Optimal cure rate by personalized HCV regimens in real-life: a proof-of-concept study

J Antimicrob Chemother. 2017 Dec 1;72(12):3420-3424. doi: 10.1093/jac/dkx302.


Background: Pretreatment evaluation of HCV-infected patients is a complex interplay between multiple clinical and viral parameters, leading to a tailored approach that may bring real-life sustained virological response (SVR) rates close to 98%-99%.

Objectives: As proof-of-concept, we evaluated the efficacy of all-oral direct-acting antiviral (DAA) regimens in patients whose personalization included pre-therapy evaluation of natural resistance-associated substitutions (RASs), in addition to international guideline recommendations.

Methods: One hundred and thirty-one patients who started a first-line all-oral DAA regimen between April 2015 and December 2016 were tested for baseline NS3 and NS5A RASs by Sanger sequencing. SVR12 was defined as HCV-RNA undetectability 12 weeks after treatment discontinuation.

Results: Compatibly with a real-life context, 74.0% (97 of 131) of patients presented ≥2 pretreatment risk factors for failure to achieve SVR12 (infection by GT-1a/GT-3a; cirrhosis; previous treatment experience; HCV-RNA ≥800 000 IU/mL) and 33.6% had ≥3 risk factors. Natural RASs were frequently detected (32.1% prevalence), with substantial prevalence of NS5A RASs (15.3%), mostly represented by Y93H in GT-1b (3 of 36, 8.3%) and GT-3a (3 of 25, 12.0%) and F28C in GT-2c (2 of 11, 18.2%). Overall, personalized treatment led to 100% SVR12, even in those patients for whom treatment strategy was either strengthened (by ribavirin inclusion and/or duration increase) or simplified (by ribavirin exclusion and/or duration reduction), thanks to baseline RAS evaluation.

Conclusions: Even with newer DAA regimens, an integrated interpretation of clinical and virological pretreatment parameters, including natural RASs, may play a relevant role in bringing SVR rates close to the highest achievable. Treatment tailoring can be foreseen in 'hard-to-treat' patients, but also in 'easy' patients with favourable indicators, whereby a simplification/shortening of recommended regimens can be indicated.

MeSH terms

  • Administration, Oral
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacology
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Microbial Sensitivity Tests
  • Precision Medicine / methods*
  • Proof of Concept Study
  • RNA, Viral / blood
  • Sequence Analysis, DNA
  • Sustained Virologic Response
  • Treatment Outcome


  • Antiviral Agents
  • RNA, Viral