A Phase 3, Open-label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Subjects

• Efficacy of SOF + Ribavirin (RBV) [ Time Frame: 12 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
  To determine the efficacy of treatment with SOF + ribavirin (RBV) by proportion of subjects with sustained viral response 12 (SVR 12) after discontinuation of therapy
• Safety and Tolerability of SOF + Ribavirin (RBV) measured by review of accumulated safety data [ Time Frame: Safety and tolerability on treatment and 30 days post last dose ] [ Designated as safety issue: Yes ]
  To evaluate the safety and tolerability of SOF + Ribavirin(RBV) as assessed by review of the accumulated safety data

• Sustained Viral Response at 4 weeks and 24 weeks (SVR4 and SVR 24) [ Time Frame: 4 and 24 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
  To determine the proportion of subjects who attain sustained viral response (SVR) at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
• Emergence of Viral Resistance measured by patients with viral resistance [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  To evaluate the emergence of viral resistance to SOF during treatment and after treatment discontinuation
• Kinetics of circulating HCV RNA during and after treatment discontinuation [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  On treatment and post treatment HCV RNA levels over time will be used to characterize the kinetics of circulating HCV RNA during and after treatment discontinuation.

This is an Open-label Phase 3 study in subjects with chronic Genotype 1, 2, 3, and 4 HCV-infection who are co-infected with HIV-1. A total of 220 HCV subjects who are co-infected with HIV-1 will be enrolled into a single arm and treated with oral SOF 400 mg QD plus weight based RBV (1000 or 1200 mg/day) BID for 12 weeks or 24 weeks. The study population will include HCV genotype 1, 2, 3, and 4 HCV treatment naive subjects (including IFN ineligible) and HCV genotype 2 and 3 HCV treatment experienced subjects who have failed prior therapy with PEG/RBV. Approximately 20% of the subjects enrolled will have evidence of compensated cirrhosis at Screening.

• Chronic Hepatitis C
• Human Immunodeficiency Virus

• Drug: sofosbuvir + Ribavirin (RBV)
  Sofosbuvir (SOF): 400mg; Ribavirin (RBV): 1000 or 1200 mg/day weight based 12 week duration
• Drug: sofosbuvir + Ribavirin (RBV)
  Sofosbuvir (SOF): 400mg; Ribavirin (RBV): 1000 or 1200 mg/day weight based 24 week duration

• Experimental: Arm 1
  Arm 1 ( N= 50) Experimental: SOF + Ribavirin 50 HIV-1/HCV Genotype 2 Treatment Naïve subjects will receive 12 weeks of treatment with SOF (400 mg QD) and RBV (1000-1200 mg daily)
  Intervention: Drug: sofosbuvir + Ribavirin (RBV)
• Experimental: Arm 2
  Arm 2 (n = 50)Experimental: SOF + Ribavirin 50 HIV-1/HCV Genotype 2 and 3 Treatment Experienced subjects will receive 24 weeks of treatment with SOF (400 mg QD) and RBV (1000-1200 mg daily)
  Intervention: Drug: sofosbuvir + Ribavirin (RBV)
• Experimental: Arm 3
  Arm 3 (n=170) Experimental: SOF + Ribavirin 170 HIV-1/HCV Genotype 1, 3 and 4 Treatment Naive subjects will receive 24 weeks of treatment with SOF (400 mg QD) and RBV (1000 1200 mg daily)
  Intervention: Drug: sofosbuvir + Ribavirin (RBV)

Inclusion Criteria:

• Age > or = 18 years with chronic HCV genotype 1, 2, 3, or 4 and co-infected with HIV-1 infection
• HCV RNA > 10,000 IU/mL at Screening
• HCV treatment-naïve for HCV genotypes 1, 2, 3, or 4
• Previous HCV treatment for HCV genotypes 2 or 3
• On a stable, protocol-approved, HIV antiretroviral (ARV) regimen with undetectable HIV-RNA for greater than 8 weeks prior to screening.
• Not currently receiving HIV ARVs
• Presence or absence of cirrhosis; a liver biopsy may be required.
• Healthy according to medical history and physical examination with the exception of HCV and HIV diagnosis.
• Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication.

Exclusion Criteria:

• HCV genotype 1 or 4 with previous HCV treatment
• Poor control with HIV ARV regimen requiring a possible dose modification of therapy within 4 weeks of study medication dosing
• A new AIDS-defining condition diagnosed within 30 days prior to screening
• Prior use of any other inhibitor of the HCV NS5B Polymerase.
• History of any other clinically significant chronic liver disease.
• Evidence of or history of decompensated liver disease.
• Chronic hepatitis B virus (HBV) infection.
• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers).
• Chronic use of immunosuppressive agents or immunomodulatory agents.
• Clinically-relevant drug or alcohol abuse within 12 months of screening.
• History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study or not be in the best interest of the subject in the opinion of the investigator.