PIFNPKA Randomized Controlled Trial to Evaluate the Safety and Efficacy of Twice-Weekly Peginterferon Alpha 2a and Ribavirin Induction Therapy for Chronic Hepatitis C in Patients Who Are Coinfected With HIV-1

Fecha de inicio: 1 de junio de 2004

INCLUSION CRITERIA * Age greater than or equal to18 years. * Documentation of HIV-1 infection by licensed ELISA test and confirmed by a Western Blot. * Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody and on HCV RNA level of 2000 or greater. * Histopathologic features consistent with chronic hepatitis C on liver biopsy at the time of enrollment. A liver biopsy done for a subject within a year prior to his or her participation may be used as the baseline biopsy. * Patients with CD4+ cell count greater than 200 cells/mm3 or CD4+ cell percentage greater than 14%. * Ability to sign informed consent and willingness to comply with the study requirements and clinic policies. * Serum phosphorus greater than or equal to 2.2 mg/dL and less than or equal to 4.4 (normal range NIH 2.3-4.3 mg/dL). * Neutrophil count greater than or equal to 1000 cells/mm3. * Platelets greater than or equal to 50,000/ mm3. * Hemoglobin greater than or equal to 10.5 mg/dL. * ALT less than 7 X the NIH upper limit of normal. * Serum lipase less than 1.5 X the NIH upper limit of normal. * Not pregnant or breast-feeding. Pregnancy test must be negative within two weeks prior to dosing with study medications. * If the patient is able to become pregnant then she must use two effective methods of contraception during the study. Effective contraceptive methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter metabolism of hormonal contraception. This is advised on the basis of using ribavirin, which may have a potential teratogenic effect in pregnant women. * Need to have a primary doctor outside of OP8 or as part of the OP8 training clinic who will be taking care of the patients for their HIV infection and liver disease. * Willing to designate a person for durable power of attorney on the NIH form for medical research and medical care purposes at the NIH Clinical Center. * Able to learn to safely inject medication subcutaneously or be able to find another person or a clinic to inject for him/her. EXCLUSION CRITERIA * Patient should not be on other experimental therapies during their participation in this protocol. * Patients should not have used interferon or peginterferon previously for the treatment of hepatitis C * Liver histology which, in the opinion of Clinical center pathologist, is consistent with any other co-existent cause of chronic liver disease as defined as chronic hepatitis B with positive HBSag, autoimmune hepatitis with a positive ANA greater than 1 unit or positive anti mitochondrial antibody greater than 1 unit, cholestatic disease with persistent elevation of Alkaline phosphatase, primary biliary cirrhosis or sclerosing cholangitis, Wilson's disease, alpha-1-antitrypsin deficiency, steatohepatitis (alcohol or non alcoholic) with marked steatosis, many Mallory bodies, or extensive zone 3 periportal fibrosis. * Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC X 100%) of greater than 50% and (2) presence of 3+ or more stainable Iron on liver biopsy according to the study pathologist or a history of previous phlebotomy for Iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. Those who have compound heterozygosity to C282Y and H63D are also not eligible. * Child Turcotte Pugh score greater than 7. * PT-INR greater than 2 or history of hemophilia. * Organ transplant recipient. * Creatinine clearance less than 50 mL/min. * Elevated alpha-fetoprotein level (greater than 100 ng/mL). * Coexisting neoplastic disease except for Kaposi's Sarcoma, any non-metastatic skin cancer that has been resected, non-metastatic cervical or anal cancer that has been resected. * Severe cardiac or pulmonary decompensation. * Severe psychiatric disorder that would interfere with the adherence to protocol requirements. * Preexisting autoimmune disorders including inflammatory bowel diseases, psoriasis, and optic neuritis. * Preexisting uncontrolled seizure disorder. * Preexisting pancreatitis. * Severe retinopathy as determined by the ophthalmologist. * Hemoglobinopathy. * Currently taking didanosine as part of antiretroviral regimen. * Direct bilirubin greater than 0.6 mg/dL. * Using long-term systemic corticosteroids, immunosuppressives, or cytotoxic agents within 60 days of enrollment into the trial. * Chronic viral hepatitis of any other etiology other than hepatitis C. * Active systemic infections other than hepatitis C and HIV. * Liver disease caused by reasons other than hepatitis C like HBV, HDV, Wilson's, hemochromatosis, autoimmune hepatitis (ANA greater than 1 unit) except history of drug-associated hepatitis with discontinuation of the causative agent. * Hepatic mass suggestive of hepatocellular carcinoma as detected by ultrasound scan. * Alcohol or substance abuse that potentially could interfere with patient compliance. * History of esophageal varices. * Any systemic illness that will make it unlikely that the subject will be able to return to NIH for the required study visits. * Evidence of gastrointestinal malabsorption or chronic nausea or vomiting. * Male partners of pregnant women. * Pregnant women. * Breastfeeding women.