Is retreatment appropriate for a patient with hepatitis C (HCV) who has been previously treated and becomes reinfected?

Retreatment of Hepatitis C Reinfection

Yes, retreatment is absolutely appropriate for patients with hepatitis C who achieve sustained virologic response (SVR) and subsequently become reinfected. These patients should be treated according to the same guidelines as treatment-naïve patients, as reinfection represents a new infection rather than treatment failure 1.

Key Distinction: Reinfection vs. Relapse

Reinfection is a completely different clinical scenario from treatment failure or relapse:

• Reinfection occurs when a patient who achieved SVR (confirmed HCV RNA negative at 12-24 weeks post-treatment) acquires a new HCV infection through ongoing risk behaviors 1
• Relapse represents recurrence of the original viral strain, typically occurring within the first 24 weeks after treatment cessation 2
• Sequence analysis demonstrates that reinfection involves genetically distinct viral strains, while relapse shows nearly identical sequences to the original infection 2

Treatment Approach for Reinfected Patients

Patients with documented reinfection should be treated exactly as treatment-naïve patients, following current genotype-specific guidelines:

For Genotypes 1-6 Without Cirrhosis:

• 8 weeks of glecaprevir/pibrentasvir (300mg/120mg daily) is the recommended duration 3
• Alternative regimens include sofosbuvir/velpatasvir or sofosbuvir/ledipasvir for 12 weeks 1

For Genotypes 1-6 With Compensated Cirrhosis:

• 8 weeks of glecaprevir/pibrentasvir for treatment-naïve patients with cirrhosis 3
• Sofosbuvir/velpatasvir or sofosbuvir/ledipasvir for 12 weeks are alternatives 1

Monitoring and Prevention Strategies

High-risk patients require structured surveillance after achieving SVR:

• Annual HCV RNA testing should be performed in people who inject drugs (PWID) or men who have sex with men (MSM) with ongoing risk behaviors 1
• Patients with ongoing drug use should not be excluded from treatment based on perceived reinfection risk 1
• Reinfection rates in high-risk populations are relatively low at 1-5% per year 1

Risk reduction counseling is essential:

• The risk of reinfection should be explicitly explained to individuals with ongoing risk behaviors to positively modify behavior 1
• However, the concern for reinfection should never be used as justification to withhold treatment 1

Important Clinical Caveats

Do not confuse reinfection with treatment failure scenarios:

• Patients who fail DAA therapy (never achieved SVR) require different retreatment strategies based on prior drug exposure and resistance patterns 1
• Treatment failure patients may have resistance-associated substitutions (RAS) that affect retreatment choices, particularly with NS5A inhibitors 1, 4
• Reinfected patients who previously achieved SVR do not carry these resistance concerns from their prior infection 1

Expected outcomes are excellent:

• Reinfected patients respond to treatment similarly to treatment-naïve patients, with SVR rates of 95-99% using modern DAA regimens 1, 3
• There is no evidence that prior successful treatment diminishes response to retreatment for reinfection 1