• Complete early virologic response (cEVR), defined as undetectable hepatitis C virus (HCV) RNA at 12 weeks after initiation of nitazoxanide (NTZ) + peginterferon alpha-2a (PEG-IFN) + ribavirin (RBV) [ Time Frame: Measured at Week 16 ] [ Designated as safety issue: Yes ]
  
• Early virologic response (EVR), defined as undetectable HCV RNA or decrease in HCV RNA greater than or equal to 2 log10 from baseline after 12 weeks of NTZ + PEG-IFN + RBV [ Time Frame: Measured at Week 16 ] [ Designated as safety issue: Yes ]
  

• Sustained virologic response (SVR), defined as undetectable HCV RNA [ Time Frame: Measured 24 weeks after treatment discontinuation ] [ Designated as safety issue: Yes ]
  
• Rapid virologic response (RVR), defined as undetectable HCV RNA at 4 weeks after initiation of NTZ + PEG-IFN + RBV [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: Yes ]
  
• Adverse events of at least grade 2 severity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Hemoglobin of all levels [ Time Frame: Measured every 4 weeks for 52 weeks and at Weeks 64 and 76 ] [ Designated as safety issue: No ]
  
• Fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance (HOMA-IR) [ Time Frame: Measured at entry and Weeks 16, 28, 52, and 76 ] [ Designated as safety issue: No ]
  
• In vitro assessment of interferon (IFN)-responsive proteins from stored peripheral blood mononuclear cells (PBMCs) [ Time Frame: Measured every 4 weeks for 52 weeks, and at Weeks 64 and 76 ] [ Designated as safety issue: No ]
  
• Change in HCV RNA after NTZ monotherapy [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
  
• HCV genotype results, found by testing stored plasma [ Time Frame: Measured at baseline and at Week 4 ] [ Designated as safety issue: No ]
  

Chronic hepatitis C virus (HCV) is a significant cause of liver scarring, or cirrhosis, and accounts for up to 30% of all liver transplants in the United States. People infected with HIV are at a high risk of coinfection with HCV, and the combination of these two infections appears to accelerate progression to cirrhosis. Current treatment for HCV infection includes a 48-week course of two medications taken together, peginterferon alfa-2a (PEG-IFN) and ribavirin (RBV). This combination is only effective in 14% to 29% of people infected with both HIV and HCV genotype 1 (the genotype most common in the United States). Further complicating treatment, antiretrovirals (which are used to treat HIV) and HCV medications can often have high toxicity when taken together, limiting dosing.

Nitazozanide (NTZ) is a medication currently approved to treat intestinal infections that is being investigated for use in treating HCV. NTZ has few side effects and has been shown to increase effectiveness of HCV treatment when combined with PEG-IFN and RBV. This study will test whether adding NTZ to current regimens for people coinfected with HCV and HIV will improve HCV treatment outcomes.

Participation in this study will last 76 weeks. At study entry, participants will complete a brief physical exam, provide a urine sample for a routine safety test, provide a blood sample, and complete a pregnancy test. Participants will then receive NTZ, which they will take twice a day with food for the next year. After 4 weeks on NTZ, participants will complete a second study visit, at which they will complete the same assessments as at study entry and be asked about the medications they are taking. At this visit participants will receive the other two study drugs, PEG-IFN and RBV. PEG-IFN will be delivered via injection weekly and RBV will be taken orally twice a day.

Participants will take NTZ, PEG-IFN, and RBV together for the next 48 weeks. During this time, participants will complete study visits every 4 weeks until study Week 52 and then complete follow-up visits at Weeks 64 and 76. At these visits, participants will complete the same assessments as in previous visits, and, on certain weeks, will also fast for 8 hours before blood draw. Additional blood samples will be taken and stored on Weeks 12, 28, and 40 in order to do future testing. Participants who do not experience an early response to the treatment given will stop early, after about 20 weeks.