Sofosubuvir, Simeprevir, +/- Ribavirin in HCV Protease Inhibitor-Experienced Patients

Background: Little data exists on use of HCV protease inhibitors (PIs) as part of a treatment (Rx) regimen for PI-experienced G1 patients (pts). Since polymorphisms associated with PI-resistance decrease to baseline levels over time in most studied subjects, sofosbuvir (SOF) + simeprevir (SMV) +/- ribavirin (RBV) represents a potential retreatment option for PI-experienced pts.

Methods: We compiled a retrospective cohort of HCV PI-experienced G1 pts treated with SOF+SMV+/-RBV at our center. Baseline factors including prior regimen & Rx response, fibrosis stage, HCV genotype & resistance testing (population-based) data, viral RNA levels, demographic data as well as on Rx response, SVR4, and SVR12 were collected and reported.

Results: In 2014, 15 pts with genotype 1 and prior PI experience initiated Rx because of clinical need with 12 wks SOF+SMV with (10) or without (5) RBV . Median age was 61 yrs (range 26-73), baseline HCV RNA 6.5 log IU/ml (5.5-7.0 log), 12 were male, and 10 had cirrhosis. PI Rx occurred 26 (5-85) months prior and included telaprevir (10), boceprevir (3), ABT 450/r (1), GS9451 (1) as part of Rx regimen with 11 nonresponders, 1 relapser, and 3 intolerant of Rx. All had genotype and resistance testing performed prior to SOF+SMV+/-RBV. Of the 9 G1a pts, Q80K was detected in 4, Q80L in1. Of the 6 G1b pts, V36I and T54S were detected in 1 pt each. No other mutations associated with PI resistance were detected.

Responses to SOF+SMV+/-RBV are shown in the table.

Conclusions: Conclusion: SOF+SMV+/-RBV treatment may be appropriate for carefully selected PI-experienced G1 pts including those with cirrhosis. Further study is needed to confirm these findings.

*The pt with relapse received SOF+SMV+RBV, had G1b, cirrhosis and a prior history of telaprevir-based Rx completed 14 months prior, and had no known mutations associated with resistance.