Combination Therapy for Chronic Hepatitis C Infection

* INCLUSION CRITERIA: 1. Eighteen years of age or older at screening. 2. Female study participants with childbearing potential (as defined below) and all males must be willing to practice either: * Abstinence from sexual intercourse or * One or more forms of effective barrier contraception throughout dosing and for 30 days following the last dose. This cannot include hormonal contraception for female subjects. Effective forms of barrier contraception include: * a male condom with spermicide * use by female sexual partner of a female condom with spermicide Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) includes any female who: * Has had a hysterectomy or * Has had a bilateral oophorectomy (ovariectomy) or * Is post-menopausal (a demonstration of a total cessation of menses for greater than or equal to1 year) * Has had a bilateral tubal ligation or fallopian tube inserts 3. Chronic HCV GT-1 or GT-4 infection as documented by greater than or equal to 1 measurement of serum HCV RNA greater than or equal to 2,000 international units per milliliter during screening and at least one of the following: * A positive anti-HCV antibody, HCV RNA, or HCV genotype test result greater than or equal to 12 months prior to the baseline (day 0) visit together with current positive HCV RNA and anti-HCV antibody test results or * Positive HCV RNA test and anti-HCV antibody test results together with a liver biopsy consistent with chronic HCV infection or a liver biopsy performed before enrollment with evidence of chronic hepatitis C infection disease, such as the presence of fibrosis. 4. Group A may include up to 20% of subjects with compensated cirrhosis. Group B and C may only include subjects with absence of cirrhosis. Group D, D-ReTx \& E may include subjects with compensated cirrhosis. Group F may only include patients with advanced liver disease (historic Metavir or HAI Stage 3 or 4 or ISHAK Stage 4, 5 or 6 or cirrhosis as defined below) Group G and H may only include those with absence of cirrhosis and HAI Stage 0-2 or FibroTest as below. Cirrhosis is defined as any one of the following: 1. Any biopsy showing cirrhosis. 2. A FibroTest(r) score of greater than or equal to 0.75 AND an AST: platelet ratio (APRI) of \> 2 performed within 12 months of screening. Liver imaging within 6 months of Day 0 to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis. Absence of cirrhosis is defined as one of the following: 1. A liver biopsy performed within 36 calendar months of screening showing absence of cirrhosis. 2. A FibroTest(r) score of \< 0.48 AND APRI of \< 1 performed within 6 months of screening. This would also qualify a subject for Group G and H as having Stage 0-2 disease in the absence of a liver biopsy. In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required (for Groups B, C, G and H). 5. Ability to communicate effectively with the study investigator and other key personnel. 6. Willing to give written informed consent and comply with the study restrictions and requirements. 7. Opioid-dependent individuals must be participating in a supervised treatment program. 8. Subjects must have an external primary care doctor (outside of the CC and the NIH) for their medical management. EXCLUSION CRITERIA: 1. Current or prior history of any of the following: * Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded. * Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug. * Poor venous access interfering with required study blood collection. * Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage). * Solid organ transplantation. * Significant pulmonary disease, significant cardiac disease or porphyria. * Unstable psychiatric disease (Subjects with psychiatric illness that is well-controlled on a stable treatment regimen or currently not requiring medication may be included). * Any malignancy or its treatment that in the opinion of the PI may cause ongoing interference with host immunity; subjects under evaluation for malignancy are not eligible. * Significant drug allergy (such as anaphylaxis or hepatotoxicity). * Substance abuse, which in the opinion of the investigator is likely to interfere with medication adherence or study compliance. * Lactose allergy, patients with lactose intolerance will be evaluated on a case-by-case basis. 2. Positive test results at screening for hepatitis B virus (HBV) surface antigen (HBsAg), HBV DNA (if medically indicated) or anti-HIV antibody (unless previously treated on 13-I-0159). 3. Prior exposure to any direct-acting antivirals for HCV infection, except for patients who were previously treated studies 11-I-0258, 13-I-1059 or this study enrolling in Group D. 4. History of clinically significant chronic liver disease due to other etiology (e.g., hemochromatosis, autoimmune hepatitis, Wilson s disease, alpha 1-antitrypsin deficiency, alcoholic liver disease, \> moderate non-alcoholic steatohepatitis and toxin exposures). 5. Use of herbal/natural remedies for potential benefit to the liver within 21 Days of Day 0. 6. History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease. 7. Screening or baseline ECG with clinically significant ECG findings, or a personal/first degree relative history of Torsade de pointes. 8. Abnormal hematological and biochemical parameters at screening, including: * Neutrophil count less than 750 cells per cubic millimeter. * Hemoglobin level \< 9 g/dL. If Hgb \< 11g/dL in women and \< 12 g/dL in men other causes of anemia should be excluded as medically indicated. * Platelet count less than or equal to 50,000 cells per cubic millimeter. * Estimated glomerular filtration rate less than 50 milliliter/min/1.73m(2). * ALT or AST level greater than or equal to 10 times upper limit of normal (ULN). * Serum lipase level greater than or equal to 1.5 times upper limit of normal (ULN)at screening or during the screening period in a patient with symptoms consistent with pancreatitis. * Total bilirubin level greater than or equal to 2.0 times upper limit of normal (ULN), except in subjects with Gilbert s syndrome. * Albumin level less than or equal to 3.0 grams per deciliter in patients without cirrhosis, albumin less than or equal to 2.8 g/dL in cirrhotic patients. 9. Poorly controlled diabetes mellitus indicated by hemoglobin A1C greater than 9% at screening. 10. Donation or loss of blood of greater than 400 milliliter within 8 weeks prior to the first dose of the study drugs. 11. Known hypersensitivity to GS-5885, GS-7977, GS-9669, GS-9451 or formulation excipients. 12. Pregnant/Breastfeeding women. 13. Need for use of the following medications from 21 days prior to the start of study drugs through the end of treatment (unless otherwise specified): * Hematologic stimulating agents (e.g. erythropoiesis-stimulating agents (ESAs); granulocyte colony stimulating factor (GCSF); thrombopoietin (TPO) mimetics). * Chronic systemic immunosuppressants including, but not limited to, corticosteroids (prednisone equivalent of greater than 10 milligrams per day for greater than 2 weeks), azathioprine, or monoclonal antibodies (e.g., infliximab). * Investigational agents or devices for any indication. * Medications for disease conditions excluded from the protocol (e.g., active cancer, transplantation) are not listed under this Concomitant Medication section and are disallowed in the study. * Concomitant use of certain medications or herbal/natural supplements per PI discretion expected to result in pharmacokinetic interactions resulting in increases or decreases in exposure of study drug(s). 14. Co-enrollment Guidelines: Co-enrollment in other clinical trials is restricted, other than enrollment in observational studies. Study staff should be notified of co-enrollment status, as it may require prior approval of the investigator.