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Thématique :
- Foie
Originalité :
Intermédiaire
Solidité :
Très solide
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Docteur Jean-Louis PAYEN
Coup de coeur :
 
 
Journal of Hepatology
  2018/05  
 
  2018 May;68(5):895-903.  
  doi: 10.1016/j.jhep.2017.11.032.  
 
  Resistance analysis in patients with genotype 1–6 HCV infection treated with sofosbuvir/velpatasvir in the phase III studies  
 
  Hezode C, Reau N, Svarovskaia ES, Doehle BP, Shanmugam R, Dvory-Sobol H, Hedskog C, McNally J, Osinusi A, Brainard DM, Miller MD, Mo H, Roberts SK, O'Leary JG, Shafran SD, Zeuzem S  
  https://www.ncbi.nlm.nih.gov/pubmed/29221887  
 
 

Abstract

BACKGROUND & AIMS:

The fixed-dose combination of sofosbuvir/velpatasvir was highly efficacious in patients infected with genotype (GT)1-6 hepatitis C virus (HCV) in the ASTRAL studies. This analysis evaluated the impact of baseline resistance-associated substitutions (RASs) on treatment outcome and emergence of RASs in patients infected with HCV GT1-6 who were treated with sofosbuvir/velpatasvir.

METHODS:

Non-structural protein 5A and 5B (NS5A and NS5B) deep sequencing was performed at baseline and at the time of relapse for all patients treated with sofosbuvir/velpatasvir for 12 weeks (n = 1,778) in the ASTRAL-1-3, ASTRAL-5 and POLARIS-2-3 studies.

RESULTS:

Patients with 37 known and 19 novel HCV subtypes were included in these analyses. Overall, 28% (range 9% to 61% depending on genotype) had detectable NS5A class RASs at baseline, using a 15% sequencing assay cut-off. There was no significant effect of baseline NS5A class RASs on sustained virologic response at week 12 (SVR12) with sofosbuvir/velpatasvir; the SVR12 rate in the presence of NS5A class RASs was 100% and 97%, in patients with GT1a and GT1b infection, respectively, and 100% in patients with GT2 and GT4-6 infections. In GT3 infection, the SVR rate was 93% and 98% in patients with and without baseline NS5A class RASs, respectively. The overall virologic failure rate was low (20/1,778 = 1.1%) in patients treated with sofosbuvir/velpatasvir. Single NS5A class resistance was observed at virologic failure in 17 of the 20 patients.

CONCLUSIONS:

Sofosbuvir/velpatasvir taken for 12 weeks once daily resulted in high SVR rates in patients infected with GT1-6 HCV, irrespective of baseline NS5A RASs. NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients.

LAY SUMMARY:

Sofosbuvir/velpatasvir taken once daily for 12 weeks resulted in high sustained virologic response rates in patients infected with HCV, irrespective of the presence of NS5A resistance-associated variants prior to treatment. Single class NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients.

 

 
Question posée
 
Analyse de résistance chez des patients infectés par le VHC de génotype 1-6 traités par le sofosbuvir / velpatasvir dans les études de phase III.
 
Question posée
 
L’association sofosbuvir/velpatasvir (EpclusaR) pendant 12 semaines en une prise par jour permet des taux élevés de RVS chez les patients infectés par le VHC de génotype 1 à 6, et ce indépendamment des résistances NS5A observées initialement dans 28 % des cas. Une résistance particulière aux inhibiteurs de NS5A a été détectée chez quelques patients présentant une insuffisance virologique. Ces données soulignent la grande barrière à la résistance de cette association thérapeutique.
 
Commentaires

Cet important et minutieux travail réalisé chez un grand nombre de patients traités par cette association nous explique l’excellente efficacité de cette combinaison thérapeutique.

 
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