STOP HCV-1 – Stratified Treatment Optimisation for HCV-1

INTERVENTION: The main intervention being compared in all patients is varying (4‐6 weeks) duration of treatment (ombitasvir/paritaparevir/dasabuvir/ritonavir (Viekirax)) determined by the participant’s screening viral load with or without ribavirin Vs fixed (8 weeks) duration of the same treatment with or without ribavirin. All the treatments in this study are taken orally and are approved for treatment of chronic Hepatitis C. First‐line treatment ombitasvir/paritaprevir/ritonavir (two tablets once daily) plus dasabuvir (one tablet twice daily) with or without ribavirin (2 or 3 tablets twice daily) will be taken for: 1. 8 weeks 2. 4‐6 weeks The duration of treatment will be chosen based on a computerised randomisation program. One group of people will all get 8 weeks initial treatment. In the other group, people with less virus in their blood will get less treatment. Because there is less virus in the blood, less drug should be needed to kill it all – this is what the study is testing. If participants fail first‐line treatment they will be offered 12 week treatment with sofosbuvir/ledipasvir (Harvoni) with ribavirin. Follow‐up of all treatment arms will be 24 weeks post end of treatment first line or retreatment. CONDITION: Specialty: Infectious diseases and microbiology, Primary sub‐specialty: Infectious diseases and microbiology (migration; UKCRC code/ Disease: ; Infections and Infestations ; Hepatitis C infection PRIMARY OUTCOME: 1. Sustained Virological Response, measured by HCV viral load through 12 weeks after the end of combined first‐line and any retreatment phases; 2. Sustained Virological Response measured by HCV viral load through 12 weeks of first line treatment for the ribavirin comparison SECONDARY OUTCOME: 1. Sustained virological response, measured by HCV viral load through 24 weeks after the end of combined first‐line and any retreatment phases; 2. Sustained virological response, measured by HCV viral load through 24 weeks after first‐line treatment only; 3. Lack of any virological response, measured by HCV viral load at any time point in the study; 4. Viral load rebound after becoming undetectable at any time point in the study; 5. Serious Adverse Events at any time point during the study ; 6. Grade 3 or 4 adverse events at any time point during the study; 7. Adverse events of any grade judged to be definitely or probably related to the study interventions at any time point during the study; 8. Any toxicity which leads to a modification of study treatment at any time point during the study; 9. Development of grade 3 or 4 anaemia at any time point during the study; 10. Emergence of resistance‐associated HCV variants in participants in the duration of the study INCLUSION CRITERIA: 1. Aged =18 years 2. Infected with HCV genotype 1a or 1b with HCV RNA >LLOQ (lower limit of quantification) on more than one occasion at least six months previously with no intervening results showing undetectable viraemia 3. Plasma HCV RNA >LLOQ at screening 4. No evidence of significant liver fibrosis resulting from any aetiology (defined as Fibroscan* score =7.1kPa, equivalent to F0‐F134, within 180 days prior to planned randomisation or biopsy consistent with mild fibrosis (Ishak score <=2/6) within 180 days prior to planned randomisation) 5. BMI >=18kg/m2 6. Laboratory tests: platelets >=60x109/l, haemoglobin >12g/dl (male) or >11g/dl (female), creatinine clearance (estimated glomerular filtration rate (eGFR) (Cockcroft‐Gault)) >=60ml/min, international normalised ratio (INR) <1.5xULN 7. Screening HCV viral load <10,000,000IU/ml 8. Written informed consent obtained from the patient If HIV infected, then an additional eligibility cri