Safety of small molecules in combination with interferon-based therapy for hepatitis C virus

Abstract

Importance of the field: HCV is a leading cause of liver disease in the US, where ∼ 3.4 million people are chronically infected. The standard of care (SOC) of pegylated IFN and ribavirin combination therapy has limited efficacy with ∼ 50% sustained viral response, and is associated with a considerable adverse event profile in many patients. New drugs that directly target the virus are in development, and promise more effective therapies for chronic HCV infection.Areas covered in this review: Patient sub-classes with poor prognosis with SOC are identified, as are their associated adverse event profiles. Novel drugs, known as specifically targeted antiviral therapy for HCV (STAT-C), are currently being evaluated in clinical trials in multidrug combinations. Emerging safety signals and strategies to identify and prevent viral resistance to STAT-C drugs are also addressed.What the reader will gain: How the multidrug combinations are being developed and tested, what their relative strengths and weakness are, and which patient groups will benefit the most.Take home message: The central questions to successful multidrug combination therapies including novel small molecules will be their composite safety and efficacy profiles. Carefully conducted clinical trials and timely updates will be needed for ongoing improvements in patient care.