RESUMEN
High rates of sustained virologic response at post-treatment week 12 (SVR12) were achieved in six phase 3 trials of ombitasvir (OBV, an NS5A inhibitor), paritaprevir (an NS3/4A protease inhibitor) co-dosed with ritonavir (PTV/r) + dasabuvir (DSV, an NS5B RNA polymerase inhibitor) (ie, 3D regimen) with or without ribavirin (RBV) in adults with chronic genotype (GT) 1 hepatitis C virus (HCV) infection. We assessed whether time to first HCV RNA value below the lower limit of quantification in patients with and without cirrhosis was associated with achievement of SVR12. Data were analysed from GT1-infected patients enrolled in six phase 3 studies of 3D ± RBV. Patients who experienced non-virologic failure were excluded from analysis. HCV RNA was determined using the Roche COBAS TaqMan RT-PCR assay (lower limit of quantification, LLOQ =25 IU/mL). SVR12 was analysed by week of first HCV RNA suppression, defined as HCV RNA Asunto(s)
Antivirales/administración & dosificación
, Genotipo
, Hepacivirus/clasificación
, Hepatitis C Crónica/tratamiento farmacológico
, Hepatitis C Crónica/virología
, Respuesta Virológica Sostenida
, Adolescente
, Adulto
, Anciano
, Anilidas
, Carbamatos
, Ensayos Clínicos Fase III como Asunto
, Femenino
, Hepacivirus/genética
, Hepacivirus/aislamiento & purificación
, Humanos
, Masculino
, Persona de Mediana Edad
, Prolina
, ARN Viral/sangre
, Factores de Tiempo
, Resultado del Tratamiento
, Valina
, Adulto Joven
RESUMEN
The treatment for patients infected with hepatitis C virus (HCV) genotype 1 has undergone major changes with the availability of direct-acting antivirals. Triple therapy, containing telaprevir or boceprevir, first-wave NS3 protease inhibitors, in combination with peginterferon and ribavirin, improved rates of sustained virologic response compared with peginterferon and ribavirin alone in patients with HCV genotype 1. However, the development of drug-resistant variants is a concern. In patients treated with telaprevir or boceprevir, different patterns of resistance are observed for the two major HCV genotype 1 subtypes, 1a and 1b. Genotype 1b is associated with a lower rate of resistant variant selection and better response to triple therapy compared with genotype 1a. Similar subtype-specific patterns have been observed for investigational direct-acting antivirals, including second-wave NS3 protease inhibitors, NS5A inhibitors and non-nucleoside NS5B inhibitors. This review explores resistance to approved and investigational direct-acting antivirals for the treatment of HCV, focusing on the differences between genotype 1a and genotype 1b. Finally, given the importance of HCV genotype 1 subtype on resistance and treatment outcomes, clinicians must also be aware of the tests currently available for genotype subtyping and their limitations.
Asunto(s)
Antivirales/uso terapéutico , Farmacorresistencia Viral/genética , Hepacivirus/genética , Hepatitis C/virología , Quimioterapia Combinada , Genotipo , Hepacivirus/clasificación , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Oligopéptidos/uso terapéutico , Polietilenglicoles/uso terapéutico , Prolina/análogos & derivados , Prolina/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Ribavirina/uso terapéutico , Especificidad de la Especie , Resultado del TratamientoRESUMEN
I have become involved in the setting up of an epilepsy self- help group in the town of Tiverton. Because of my experience over many years as the mother of two daughters who both suffer from chronic epilepsy I have been asked to be an adviser to other parents of newly diagnosed children.