Simplifying HCV Treatment in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)

Inclusion Criteria: * Willing and able to provide written informed consent * Age ≥ 18 years * HCV RNA \>1000 IU/mL at Screening * For SOF/VEL arm, HCV treatment-naïve or interferon/ribavirin-experienced * For SOF/VEL/VOX arm, history of virologic failure to SOF/LDV or other DAA-containing regimen as defined by a quantifiable HCV viral load any time at or after the end of HCV therapy * Screening ultrasound excluding hepatocellular carcinoma (HCC) * Acceptable laboratory values including: * Hemoglobin ≥8.0 g/dL * Platelet count ≥40,000/mm3 * AST, ALT, and alkaline phosphatase ≤10 × ULN * Calculated creatinine clearance (CrCl) ≥30 mL/min * General good health * Ability to comply with the dosing instructions for study drug administration and to complete the study schedule of assessments * If HIV-infected: * The participant must have completed at least 6 months of any approved HIV antiretroviral therapy (ART) before starting enrollment * The participant at time of screening and for at least 2 weeks prior to screening must be on ART compatible with SOF/VEL and SOF/VEL/VOX * Screening HIV RNA \< 200 copies/mL * Screening CD4 T-cell count of ≥100 cells/µL * Women of reproductive potential must have a negative urine pregnancy test at Screening and a negative urine pregnancy test at Entry prior to enrollment. Exclusion Criteria: * Current or history of clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage) * Active tuberculosis * Other clinically-significant illness (except HCV and/or HIV) or any other major medical disorder that, in the opinion of the site investigator, may interfere with participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically-significant illness (other than HCV/HIV) are also excluded. * Active Hepatitis B infection * Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy * Pregnant or nursing female * Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment