Evaluation of SVR4 and Treatment Completion as Indicators of Hepatitis C Cure in PWID

Overview

In a community-based cohort of people who inject drugs (PWID) treated for hepatitis C virus (HCV) infection, HCV RNA testing at treatment completion and at 4 weeks post-treatment (SVR4) showed high predictive value for sustained virologic response at 12 weeks post-treatment (SVR12). Positive predictive values were 96.6% for treatment completion and 100% for SVR4, supporting their use as alternative cure indicators.

Background

Hepatitis C virus can be cured in over 95% of patients completing direct-acting antiviral (DAA) therapy, with cure traditionally confirmed by undetectable HCV RNA at 12 weeks post-treatment (SVR12). Recent clinical guidance includes SVR4 as an alternative cure measure for select patients without cirrhosis or prior DAA exposure, motivated by high loss to follow-up before SVR12 and strong concordance between SVR4 and SVR12 in clinical trials. However, people who inject drugs (PWID), a population disproportionately affected by HCV, are underrepresented in trials and face unique barriers to care, necessitating evaluation of SVR4 and treatment completion RNA testing in this group.

Data Highlights

Key Findings

• Among 69 PWID completing HCV treatment, 84% achieved SVR12, confirming cure.
• Positive predictive value (PPV) of undetectable HCV RNA at treatment completion for SVR12 was 96.6%.
• PPV of undetectable HCV RNA at SVR4 for SVR12 was 100%, indicating perfect concordance in this sample.
• Negative predictive values (NPV) for both treatment completion and SVR4 were 100%, indicating detectable RNA at these earlier points predicted detectable RNA at SVR12.
• Three participants with detected RNA at SVR12 had the same genotype as pretreatment, suggesting treatment failure; two had different genotypes, suggesting reinfection.
• Findings support the use of SVR4 and treatment completion RNA testing as reliable early indicators of cure in PWID treated in community settings.

Clinical Implications

HCV RNA testing at treatment completion or at 4 weeks post-treatment can serve as practical alternative endpoints to SVR12 for confirming cure in PWID, a population with high loss to follow-up. Utilizing these earlier time points may facilitate timely clinical decision-making and reduce barriers to care in community-based treatment programs. Clinicians should consider patient-specific factors such as cirrhosis status and prior DAA exposure when applying these alternative endpoints.

Conclusion

This study demonstrates high concordance between HCV RNA results at treatment completion and SVR4 with the standard SVR12 endpoint among PWID, supporting updated clinical guidance to use earlier RNA testing as valid indicators of hepatitis C cure in this population.

References

1. NOW Study (NCT03987503) -- Accelerated test-and-treat protocol in community settings
2. FDA Guidance -- Approval of SVR12 as endpoint for HCV DAA therapies
3. Recent Clinical Guidance Update -- Inclusion of SVR4 as alternative cure measure
4. Randomized Clinical Trials and Drug Development Programs -- Concordance of SVR4 and SVR12