Only 12 of 3004 patients treated with ledipasvir-sofosbuvir for chronic hepatitis C virus (HCV) infection had detectable HCV RNA 12 weeks after the end of treatment, with approximately half experiencing reinfection, according to a study published in Clinical Infectious Diseases.1

The researchers evaluated the prevalence of late recurrent viremia, defined as sustained virologic response 12 weeks after the end of treatment but detectable HCV RNA at 24 weeks, across 11 phase 3 trials of ledipasvir-sofosbuvir.

The pangenotypic NS5B HCV inhibitor sofosbuvir in combination with ledispavir is effective in patients infected with HCV genotypes 1, 4, 5, and 6. Sofosbuvir in combination with ribavirin — with or without pegylated interferon — is effective in HCV genotype 2-3. HCV NS5A is a viral phosphoprotein that plays an important role in viral replication, assembly, and secretion.


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Eleven of those 12 patients had the same HCV genotype/subtype at baseline and at recurrence. Seven of 12 patients (58%) achieved HCV eradication with ledipasvir-sofosbuvir treatment according to phylogenetic analysis but became reinfected with a different HCV strain after treatment; the researchers did not indicate this as virologic relapse.

“This finding may have implications for selection of optimal retreatment strategies since reinfection is potentially simpler to treat due to the lack of exposure of the current viral quasispecies to therapy, whereas virologic relapse cases may have selected viral variants with reduced susceptibility,” wrote Christoph Sarrazin, MD, professor of medicine at JW Goethe University Hospital in Frankfurt, Germany, and colleagues. “Moreover, this finding also has implication for how long and what it takes to eliminate HCV and emphasizes the need to extend the continuum of HCV care beyond the SVR12 time point in persons at risk for reinfection.”

The remaining 5 patients had virologic relapse of the HCV strain that was present at baseline but that persisted in the liver and reemerged 24 weeks after treatment. These patients all had genotype 3a infections before treatment and at late relapse, which researchers said was consistent with the higher overall relapse rate for this strain. Deep sequencing analysis did not detect any known drug resistance-associated variants.

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Reference

  1. Sarrazin C, Isakov V, Svarovskaia ES, et al. Late relapse versus hepatitis C virus reinfection in patients with sustained virologic response after sofosbuvir-based therapies. Clin Infect Dis. 2016 Oct 12. doi: 10.1093/cid/ciw676