Abstract
Background: The used first generation protease inhibitors may be hampered by virological failure in partially interferon-sensitive patients. Aim: To investigate early hepatitis C virus (HCV)-RNA decay and quasispecies modifications, and disclose viral dynamics underlying failure. Methods: Viraemia decay at early time-points during telaprevir treatment was modelled according to Neumann et al. (1998). NS3-sequences were obtained by population-sequencing and ultradeep-454-pyrosequencing. Results: 13 treatment-experienced (8 non-responders, 5 relapsers), and two cirrhotic naïve patients, received telaprevir. +. pegylated-interferon-α. +. ribavirin.Viraemia decay was biphasic. In all patients, first-phase was rapid and consistent, with a median [interquartile-range] viraemia decay of 2.8 [2.6-3.2]. log. IU/ml within 48. h. Second-phase decay was slower, especially in failing patients: 3/3 showed 100. IU/ml at week 2. Only one patient experiencing sustained viral response showed similar kinetics.By pyrosequencing, mutational freeze was observed in all 15 patients within the first 24. h, but only in patients with sustained response afterwards. Indeed, 2/2 failing patients showed early resistance, as minor (V36A-T54A: prevalence
| Original language | English |
|---|---|
| Pages (from-to) | 233-241 |
| Number of pages | 9 |
| Journal | Digestive and Liver Disease |
| Volume | 47 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2015 |
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Keywords
- Drug-resistance
- Mathematical modelling
- Protease inhibitors
- Viral kinetic
ASJC Scopus subject areas
- Gastroenterology
- Hepatology
- Medicine(all)
Cite this
Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice. / Cento, Valeria; Tontodonati, Monica; Di Maio, Velia Chiara; Bellocchi, Maria Concetta; Valenti, Fabrizio; Manunta, Alessandra; Fortuna, Serena; Armenia, Daniele; Carioti, Luca; Antonucci, Francesco Paolo; Bertoli, Ada; Trave, Francesca; Cacciatore, Pierluigi; Angelico, Mario; Navarra, Pierluigi; Neumann, Avidan U.; Vecchiet, Jacopo; Parruti, Giustino; Babudieri, Sergio; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca.
In: Digestive and Liver Disease, Vol. 47, No. 3, 01.03.2015, p. 233-241.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice
AU - Cento, Valeria
AU - Tontodonati, Monica
AU - Di Maio, Velia Chiara
AU - Bellocchi, Maria Concetta
AU - Valenti, Fabrizio
AU - Manunta, Alessandra
AU - Fortuna, Serena
AU - Armenia, Daniele
AU - Carioti, Luca
AU - Antonucci, Francesco Paolo
AU - Bertoli, Ada
AU - Trave, Francesca
AU - Cacciatore, Pierluigi
AU - Angelico, Mario
AU - Navarra, Pierluigi
AU - Neumann, Avidan U.
AU - Vecchiet, Jacopo
AU - Parruti, Giustino
AU - Babudieri, Sergio
AU - Perno, Carlo Federico
AU - Ceccherini-Silberstein, Francesca
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Background: The used first generation protease inhibitors may be hampered by virological failure in partially interferon-sensitive patients. Aim: To investigate early hepatitis C virus (HCV)-RNA decay and quasispecies modifications, and disclose viral dynamics underlying failure. Methods: Viraemia decay at early time-points during telaprevir treatment was modelled according to Neumann et al. (1998). NS3-sequences were obtained by population-sequencing and ultradeep-454-pyrosequencing. Results: 13 treatment-experienced (8 non-responders, 5 relapsers), and two cirrhotic naïve patients, received telaprevir. +. pegylated-interferon-α. +. ribavirin.Viraemia decay was biphasic. In all patients, first-phase was rapid and consistent, with a median [interquartile-range] viraemia decay of 2.8 [2.6-3.2]. log. IU/ml within 48. h. Second-phase decay was slower, especially in failing patients: 3/3 showed 100. IU/ml at week 2. Only one patient experiencing sustained viral response showed similar kinetics.By pyrosequencing, mutational freeze was observed in all 15 patients within the first 24. h, but only in patients with sustained response afterwards. Indeed, 2/2 failing patients showed early resistance, as minor (V36A-T54A: prevalence
AB - Background: The used first generation protease inhibitors may be hampered by virological failure in partially interferon-sensitive patients. Aim: To investigate early hepatitis C virus (HCV)-RNA decay and quasispecies modifications, and disclose viral dynamics underlying failure. Methods: Viraemia decay at early time-points during telaprevir treatment was modelled according to Neumann et al. (1998). NS3-sequences were obtained by population-sequencing and ultradeep-454-pyrosequencing. Results: 13 treatment-experienced (8 non-responders, 5 relapsers), and two cirrhotic naïve patients, received telaprevir. +. pegylated-interferon-α. +. ribavirin.Viraemia decay was biphasic. In all patients, first-phase was rapid and consistent, with a median [interquartile-range] viraemia decay of 2.8 [2.6-3.2]. log. IU/ml within 48. h. Second-phase decay was slower, especially in failing patients: 3/3 showed 100. IU/ml at week 2. Only one patient experiencing sustained viral response showed similar kinetics.By pyrosequencing, mutational freeze was observed in all 15 patients within the first 24. h, but only in patients with sustained response afterwards. Indeed, 2/2 failing patients showed early resistance, as minor (V36A-T54A: prevalence
KW - Drug-resistance
KW - Mathematical modelling
KW - Protease inhibitors
KW - Viral kinetic
UR - http://www.scopus.com/inward/record.url?scp=84924068904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924068904&partnerID=8YFLogxK
U2 - 10.1016/j.dld.2014.12.004
DO - 10.1016/j.dld.2014.12.004
M3 - Article
C2 - 25637450
AN - SCOPUS:84924068904
VL - 47
SP - 233
EP - 241
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
SN - 1590-8658
IS - 3
ER -