Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in PWID and People With HIV Coinfection.

Inclusion Criteria

• Subjects must meet all of the following inclusion criteria to be eligible to participate in this study:
• Participants have voluntarily signed the informed consent form.
• 18 years of age or older.
• Detectable HCV RNA at screening (>10, 000 IU/ml), and in the opinion of the investigator is unlikely to demonstrate spontaneous viral clearance
• HCV genotypes 1-6.
• HBsAg negative
• Compensated liver disease (Child-Pugh A)
• Negative pregnancy test at baseline (females of childbearing potential only).
• Medically stable on the basis of physical examination, medical history and vital signs
• Adequate English to provide reliable responses to the study questionnaires
• All fertile males and females must be using effective contraception during treatment and during the 30 days after treatment end.
• Recently acquired HCV infection (estimated duration of infection ≤12 months)*

Recently acquired HCV infection as defined by:

A) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Documented anti-HCV Ab negative within the 12 months prior to anti-HCV antibody positive result

OR

B) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Acute clinical hepatitis [jaundice or alanine aminotransferase (ALT)] > 10 X ULN) within the previous 6 months prior to first positive HCV antibody or HCV RNA, with no other cause of acute hepatitis identifiable

OR

C) For cases of recent HCV reinfection the following criteria are required:

Documented prior HCV antibody positive with HCV RNA negative on at least 2 occasions 6 months apart AND new HCV RNA positive within the previous 6 months

*Estimated duration of infection based on midpoint between last antibody negative or HCV RNA and first antibody positive or HCV RNA in the case of seroconversion and 6 weeks prior to date of maximum ALT in the case of acute hepatitis.

If co-infection with HIV is documented, the subject must meet the following criteria:

• Antiretroviral (ARV) untreated for >8 weeks preceding screening visit with cluster of differentiation 4 (CD4) T cell count >500 cells/mm3 OR
• On a stable ARV regimen for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and an undetectable plasma HIV RNA level.
• Suitable ARV include:
• Tenofovir (TDF) and tenofovir alafenamide (TAF)
• Emtricitabine (FTC)
• Rilpivirine
• Dolutegravir
• Elvitegravir/cobicistat
• Contraindicated ARV include:
• Efavirenz 50% reduction in velpatasvir (GS-5816) exposure
• Didanosine
• Zidovudine
• Tipranavir Other ARV agents may be permissible at the time of study commencement pending further drug-drug interaction studies; please discuss with Study Principal Investigator.

Exclusion criteria

Subjects who meet any of the exclusion criteria are not to be enrolled in this study.

• History of any of the following:
• Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded.
• History of chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
• Solid organ transplant
• Malignancy within 5 years prior to screening, with exception of specific cancers that may have been cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are also excluded.
• Significant drug allergy (such as anaphylaxis or hepatotoxicity).
• Subject shows evidence of significant liver disease in addition to hepatitis C, which may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune hepatitis, he