Ledipasvir/sofosbuvir plus ribavirin as highly effective regimen for recombinant strain RF1-2K/1B patients within georgian national hepatitis C elimination program

Background: Hepatitis C virus (HCV) recombinant strain RF1-2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 if only structural region is studied. We aimed to evaluate impact of RF1-2k/1b strain on Direct Acting Anti-viral (DAA) treatment outcomes within Georgian national hepatitis C elimination program. Methods: Study included 167 patients with HCV genotype 2 as determined by 5 untranslated region/Core (5'UTR/Core) genotyping assay. In addition to standard genotyping non-structural 5B (NS5B) region was sequenced and genotyping results compared. Study patients were treated within national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon/sofosbuvir/ribavirin (IFN/SOF/RBV) or ledipasvir/sofosbuvir/ribavirin (LDV/SOF/RBV) regimens respectively. Results: Of 167 patients evaluated 129 had RF1- 2k/1b genotype, while remaining 38 were infected with either 2a, 2c or 2k subtypes. Overall, sustained virologic response (SVR) was achieved more in genotype 2 than RF1-2k/1b patients (97.3% vs. 80.6%, p=0.004). LDV/SOF/RBV for 12 weeks was highly effective among both genotype 2 and RF1- 2k/1b (100.0 % and 97.9%, p=0.99) patients. Among 129 RF1-2k/1b patients SVR rate among LDV/SOF/RBV for 12 weeks was superior (97.9% SVR) to SOF/RBV for 12 (56.4%, p<0.0001) or 20 weeks (79.2%, p=0.01). IFN/SOF/RBV 12 week also demonstrated better response than SOF/RBV 12 weeks (88.9% vs. 56.4%, p=0.02) in these patients. Conclusions: High prevalence of RF1-2k/1b strain can significantly affect treatment outcomes. In our study, IFN/SOF/RBV and especially LDV/SOF/RBV found to have significantly higher SVR in patients infected with RF1-2k/1b strain as compared to standard HCV genotype 2 treatment with SOF/RBV 12 or 20 weeks. There is need for reassessing existing modalities for the management of HCV genotype 2 infections, especially in areas with high prevalence of RF1-2k/1b strain.