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INTRODUCTION

The introduction of direct-acting antiviral agents (DAAs) has revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection. Prior to the availability of DAAs, interferon (IFN)-based treatment regimens were limited by substantial side-effects, poor quality of life, and high rates of treatment failure.¹ By comparison, the newer IFN-free regimens are less complex, better tolerated, and require shorter treatment durations. Furthermore, patients with HCV infection can truly be considered “cured” as a result of modern antiviral therapy. In the clinical trial setting, many DAA-based combination regimens are reaching, or even achieving, 100% “cure” rates, which are measured as sustained virologic response (SVR) after 12 weeks of therapy. Furthermore, in real-world studies, patients are achieving very high SVR rates in routine clinical practice.

The choice of first-line antiviral therapy depends on factors such as HCV genotype, the presence and extent of liver disease, treatment history, and patient preferences.² In the post-IFN era, HCV genotype 3 infection remains particularly challenging to cure. Compared with other HCV genotypes, HCV genotype 3 is associated with faster liver disease progression and a higher risk of cirrhosis and hepatocellular carcinoma (HCC).³ Although the first-generation DAAs showed strong antiviral activity against HCV genotype 1, these agents had limited efficacy in the treatment of other HCV genotypes. However, the introduction of second-generation DAAs has expanded treatment options for patients with other HCV genotypes, including genotypes 1 through 6. The development of pan-genotypic HCV protease inhibitors has further expanded treatment options for all patients with HCV infection, regardless of HCV genotype.

Several practical considerations can ease the transition of HCV care into the IFN-free era. The use of multi-DAA combination regimens has increased the potential for interactions with other medications used by patients with chronic HCV infection.² Therefore, baseline screening for drug-drug interactions is particularly important for patients starting antiviral therapy.² Once the safety of the treatment regimen is verified, patients should be educated on the proper administration of treatment, including²:

• Medication dose
• Frequency of administration
• Whether medication should be taken with or without food
• Duration of therapy
• What to do in the event of missed doses
• Potential side-effects of therapy

Patient education regarding treatment adherence is also an essential component of HCV care. Poor adherence to DAA-based antiviral therapy is associated with reduced SVR rates, the enrichment of resistance-associated variants (RAVs), and reduced options for retreatment. Additional interventions may be needed to address patient-related risk factors for reduced adherence, including substance use, depression, neurocognitive disorders, and lack of social support.⁴ More complex treatment regimens, including lengthy treatment duration and higher pill burden, also increase the risk for poor adherence to antiviral therapy.⁵ In the context of treatment failure, the choice of second-line therapy also relies on factors such as likelihood of response, viral resistance, medication adherence, and tolerability.⁴ By ensuring the safety and efficacy of antiviral treatment regimens at each stage of care, pharmacists play a key role in improving clinical outcomes for patients with chronic HCV infection.

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