TY - JOUR
T1 - HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant variants in breakthrough patients assessed by UDPS
T2 - A case study
AU - Bartolini, Barbara
AU - Selleri, Marina
AU - Garbuglia, Anna Rosa
AU - Giombini, Emanuela
AU - Taibi, Chiara
AU - Lionetti, Raffaella
AU - D'Offizi, Gianpiero
AU - Capobianchi, Maria R.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Background: The impact of pre-existing variants in hepatitis C virus (HCV) quasispecies, carrying resistance-associated mutations (RAMs), on the outcome of treatment with direct acting antiviral agents (DAA) is debated and it is complicated by the lack of knowledge of quasispecies distribution between the viral reservoir (liver) and the circulating compartment. Objective: To evaluate NS3 protease heterogeneity and presence of RAMs on baseline plasma and liver biopsy samples. Plasma dynamics were also analyzed during therapy and after its suspension.Study design Ultra-deep pyrosequencing (UDPS) was performed in two HCV genotype 1a patients who received telaprevir (TVR)-based therapy and developed treatment failure due to TVR-resistance. Results: In both patients the baseline diversity of NS3 quasispecies in plasma was higher than in liver (183.6×10-4 vs 47.8×10-4 and 246.0×10-4 vs 55.0×10-4 nt substitution/site, respectively, p
AB - Background: The impact of pre-existing variants in hepatitis C virus (HCV) quasispecies, carrying resistance-associated mutations (RAMs), on the outcome of treatment with direct acting antiviral agents (DAA) is debated and it is complicated by the lack of knowledge of quasispecies distribution between the viral reservoir (liver) and the circulating compartment. Objective: To evaluate NS3 protease heterogeneity and presence of RAMs on baseline plasma and liver biopsy samples. Plasma dynamics were also analyzed during therapy and after its suspension.Study design Ultra-deep pyrosequencing (UDPS) was performed in two HCV genotype 1a patients who received telaprevir (TVR)-based therapy and developed treatment failure due to TVR-resistance. Results: In both patients the baseline diversity of NS3 quasispecies in plasma was higher than in liver (183.6×10-4 vs 47.8×10-4 and 246.0×10-4 vs 55.0×10-4 nt substitution/site, respectively, p
KW - Diversity
KW - HCV
KW - NS3
KW - Resistance associated mutations
KW - Ultra-deep pyrosequencing
KW - Viral quasispecies
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U2 - 10.1016/j.jcv.2015.07.310
DO - 10.1016/j.jcv.2015.07.310
M3 - Article
AN - SCOPUS:84946409452
VL - 72
SP - 60
EP - 65
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
SN - 1386-6532
ER -