Anticipating a New Clinical Paradigm for Hepatitis C Virus Treatment

Overcoming Resistance

Appropriate therapy and patient management of chronic HCV infection can eradicate the virus with the current standard of care, pegylated interferon and ribavirin by achieving a sustained viral response (SVR).  Yet, less than 50% of patients with genotype 1, which is predominant in North America, achieve this objective. This has spurred research into more effective antiviral therapies that target specific steps in the virus life cycle. Similar to resistance observed with any targeted antiviral therapy, new targeted therapies for HCV infections have resulted in the selection of resistant viruses. Consequences include breakthrough or relapse if drugs are inappropriately prescribed or if patients fail to adhere to medication schedules. Thus, it is extremely important for treating physicians and patients to have a clear understanding of anti-viral resistance, its probable causes, consequences, and how it can be avoided during treatment. 

Although new antiviral therapies will shorten the course of treatment and increase efficacy, they present unfamiliar clinical challenges related to dosing, drug-drug interactions, and differing pharmacokinetic (PK) profiles. The intent of the round-table is to bring virologists, pharmacologists, patient advocates, experienced physicians, and patients together to initiate dialogue on educational issues in HCV antiviral resistance. Some key discussion points include: i) HCV is curable (resistant virus can be eliminated). ii) Resistant variants to antiviral drugs pre-exist before treatment initiation. iii) Multiple factors are important in achieving SVR including pharmacologic barriers, barriers to resistance, tolerability and compliance. iv) SVR can be achieved by a variety of means including combination treatment, compounds with different mechanisms of action, improved PK, potency and tolerability.

At the completion of the session, participants will be knowledgeable about various aspects of viral resistance before and following initiation of therapy, the clinical consequences of virologic failure, and how viral resistance can be prevented.