Sofosbuvir-Containing Regimens Without Interferon For Treatment of Acute Hepatitis C Virus (HCV) Infection

A5327 Eligibility Criteria (Cohort 1 and Cohort 2)

Step 1 inclusion criteria for both cohorts (Cohort 1 and Cohort 2)

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load. [NOTE: The term "licensed" refers to a FDA-approved kit, which is required for all IND studies.] WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• A documented confirmation of acute HCV infection within 6 months prior to A5327 entry or HCV reinfection as described below:
• Acute HCV infection was defined as meeting one of the following criteria and exclusion of other causes of acute hepatitis:
• New ( 250 U/L in patients with documented normal ALT in the preceding 12 months or ≥10X ULN OR >500 U/L in patients with abnormal or no measured ALT baseline in the preceding 12 months with detectable HCV RNA excluding those with any prior positive anti-HCV. OR
• Detectable HCV RNA with prior negative anti-HCV Ab or undetectable HCV RNA within the preceding 6 months.
• Acute HCV reinfection was defined by documentation of clearance of prior infection (as evidenced by positive anti-HCV Ab) either spontaneously or after treatment with two negative HCV RNA a minimum of 6 months apart AND meeting one of the following criteria in addition to exclusion of other causes of acute hepatitis:
• New ( 250 U/L in patients with documented normal ALT in the preceding 12 months or ≥10X ULN OR >500 U/L in patients with abnormal or no measured ALT baseline in the preceding 12 months with detectable HCV RNA. OR
• Positive HCV RNA with prior negative HCV RNA within the preceding 6 months.
• HCV RNA confirmed to be detectable >12 weeks after first laboratory evidence of acute HCV and still within the 500 cells/mm3) or (2) decision by provider and participant to defer ARV therapy during the study drug dosing period (8 or 12 weeks), or (3) elite controller (CD4+ >200 cells/mm3). OR
• On a stable, protocol-approved (didanosine (ddI), stavudine (d4T), zidovudine (ZDV) excluded), ARV regimen for >8 weeks prior to screening with a CD4 T-cell count >200 cells/mm3 and a documented plasma HIV-1 RNA level 50 copies/mL by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent ≥ 8 weeks preceding the A5327 screening visit. HIV-1 RNA levels should be within 1 year of the screening visit. Screening HIV-1 RNA must be 500 cells/mm3) or (2) decision by provider and participant to defer ARV therapy during the study drug dosing period (8 or 12 weeks), or (3) elite controller (CD4+ >200 cells/mm3). OR
• On a stable, protocol-approved ARV regimen (the following ARVs are not allowed: ddI, d4T, and TPV/r) for >8 weeks prior to screening with a CD4 T-cell count >200 cells/mm3 and a documented plasma HIV-1 RNA level 50 copies/mL by any laboratory that had a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent ≥ 8 weeks preceding the A5327 screening visit. HIV-1 RNA levels should be within 1 year of the screening visit. Screening HIV-1 RNA must be 10 mg/day).
• History of solid organ transplantation.
• Current or prior history of clinical hepatic decompensation (eg, ascites, encephalopathy or variceal hemorrhage).
• History of a gastrointestinal disorder (or post operative condition) that could inter