Abstract
Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. Methods In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. Results After PI-failure, 121 patients (cirrhotic = 86.8%) were retreated following three different strategies: A) with ‘GRT-guided’ regimens (N = 18); B) with ‘AASLD/EASL recommended, not GRT-guided’ regimens (N = 72); C) with ‘not recommended, not GRT-guided’ regimens (N = 31). Overall SVR rate was 91%, but all 18 patients treated with ‘GRT-guided’ regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving ‘AASLD/EASL recommended, not GRT-guided’ regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a ‘not recommended, not GRT-guided regimen’ (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT. Conclusion Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation.
| Original language | English |
|---|---|
| Pages (from-to) | 777.e1-777.e4 |
| Journal | Clinical Microbiology and Infection |
| Volume | 23 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2017 |
Fingerprint
Keywords
- Cirrhosis
- Direct acting antivirals
- Genotypic resistance testing
- HCV failure
- HCV resistance
- NS5A-inhibitors
- Protease-inhibitors
- Retreatment
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
Cite this
Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life. / Cento, V.; Barbaliscia, S.; Lenci, I.; Ruggiero, T.; Magni, C. F.; Paolucci, S.; Babudieri, S.; Siciliano, M.; Pasquazzi, C.; Ciancio, A.; Perno, C. F.; Ceccherini-Silberstein, F.; Micheli, V.; Troshina, Y.; Biliotti, E.; Milana, M.; Melis, M.; Teti, E.; Lambiase, L.; Menzaghi, B.; Nicolini, L. A.; Marenco, S.; Di Maio, V. C.; Aragri, M.; Pecchioli, A.; Bertoli, A.; Sarrecchia, C.; Macera, M.; Coppola, N.; Puoti, M.; Romagnoli, D.; Pellicelli, A.; Bonora, S.; Novati, S.; Baldanti, F.; Ghisetti, V.; Andreoni, M.; Taliani, G.; Rizzardini, G.; Angelico, M.; on behalf of; the HCV retreatment team VIRONET-C study group.
In: Clinical Microbiology and Infection, Vol. 23, No. 10, 01.10.2017, p. 777.e1-777.e4.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life
AU - Cento, V.
AU - Barbaliscia, S.
AU - Lenci, I.
AU - Ruggiero, T.
AU - Magni, C. F.
AU - Paolucci, S.
AU - Babudieri, S.
AU - Siciliano, M.
AU - Pasquazzi, C.
AU - Ciancio, A.
AU - Perno, C. F.
AU - Ceccherini-Silberstein, F.
AU - Micheli, V.
AU - Troshina, Y.
AU - Biliotti, E.
AU - Milana, M.
AU - Melis, M.
AU - Teti, E.
AU - Lambiase, L.
AU - Menzaghi, B.
AU - Nicolini, L. A.
AU - Marenco, S.
AU - Di Maio, V. C.
AU - Aragri, M.
AU - Pecchioli, A.
AU - Bertoli, A.
AU - Sarrecchia, C.
AU - Macera, M.
AU - Coppola, N.
AU - Puoti, M.
AU - Romagnoli, D.
AU - Pellicelli, A.
AU - Bonora, S.
AU - Novati, S.
AU - Baldanti, F.
AU - Ghisetti, V.
AU - Andreoni, M.
AU - Taliani, G.
AU - Rizzardini, G.
AU - Angelico, M.
AU - on behalf of
AU - the HCV retreatment team VIRONET-C study group
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. Methods In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. Results After PI-failure, 121 patients (cirrhotic = 86.8%) were retreated following three different strategies: A) with ‘GRT-guided’ regimens (N = 18); B) with ‘AASLD/EASL recommended, not GRT-guided’ regimens (N = 72); C) with ‘not recommended, not GRT-guided’ regimens (N = 31). Overall SVR rate was 91%, but all 18 patients treated with ‘GRT-guided’ regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving ‘AASLD/EASL recommended, not GRT-guided’ regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a ‘not recommended, not GRT-guided regimen’ (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT. Conclusion Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation.
AB - Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. Methods In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. Results After PI-failure, 121 patients (cirrhotic = 86.8%) were retreated following three different strategies: A) with ‘GRT-guided’ regimens (N = 18); B) with ‘AASLD/EASL recommended, not GRT-guided’ regimens (N = 72); C) with ‘not recommended, not GRT-guided’ regimens (N = 31). Overall SVR rate was 91%, but all 18 patients treated with ‘GRT-guided’ regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving ‘AASLD/EASL recommended, not GRT-guided’ regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a ‘not recommended, not GRT-guided regimen’ (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT. Conclusion Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation.
KW - Cirrhosis
KW - Direct acting antivirals
KW - Genotypic resistance testing
KW - HCV failure
KW - HCV resistance
KW - NS5A-inhibitors
KW - Protease-inhibitors
KW - Retreatment
UR - http://www.scopus.com/inward/record.url?scp=85021174540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021174540&partnerID=8YFLogxK
U2 - 10.1016/j.cmi.2017.04.005
DO - 10.1016/j.cmi.2017.04.005
M3 - Article
AN - SCOPUS:85021174540
VL - 23
SP - 777.e1-777.e4
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
SN - 1198-743X
IS - 10
ER -