experience liver complications as the disease progresses . This study aims to project the long-term reduction of liver complications and cost-effectiveness of treatment strategies , including co-administrating boceprevir ( BOC ) with pegylated interferon-α2b ( PEG-IFN ) and ribavirin compared with st and ard of care ( SOC ) of PEG-IFN and ribavirin only . METHODS A Markov model was created to estimate the expected costs and quality -adjusted life-years ( QALYs ) associated with treatment strategies outlined in the BOC package insert in Singapore . Patient characteristics were from pivotal trials , the transition probabilities and QALYs were estimated from publications , and the pharmaceutical and health status costs were obtained from a public hospital in Singapore . The threshold of cost-effectiveness was chosen as 65,000 SGD for this study . RESULTS For treatment-naive patients  , BOC is highly cost-effective compared with SOC ( 179 SGD/QALY ) and cost-saving for patients who have failed prior treatment , due to higher QALYs from better sustained virological response ( SVR ) and lower costs from avoidance of complications . Sub-group analyses show that BOC is cost-effective for non-cirrhotic treatment-experienced patients and null responders . It out-performs SOC for treatment-naive non-cirrhotic and cirrhotic patients who have failed prior treatment . Even after adjusting for higher prevalence of favourable IL28B genotype in Asians  , BOC is cost-effective compared with SOC . Only untreated cirrhotic patients showed inconclusive cost-effectiveness for BOC . CONCLUSIONS Compared with SOC , BOC prevents more HCV liver complications from HCV genotype 1 , particularly in patients who have failed previous SOC . Improved SVR and shortened duration of treatment result in BOC being potentially cost-saving or cost-effective in an Asian population In France , 190 306 patients were suffering from chronic hepatitis C in 2012 . These patients have a decreased life expectancy and are susceptible to complications associated with chronic hepatitis . Current treatments are poorly tolerated and their effectiveness varies depending on the genotype of the virus . Sofosbuvir , a new class of treatment , has demonstrated in five phase III trials sustained viral response ( SVR ) rates of over 90 % across genotypes , higher than current treatments and has a tolerance profile similar to placebo . The objective was to determine the cost-effectiveness of using sofosbuvir in the treatment of  chronic HCV infection .  A Markov model was used to compare treatment strategies with and without sofosbuvir . The model simulated the natural history of HCV infection . SVR rates were based on data from clinical trials . Utilities associated with different stages of disease were based on data from the literature . French direct medical costs were used . Price for  sofosbuvir was the price used in the early access program for severe fibrosis stages . The incremental cost – effectiveness ratio  for sofosbuvir versus current reference treatments was € 16 278/QALY and varied from 40 000 € /QALY for F0 stages to 12 080 € /QALY for F4 stages . The sensitivity analyses carried out confirmed the robustness of this result . Sofosbuvir is a cost-effective treatment option for patients with hepatitis Editors ' Notes Context Newly approved drug regimens for hepatitis C virus ( HCV ) treatment seem more efficacious and safer than older regimens but are expensive . Contribution In a cost-effectiveness analysis , combination therapy with sofosbuvir and ledipasvir reduced HCV-related complications and was cost-effective for most patients . However , its use would cost an additional $ 65 billion over the next 5 years while off setting only $ 16 billion of the overall cost of HCV care . Caution Not all data came from large r and omized trials . Implication If prices remain at current levels , government and private providers will need additional financial re sources or will need to prioritize patients for HCV treatment . More than 3 million persons are chronically infected with hepatitis C virus ( HCV ) in the United States , and most of them are undiagnosed ( 1 , 2 ) . Infection with HCV is the leading cause of hepatocellular carcinoma ( HCC ) and is the most common indication for liver transplantation ( 3 ) . In 2011 , the economic burden associated with chronic HCV infection in the United States was $ 6.5 billion ( 4 ) . The recent approval of 3 new drugssofosbuvir , a first-in-class , once-daily HCV RNA polymerase inhibitor ; simeprevir , a once-daily protease inhibitor ; and sofosbuvir plus ledipasvir , the first oral combination therapyby the U.S. Food and Drug Administration ( FDA ) marked the beginning of a new era for HCV treatment ( 57 ) . Until then , the old st and ard of care ( oSOC ) was based on peginterferon and ribavirin with or without boceprevir and telaprevir . With the advent of the new drugs , HCV treatment can for the first time be provided without interferon-based therapy , which is associated with considerable toxicity ( 8) . As a result , many patients who were unable to tolerate previous therapies are now eligible for HCV treatment . These agents are superior , with sustained virologic response ( SVR ) rates greater than 95 % in most patients and shorter duration of treatment and fewer adverse effects than the oSOC ( 9 , 10 ) . To guide clinicians , the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America jointly published a practice guideline with new recommendations for HCV treatment as a Web document with plans for ongoing up date s ( 11 ) . These recommendations include FDA -approved as well as off-label drug combinations of sofosbuvir and ledipasvir . Enthusiasm for the new drugs has been dampened by their cost : Sofosbuvir is currently priced at $ 1000 per day and sofosbuvirledipasvir at $ 1125 per day . The total cost of treatment can be as high as $ 150000 per patient . The high price of sofosbuvir has drawn criticism from patient advocates ( 12 ) , U.S. lawmakers ( 13 
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Marked heterogeneity in cost-effectiveness estimates was observed despite this stratification .
This analysis suggested that there are still circumstances where DAAs are not cost-effective .