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 aimed to evaluate the safety and efficacy of this regimen in clinical practice settings 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 prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. 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 prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811.

Original languageEnglish
Pages (from-to)419-429
Number of pages11
Issue number2
StatePublished - 1 Feb 2016


FundersFunder number
Glaxo-Smith Kline
National Institutes of HealthP30CA016086, K24 DK066144, K24DA034621
National Institutes of Health
National Institute on Drug AbuseR01DA016065
National Institute on Drug Abuse
Boehringer Ingelheim
Bristol-Myers Squibb
Gilead SciencesUF UL1TR000064, 1UL1TR001111
Gilead Sciences
University of Florida
University of North Carolina Wilmington
Janssen Pharmaceuticals


    • Chronic Hepatitis
    • Direct-Acting Agent
    • NS3/4A Protease Inhibitor
    • NS5B


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