Journal
JOURNAL OF MEDICAL VIROLOGY
Volume 90, Issue 6, Pages 1094-1098Publisher
WILEY
DOI: 10.1002/jmv.25048
Keywords
genotype 1a; genotype 3; HCV-infection; NS5A; RASs
Categories
Funding
- Fundacion Progreso y Salud, Junta de Andalucia
- Fondo de Investigacion Sanitaria [CM15/00233, CPII14/00014, FI14/00557, PI10/02166, PI13/02266, PI15/00713, PI16/02159]
- GEHEP-SEIMC [GEHEP-004]
- Fundacion Profesor Novoa Santos, A Coruna
- Spanish AIDS Research Network [RD16/0025/0026]
- Plan Nacional de I+D+I
- Fondo Europeo de Desarrollo Regional-FEDER [RD12/0017/006]
- Xunta de Galicia
- European Union [IN606A-2016/023]
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The presence of resistance-associated substitutions (RASs) at NS5A region might compromise the efficacy of Direct Acting Antiviral agents (DAAs). HCV resistance at NS5A region is mainly focused on patients with hepatitis C virus (HCV) genotypes 1a (G1a) and 3 (G3) with other factors of poor treatment response (ie cirrhosis, prior treatment-exposure, or HCV-RNA >800000IU/mL). Herein, we evaluated in a cohort of HCV G1a and G3 infected patients the prevalence of RASs at domain I NS5A using population-based sequencing and the impact of RASs on the optimization of current therapeutic strategies. The RASs considered as clinically relevant were: M28A/G/T, Q30D/E/H/G/K/L/R, L31M/V/F, H58D, and Y93C/H/N/S for G1a and Y93H for G3. A total of 232 patients naive to NS5A inhibitors were included (166 G1a, 66 G3). The overall prevalence of NS5A RASs for G1a and G3 patients was low (5.5%) or null, respectively. A high proportion of patients harbored, at least, one factor of poor response (78.9% for G1a, and 75.8% for G3). Overall, the rates of patients harboring NS5A RASs in combination with any of the other factors were low and the vast majority of patients (G1a>94% and G3 100%) could be treated with standard treatments of 12 weeks without ribavirin. In conclusion, testing NS5A RASs in specific HCV-infected populations (ie G1a & G3, cirrhosis, prior treatment experienced, HCV-RNA >800000IU/mL) might be useful to optimize current NS5A-based therapies avoiding ribavirin-related toxicities, and shortening treatment duration in the majority of patients.
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