HCV DAA Failure Study

• Research type

  Research Study

• Full title

  Detection of minority variants and their association with success or failure of direct acting antiviral therapy (DAA) in individuals with hepatitis C infection (HCV).

• IRAS ID

  161793

• Contact name

  Mark Nelson

• Contact email

  mark.nelson@chelwest.nhs.uk

• Sponsor organisation

  Imperial College London

• Duration of Study in the UK

  1 years, 9 months, 31 days

• Research summary

  Direct-acting antivirals (DAAs) are a group of new drugs which has been developed to treat the infection caused by hepatitis C virus (HCV), thereby increasing cure rates in HCV infection to between 80-100 % in clinical trials by successfully interfering with specific steps in HCV’s life cycle.
  When HCV replicates every day, it makes mistakes in the copying of its genetic material (mutations) which can result in drug resistance of HCV. Sequencing (the process of determining the genetic code of the virus) can be used to detect drug resistance prior to treatment. Standard sequencing methods detect only the most common viral population which may be drug sensitive. However, subpopulations resistant to the direct-acting antiviral drugs against HCV may coexist undetected. Next generation sequencing is a highly sensitive method which can detect many viral sequences or populations in the blood, not just the dominant code.
  Little is known about the relevance of DAA-resistance in individuals with HCV infection who fail treatment. DAA-associated mutations may occur in patients who have been previously treated with DAAs, known as acquired resistance. Transmission of these mutations needs highlighting as it may impair future therapeutic interventions. We will conduct a retrospective study of HCV-infected patients who have been treated with DAA's, using next generation sequencing technology to detect DAA-resistant forms of HCV. We propose to study, with ethical approval, existing plasma samples from these patients that have been collected for diagnostic purposes but are no longer required. A pre-treatment diagnostic sample will be tested for resistance on all patients and if HCV is detected after treatment has started, a second sample will also be tested.

• REC name

  London - Bromley Research Ethics Committee

• REC reference

  14/LO/2227

• Date of REC Opinion

  16 Dec 2014

• REC opinion

  Favourable Opinion