Mesa redonda: Hepatite C Novos medicamentos – novos dilemas
Há benefício de Sequenciamento Viral no Retratamento dos pacientes falhados NS5a e IPs?
Fact is that RAVs influence the Therapy. Their presence in HCV is higher than in HIV or HBV. By an amplification rate of 1012 the error rate is about 104 to 105. A sign for this is as well the high amount of 7 genotypes and 67 sub genotypes.
With a small amount of resistant mutants in the beginning of the therapy, they could be eliminated during the therapy or, in some case, they persist and stay with a low viral load. At the end of the therapy they will amplify again and, dependent of the fitness of this mutant, will be substituted by re-mutants to the wild type or persist in the mutant form.
Not all of mutations have a clinical impact. The most important are related to GT1 e GT3. The characteristics of the patient like cirrhosis or previous treatment higher the effect.
Elbasvir/Grazoprevir show this and should not be used in patients with a viral load higher than 800.000 I.U. and Glecaprevir/pibrentasvir should be used for 12 weeks in patient com F3.
Normally it isn’t necessary to test the RAS, but there are exceptions for cirrhotic patients with high viral load and GT1a or GT3. The Polaris-2 study shows, that Sof/Vel gives a SVR12 in this patients and can be used Sof/Vel/Vox for 8 weeks. The majority of DAAs shows a low genetic barrier with high crossed resistance, but Sofosbuvir shows a high barrier.
The use of IP let the RAS persist in GT1a. You can find them in a high number of pretreated patients up to two years. There is a high prevalence in patients pre-treated with DAA. Sof/Vel/Vox seems to be a good choice for this patients. The Magellan study shows that Glecaprevir/Pibrentasvir works good with patients pretreated with IP, but less with NS5A or combination.
There are guidelines for all genotypes with former therapy failures (Sof/Vel/Vox; Gle/Pib, etc. (AASLD/IDSA HCV Guidelines 2018).
The retreatment depends on the previously used drugs and the state of the cirrhosis. Finally conclusion is, that it is not necessary o analyse the mutations, but you have to respect the guidelines in relation to the pretreatment and the situation of the patient.