Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV)

Inclusion Criteria for Step 1:

• HIV infected
• Stable antiretroviral therapy for at least 8 weeks prior to study entry OR have not received any antiretroviral therapy for at least 4 weeks prior to entry
• HIV viral load less than 50, 000 copies/ml within 6 weeks prior to study entry
• CD4 count greater than 200 cells/mm^3 within 6 weeks prior to study entry
• Hepatitis C virus (HCV) infected
• Either HCV treatment naive OR previously treated with interferon (IFN), PEG-IFN, IFN and ribavirin, or PEG-IFN and ribavirin for at least 12 weeks and HCV RNA positive following their last course of HCV treatment
• Chronic liver disease consistent with chronic viral hepatitis
• At least stage I fibrosis on a liver biopsy obtained within 104 weeks of study entry
• If at stage VI fibrosis, Child-Pugh-Turcotte (CPT) score of 5 or less and no more than Child-Pugh Class A
• Liver enzyme (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase) levels 10 times or less than upper limit of normal
• Agree to use acceptable methods of contraception

Inclusion Criteria for Step 2:

• Currently enrolled in Step 1 or received 12 weeks of PEG-IFN plus ribavirin outside this study
• Detectable HCV viral load and <2 log10 decrease from baseline in plasma/serum HCV viral load at Week 12.
• On Step 1 study treatment for no longer than 18 weeks

Inclusion Criteria for Step 3:

• Currently enrolled in Step 1
• Undetectable HCV RNA or a 2-log or greater decrease in plasma/serum HCV viral load.
• On Step 1 study treatment for no longer than 18 weeks

Exclusion Criteria for Steps 1 and 3:

• Have received HCV treatment within 4 weeks of study entry. Participants currently receiving treatment for HCV, if non-EVRs, were considered for direct entry into Step 2, without the run-in period in Step 1.
• Could not tolerate treatment with PEG-IFN, defined as missing 3 or more consecutive PEG-IFN doses during the first 12 weeks or a total of 5 doses prior to Step 3 entry. Participants who have missed doses of ribavirin will not be excluded from Step 3 entry.
• Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days prior to study entry
• Alpha feto protein level 400 ng/ml or greater within 24 weeks prior to study entry, or alpha feto protein level greater than 50 ng/ml and less than 400 ng/ml (unless computed tomography [CT] scan or magnetic resonance imaging [MRI] shows no evidence of hepatic tumor) within 24 weeks prior to study entry
• Decompensated liver disease, including presence or history of ascites, variceal bleeding, and brain or nervous system damage as a result of liver damage
• Other causes of significant liver disease, including hepatitis A or B, excess iron deposits in the liver (hemochromatosis), or homozygote alpha-1 antitrypsin deficiency
• Use of systemic corticosteroids, interferon gamma, TNF-alpha inhibitors, rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir, or hydroxyurea within 2 weeks prior to study entry
• Known allergy/sensitivity to PEG-IFN alfa-2a or ribavirin or their formulations
• History of uncontrolled seizure disorders
• Clinically active thyroid disease. Thyroid hormone replacement therapy is permitted, but thyroid-stimulating hormone (TSH) and free thyroxine index (FTI) must be in normal range.
• History of autoimmune processes, including Crohn's disease, ulcerative colitis, severe psoriasis, and rheumatoid arthritis, that may be made worse by interferon use
• Any systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry
• Malignancy
• Active coronary artery disease within 24 weeks prior to study entry
• Acute or active AIDS-defining opportunistic infections within 12 weeks of study entry
• Hemoglobin abnormalities (e.g., thalassemia) or any other cause of or tendency to break down red blood cells (hemolysis)
• History of major organ transplantation with an existing functio