deLIVER: Direct Acting Antiviral Effects on the Liver

Inclusion Criteria Participants must meet all of the following inclusion criteria to be eligible for participation

• Ability and willingness of participant to provide written informed consent.
• Men and women age ≥18 to ≤70 years at study entry
• Body mass index (BMI) ≥ 18 kg/m2
• HCV RNA ≥ 10, 000 IU/mL at Screening
• HCV genotype 1a at Screening or within 6 months of screening
• Chronic HCV infection (≥ 6 months) documented by prior medical history
• HCV treatment-naïve with no prior treatment with any IFN, RBV, or approved or experimental HCV-specific DAA
• Absence of cirrhosis as defined as transient elastography (FibroScan®) liver stiffness measurement 10 g/dL for men and > 9 g/dL for women
• Platelet count ≥90,000/mm3
• International normalized ratio (INR) ≤1.5
• Calculated creatinine clearance (CrCl) ≥ 30 mL/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase level ≤ 10 x upper limit of the normal range (ULN)
• Total bilirubin <3 mg/dL
• Albumin ≥3.5 g/dL
• CD4+ cell count ≥200 cells/uL and CD4+ cell percentage ≥14% within 42 days of study entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification [HIV seropositive participants only]
• HIV RNA < 400 copies/mL prior to study entry by any US laboratory that has a CLIA certification or its equivalent [HIV seropositive participants only]
• On a qualifying antiretroviral therapy (ART) regimen which is permitted with SOF/VEL. This allows for antiretroviral regimen that does not include Efavirenz, Nevirapine, or Tipranavir.
• Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 0 prior to liver biopsy
• All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).
• If participating in sexual activity that could lead to pregnancy, the participant (men and women) must also agree to use two reliable methods of contraception simultaneously while receiving study treatment and for 30 days after stopping study treatment.

A combination of TWO of the following contraceptives MUST be used appropriately:

• Condoms (male or female) with or without a spermicidal agent
• Diaphragm or cervical cap with spermicide
• IUD (intrauterine device)
• Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives. Acceptable documentation of sterilization and menopause is specified below.

Written or oral documentation communicated by clinician or clinician's staff of one of the following:

• Physician report/letter
• Laboratory report of azoospermia
• Follicle stimulating hormone-release factor (FSH) measurement elevated into the menopausal range as established by the reporting laboratory.
• Participants must be able to adhere to dosing instructions for study drug administration and able to complete the study schedule of assessments, in the opinion of the investigator.

Exclusion Criteria

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

• Breastfeeding.
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
• Acute or serious illness requiring systemic treatment and/or hospitalization within 42 days prior to study entry.
• Active hepatitis B infection (positive HBsAg) within 42 days prior to study entry.
• History of decompensated liver disease (including but not limited to encephalopathy, variceal bleeding, or ascites) prior to study entry.
• Any cause of liver disease other than chronic HCV infection, including but not limited to the following:
• Hemochromatosis
• Alpha-1 antitrypsin d