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

A5327 Eligibility Criteria (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:

1. Acute HCV infection was defined as meeting one of the following criteria and exclusion of other causes of acute hepatitis:

* New (\<24 weeks prior to initial A5327 entry) ALT elevation to ≥5X upper limit of normal (ULN) OR \>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.

2. 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 (\<24 weeks prior to initial A5327 entry) ALT elevation to ≥5X ULN OR \>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 \<24 week from first laboratory evidence of acute HCV infection window. First laboratory evidence of infection was defined as date of first elevated liver enzymes or date of first serologic evidence of HCV seroconversion and/or viremia (whichever occurs first). \[NOTE: If the screening visit occurred less than 12 weeks from the first laboratory evidence of infection, then the participant was required a pre-entry study visit to confirm detectable HCV RNA at least 12 weeks from the first laboratory evidence of infection had passed. It was optimal for this pre-entry visit to occur as close as possible to 12 weeks from first laboratory evidence to ensure timely treatment. Potential participants who entered screening but who had an undetectable HCV RNA (\<LLOQ TND) at the pre-entry visit (when required) exhibited evidence of possible spontaneous clearance and will not meet the entry criteria.\]

Body mass index (BMI) ≥ 18 kg/m\^2

Screening electrocardiogram (ECG) without clinically significant abnormalities as determined by the investigator.

Willing and able to provide written informed consent.

Men and women age ≥ 18 years.

HIV-1 ARV therapy fell into one of the following criteria:

1. ARV untreated, for example due to (1) lack of indication per provider (CD4 T-cell count \>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

2. 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 or \< lower limit of quantification (LLOQ) of local assay if LLOQ is \>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 \< 50 copies/mL as measured by any local laboratory using an FDA-approved assay.

Candidates must have had the following laboratory parameters within 10-42 days prior to study entry:

1. Hemoglobin ≥ 12 g/dL for male, ≥11 g/dL for female participants

2. International normalized ratio (INR) ≤1.5 x ULN unless participant was known hemophilia or was stable on an anticoagulant regimen affecting INR

3. Albumin ≥ 3 g/dL

4. Creatinine clearance (CrCl) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation (refer to section 6.3.5 for calculator utility link)

Female participants of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who had not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must had a negative serum pregnancy test with a sensitivity of at least 25 mIU/mL performed during screening, within 48 hours prior to study entry.

HCV genotype 1a, 1b, or 4 infection with source documentation from a CLIA-approved laboratory (or its equivalent). \[NOTE: Those with mixed 1a/b genotype were classified as 1a.\]

HIV-1 ARV therapy fell into one of the following criteria:

1. ARV untreated, for example due to (1) lack of indication per provider (CD4 T-cell count \>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

2. 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 or \<LLOQ of local assay if LLOQ is \>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 \<50 copies/mL as measured by any local laboratory using an FDA-approved assay.

Candidates must have had the following laboratory parameters within 10-42 days prior to study entry:

1. Hemoglobin ≥9 g/dL for male and female participants

2. International normalized ratio (INR) ≤1.5 x ULN unless participant had known hemophilia or wass stable on an anticoagulant regimen affecting INR

3. Albumin ≥3 g/dL

4. Creatinine clearance (CrCl) ≥60 mL/min, as calculated by the Cockcroft-Gault equation (refer to section 6.3.5 for calculator utility link)

Female participants of reproductive potential (defined as women who had not been post-menopausal for at least 24 consecutive months, ie, who had menses within the preceding 24 months, or women who had not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy) must had a negative serum or urine pregnancy test within 48 hours prior to study entry by any laboratory or clinic that had a CLIA certificate or its equivalent, or was using a point-of-care (POC)/CLIA-waived test. The serum, urine or POC pregnancy test must had a sensitivity of at least 25 mIU/mL.

What this study is about