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

• Status: Completed
• Trial end date: 2009-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Interferons; Peginterferon alfa-2a; Ribavirin

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