Directly Observed Therapy for HCV in Chennai, India

Inclusion Criteria: 1. Willing/able to provide consent 2. Age ≥ 18 3. Chronic HCV (HCV RNA positive) 4. Resident of Chennai and can provide locator information 5. If co-infected with HIV, must have CD4 (Cluster of Differentation 4) \> 350 cells/mm3 and either: 1) ART naïve or 2) if on ART be on a tenofovir-containing regimen. If a participant's CD4 drops below 350 cells/μl (threshold for treatment in India), will have to initiate a tenofovir-containing regimen (current standard of care). 6. Participants must have the following at screening: 1. Alanine Aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN) 2. Aspartate Aminotransferase (AST) ≤ 10 x ULN 3. Hemoglobin ≥ 12 g/dl for males and 11 g/dl for females 4. International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR 5. Albumin ≥ 3 g/dl 6. Direct bilirubin ≤ 1.5 x ULN 7. Creatinine clearance ≥ 60 ml/min (Cockgroft-Gault Equation) 8. Alpha fetoprotein \< 50 ng/ml 9. Absolute neutrophil count (ANC) ≥ 1,500/μL 10. Platelets ≥ 90,000/μL 11. Thyroid stimulating hormone (TSH) ≤ ULN 7. A female subject is eligible if it is confirmed that she is: 1. Not pregnant or nursing 2. Of non-childbearing potential (i.e., women who have had hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal women \> 50 years of age with cessation (for ≥12 months) of previously occurring menses 3. Of childbearing potential and negative urine pregnancy test prior to randomization and agree to one of the following from 3 weeks prior to Baseline/Day 1 until 6 months after the last dose of RBV. * Complete abstinence from intercourse. Or • Consistent use of approved methods of birth control in addition to a male partner who correctly uses a condom from 3 weeks prior to Baseline/Day 1 until 6 months after the last dose of RBV. 8. Male participants must agree to consistently and correctly use a condom. If their female partner is of childbearing potential, their partner must agree to use one of the study approved non-hormonal methods of birth control or a hormone-containing contraceptive, from the date of screening until 7 months after their last dose of RBV 9. Male participants must agree to refrain from sperm donation for at least 7 months after the last dose of RBV. 10. Of generally good health as determined by the investigator. 11. Able to comply with the dosing instructions for study drug administration and willing to complete the study schedule of assessments. Exclusion Criteria: 1. Pregnant/nursing female or male with pregnant/nursing female partner. 2. Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage, MELD\<12) 3. Prior hepatitis C treatment 4. Infection with hepatitis B virus 5. Chronic use of systematically administered immunosuppressive agents (e.g., prednisone equivalent \>10 mg/day) 6. Use of any prohibited concomitant medications within 28 days of the Baseline/Day 1 visit. 7. Contraindications to RBV therapy or PEG/RBV 8. Known hypersensitivity to RBV or PEG, the metabolites or formulation excipients 9. Additional exclusion criteria related to Aim 1 regimen 1. Pre-existing significant psychiatric condition(s) including severe depression, severe bipolar disorder and schizophrenia. Other psychiatric disorders are permitted if the condition is well controlled with a stable treatment regimen for ≥ 1 year from screening. 2. Presence of autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis). 3. History of clinical significant retinal disease.