Nitazoxanide Plus Ribavirin and Peginterferon for Therapy of Treatment Naive HCV Genotype 1 and HIV Coinfected Subjects

• Percentage of Participants With Complete Early Virologic Response (cEVR) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  Complete early virologic response (cEVR) was defined as undetectable HCV viral load (<43 IU/ml) at week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).
  
  
• Percentage of Participants With Early Virologic Response (EVR) [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  Early virologic response (EVR) was defined as undetectable HCV viral load (<43 IU/ml) at Week 16 or at least a 2-log10 decrease in HCV viral load from study entry at Week 16, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).
  
  

• Percentage of Participants With Sustained Virologic Response (SVR) [ Time Frame: 24 weeks after treatment discontinuation ] [ Designated as safety issue: No ]
  Sustained virologic response (SVR) is defined as undetectable HCV viral load (<43 IU/ml) at 24 weeks after treatment discontinuation, where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).
  
  
• Percentage of Participants With Rapid Virologic Response (RVR) [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
  Rapid virologic response (RVR) was defined as undetectable HCV viral load (<43 IU/ml) at Week 8 where 43 is the lower limit of quantification of the assay (Cobas AmpliPrep/Taqman HCV Test).
  
  
• Number of Participants With Adverse Events of Grade 2 or Higher [ Time Frame: From study entry to up to week 76 ] [ Designated as safety issue: Yes ]
  Number of participants who experienced an adverse event of Grade 2 or higher at any time after study entry. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.
  
  
• Change in Hemoglobin Level From Study Entry [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76. ] [ Designated as safety issue: Yes ]
  Change in hemoglobin (HGB) was calculated as HGB at later time point (Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 76) minus HGB at study entry.
  
  
• Fasting Insulin Level [ Time Frame: Weeks 0, 16, 28, 52, and 76 ] [ Designated as safety issue: No ]
  
• Fasting Glucose Level [ Time Frame: Weeks 0, 16, 28, 52, and 76 ] [ Designated as safety issue: No ]
  
• Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Weeks 0, 16, 28, 52, and 76 ] [ Designated as safety issue: No ]
  
• Change in log10 HCV Viral Load After 4 Weeks of Nitazoxanide (NTZ) Monotherapy. [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  Change in log10 HCV viral load was calculated as log10-transformed HCV viral load at Week 4 minus log10-transformed HCV viral load at study entry. HCV viral load testing was done using Cobas AmpliPrep/Taqman HCV Test.
  
  
• Number of Participants With HCV Genotype 1 [ Time Frame: Week 0 ] [ Designated as safety issue: No ]
  HCV genotyping will be performed on stored plasma from entry to confirm HCV genotype 1.
  
  
• Number of Subjects With Interferon (IFN)-Responsive Proteins Present in Stored Peripheral Blood Mononuclear Cells (PBMCs) Based on In Vitro Assessment. [ Time Frame: Every 4 weeks from entry to Week 52, and at Weeks 64 and 76 ] [ Designated as safety issue: No ]
  Number of Subjects with Interferon (IFN)-Responsive Proteins Present in Stored Peripheral Blood Mononuclear Cells (PBMCs) Based on In Vitro Assessment. Additional endpoint for supportive/exploratory analyses that will be defined in more detail in a separate analysis plan.
  
  

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) 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.

Nitazoxanide (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 and RBV among HCV monoinfected people. This study will test whether adding NTZ to PEG+RBV regimen for people coinfected with HCV and HIV improves HCV treatment outcomes.

Participation in this study will last up to 76 weeks. At study entry, participants completed a brief physical exam, provided a urine sample for a routine safety test, provided a blood sample, and completed a pregnancy test. Participants then initiated NTZ, which they took twice a day with food for up to a year. After 4 weeks on NTZ, participants completed the second study visit, at which they completed the same assessments as at study entry and were asked about the medications they were taking. At this visit, participants initiated the other two study drugs, PEG and RBV. PEG was delivered via injection weekly and RBV was taken orally twice a day with dose dependent on participant's weight at entry.

Participants took NTZ, PEG and RBV together for up to 48 weeks. During this time, participants completed study visits every 4 weeks until Week 52 and then completed follow-up visits at Weeks 64 and 76. At these visits, participants completed the same assessments as at previous visits, and, at certain weeks, also fasted for 8 hours before blood draw. Additional blood samples were collected and stored at Weeks 4, 8, 16, 52 and 76 in order to do future testing.

Participants who did not achieve an early virologic response to the study treatment (at least a 2-log10 decrease in HCV viral load or undetectable HCV viral load at Week 16), or had detectable HCV viral load at Week 28), stopped study treatment and discontinued study early, at about 20 or 32 weeks, respectively.