Patient description: A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Hepatitis C Hepatitis B HIV Infections Ability and willingness of participant to provide informed consent. 2. Men and women age 18 years. 3. Active HCV infection as defined by detectable serum or plasma HCV RNA at any time prior to study entry. Documentation may be obtained from medical records if available. NOTE: If no medical records on HCV infection are available, active HCV infection must be confirmed by a detectable HCV RNA PCR prior to project entry. 4. Allowed HCV treatment history: 1. HCV treatment naïve defined as not having been previously treated for Hepatitis C infection with any medications approved for the treatment of HCV in any country. 2. HCV treatment experienced with interferon with or without ribavirin only (no prior DAA treatment). 5. Chronic Hepatitis B status must be documented by hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) testing. Participants with positive HBsAg must be already on an active HBV regimen at study entry. 6. HIV-1 infection status must be documented as either absent or present, as defined below: 1. Absence of HIV-1 infection, as documented by rapid HIV test or HIV-1 enzyme immunoassay (ELISA) test kit, within 60 days prior to entry. OR 2. Presence of HIV-1 infection, documented by rapid HIV test or HIV-1 ELISA test kit at any time prior to entry. OR 3. HIV-1 infection confirmed by medical documentation as participant is registered in care at AIDS Center and receiving or preparing to initiate ARV treatment. 7. HIV co-infected participants taking ART or planning to initiate ART, should be: 1. Tolerating ART for at least 2 weeks without signs of needing to modify or discontinue the ART regimen before initiating HCV treatment. AND 2. The ART regimen must be a regimen that can be co-administered with SOF/VEL. 8. Participants who are assigned to receive ribavirin as part of the treatment protocol must have hemoglobin ≥11.0 g/dL 9. For females of reproductive potential who will receive ribavirin, a negative urine pregnancy test (urine -HCG with a sensitivity of <25 mIU/mL) within 48 hours prior to project entry (HCV treatment initiation) must be documented. 10. Male and female participants who are able to impregnate or become pregnant (ie, of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control as indicated below or agree to not participate in a conception process while on treatment with ribavirin through at least 12 weeks post-treatment. 11. Life expectancy >12 months, in the opinion of the site investigator  Child-Pugh Score corresponding to Class B or C (decompensated cirrhosis). This requires assessment for encephalopathy and ascites, as well as measurement of serum bilirubin, albumin, and international normalized ratio (prothrombin time). 2. Breastfeeding or pregnancy if patient will be receiving ribavirin. 3. Known allergy/sensitivity or any hypersensitivity to components of drug(s) or their formulation. 4. Acute tuberculosis (TB) infection. They will be followed and offered enrolment when they complete TB treatment. 5. Renal impairment defined as estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 or end-stage renal disease receiving dialysis as treatment with SOF/VEL is contraindicated (https://www.mdcalc.com/mdrd-gfr-equation). 6. Unwilling to provide informed consent for participation in the project. 7. Prior treatment with any HCV Direct Acting Agents (DAA). 8. Unable or unwilling to adhere to the HCV treatment course and monitoring in the opinion of the investigator