Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV)
HIV Infections, Hepatitis C, Liver Disease
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring Treatment Experienced
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
Sites / Locations
- Alabama Therapeutics CRS
- University of Southern California CRS
- UCLA CARE Center CRS
- Stanford AIDS Clinical Trials Unit CRS
- UCSD Antiviral Research Center CRS
- Ucsf Hiv/Aids Crs
- Santa Clara Valley Med. Ctr.
- University of Colorado Hospital CRS
- Georgetown University CRS (GU CRS)
- Univ. of Hawaii at Manoa, Leahi Hosp.
- Northwestern University CRS
- Indiana Univ. School of Medicine, Infectious Disease Research Clinic
- Indiana Univ. School of Medicine, Wishard Memorial
- Johns Hopkins University CRS
- Massachusetts General Hospital CRS (MGH CRS)
- Brigham and Women's Hosp. ACTG CRS
- Beth Israel Deaconess Med. Ctr., ACTG CRS
- Washington University Therapeutics (WT) CRS
- Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
- Beth Israel Med. Ctr., ACTU
- Weill Cornell Chelsea CRS
- NY Univ. HIV/AIDS CRS
- Weill Cornell Uptown CRS
- Columbia P&S CRS
- Trillium Health ACTG CRS
- McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit
- Univ. of Rochester ACTG CRS
- Chapel Hill CRS
- Cincinnati CRS
- MetroHealth CRS
- Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
- University of Pittsburgh CRS
- The Miriam Hospital Clinical Research Site (TMH CRS) CRS
- Vanderbilt Therapeutics (VT) CRS
- Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic
- Univ. of Texas Medical Branch, ACTU
- Puerto Rico AIDS Clinical Trials Unit CRS
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Arm A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)
Arm B: OL (PEG-IFN, RBV) then OL Randomized (Observation)
Arm C: OL (PEG-IFN, RBV) then OL (PEG-IFN, RBV)
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.