Ribavirin

Ribavirin is a broad-spectrum antiviral medication used in combination regimens. Marketed under the brand names Copegus, Rebetol, and Virazole, it is a synthetic nucleoside analog with activity against both RNA and DNA viruses.

It is approved for chronic hepatitis C virus (HCV) infection—typically in combination with peginterferon alpha or other direct-acting antivirals—as well as for severe respiratory syncytial virus (RSV) infections in infants. Ribavirin works by mimicking guanosine, inducing lethal mutagenesis in viral RNA and inhibiting viral RNA polymerase activity.

Response to ribavirin-based hepatitis C treatment is influenced by genetic variation in the IFNL3 gene (formerly known as IL28B). IFNL3 encodes interferon lambda-3, a cytokine that activates antiviral pathways and boosts the immune response against HCV.

Different IFNL3 genotypes affect how strongly a patient’s immune system responds to peginterferon alpha combined with ribavirin. Favorable genotypes lead to higher expression of interferon-stimulated genes and better viral clearance, while unfavorable genotypes result in a weaker response.

Genetic variation in IFNL3 stratifies patients into groups with distinct probabilities of achieving a sustained virologic response. Those with favorable genotypes generally respond well to standard ribavirin regimens, whereas patients with unfavorable genotypes have lower response rates and may require alternative therapies or treatment durations.

Favorable Response Genotype

• Effect: Standard ribavirin response with normal antiviral activity
• Clinical consequence: Higher likelihood of sustained virologic response (~70% after 48 weeks)
• Side effects: Typical ribavirin-related effects such as hemolytic anemia and fatigue; moderate severity and commonly observed

Unfavorable Response Genotype

• Effect: Reduced antiviral efficacy with standard regimens
• Clinical consequence: Lower chance of sustained virologic response (~30% after 48 weeks)
• Side effects: Similar safety profile—anemia, headache, nausea; moderate severity

Indeterminate/Not Available

• Effect: Unknown
• Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring

IFNL3 Genotype-Based Dosing

Examples of alternative treatments include interferon-free, direct-acting antiviral regimens such as sofosbuvir/ledipasvir or sofosbuvir/velpatasvir. These therapies have demonstrated high cure rates and may be preferred for patients with unfavorable IFNL3 genotypes.

• CPIC – Guideline for PEG-IFN-alpha-based Regimens and IFNL3