Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV)
Condition: HIV Infections; Hepatitis C; Liver Disease
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Liver Diseases
Intervention: Peginterferon alfa-2a; Ribavirin
Intervention description: 180 mcg PEG-IFN subcutaneously; One tablet or capsule containing ribavirin 200 mg
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 333.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Treatment Experienced

Summary:

      Infection with both HIV and hepatitis C virus (HCV) may result in serious and sometimes fatal
      liver disease. The purpose of this study was to test the effectiveness of long-term pegylated
      interferon alfa-2a (PEG-IFN) and ribavirin treatment in slowing liver disease progression in
      people infected with both HIV and HCV.
    

Eligibility criteria:

        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 functional graft

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with study adherence

          -  Uncontrolled or active depression or other psychiatric disorder, such as untreated
             Grade 3 psychiatric disorder, medically untreatable Grade 3 disorder, or any
             hospitalization within 52 weeks of study entry that, in the opinion of the
             investigator, may interfere with study requirements

          -  Other serious illness or chronic medical condition that, in the opinion of the
             investigator, may have prevented participant's completion of the study

          -  Pregnant or breastfeeding