The Impact of HAART on Response to Hepatitis C Treatment in Patients Taking Peginterferon Alpha-2b and Ribavirin

INCLUSION CRITERIA: Age greater than or equal to 18 years Documentation of HIV-1 infection by a licensed ELISA test and confirmed by a Western Blot CD4 greater than or equal to 500 cells/mm(3) or CD4 greater than or equal to 350 cells/mm(3) and HIV VL less than or equal to 40,000 copies per milliliter CD4 nadir not below 200 cells/mm(3) If not HAART naive, history of HIV VL suppression while on HAART treatment. Patients who are currently on HAART but do not meet criteria for the initiation of HAART according to current DHHS guidelines must be willing to come off their regimen 3 months prior to study initiation. Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody. HCV RNA level greater than 2000 copies per milliliter by polymerase chain reaction Patients naive to HCV treatment at time of enrollment. Serum creatinine less than or equal to 1.5 mg/dL Serum phosphorus greater than or equal to 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL) Neutrophil count greater than or equal to 1000 cells/mm(3) Platelets greater than or equal to 75,000/mm(3) Hemoglobin greater than or equal to 8.0 mg/dL ALT less than 7 X the NIH upper limit of normal Not pregnant or breast-feeding. Pregnancy tests must be negative within two weeks prior to dosing with study medications. Due to the teratogenic effects of ribavirin, for women of child-bearing age, the use of effective contraception during the study will be required. These include abstinence, surgical sterilization of either partner, barrier methods such as a diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter the metabolism of hormonal contraception. Patients must have a primary MD responsible for their HIV infection and liver disease. Willing to designate a person for durable power of attorney on NIH form for medical research and medical care purposes at the NIH Clinical Center. Ability to learn how to safely inject medication subcutaneously or have a family member, relative or partner who is willing to learn to inject study medication. Competency to sign informed consent and willingness to comply with study requirements and clinic policies. Willingness to have blood and tissue specimens stored in NIH facilities. Child-Pugh score less than 6. Willingness for female patients to practice at least two reliable forms of effective contraception during treatment with ribavirin. Effective means of contraception include barrier and hormonal methods. Willingness for male patients to practice effective contraception during treatment with ribavirin, including barrier methods. EXCLUSION CRITERIA: PT-INR (in the absence of anti-cardiolipin Ab) by greater than or equal to 2. Organ transplant recipient Recent HIV seroconverters (must be 6 months or more with documented HIV diagnosis). Patients who are medically indicated to begin HAART therapy Elevated alpha-fetoprotein level (greater than or equal to 100 ng/mL). Coexisting neoplastic disease requiring cytotoxic therapy. Have had cancer other than Kaposi's sarcoma of the skin, other skin cancers treated by resection, Bowen's disease, or localized cervical or anal cancer in the 5 years prior to enrollment Have had significant renal dysfunction within the previous 12 months or evidence of significant protein wasting Severe cardiac or pulmonary decompensation as assessed by the PI. Severe liver decompensation or advanced cirrhosis patients Severe psychiatric disorder that would interfere with the adherence to protocol requirements. Autoimmune disorders including inflammatory bowel diseases, and optic neuritis as assessed by the PI. Uncontrolled seizure disorder Severe retinopathy. Direct bilirubin more than or equal to 2 times ULN. No patients using long-term systemic corticosteroids, immunosuppressives, IL-2, or cytotoxic agents within 60 days of enrollment. Active systemic infections (other than hepatitis C and HIV). Liver disease caused by reasons other than hepatitis C like HBV, HDV, Wilson's hemochromatosis, or autoimmune hepatitis (ANA greater than or equal to 3.0) except history of drug-associated hepatitis with discontinuation of the causative agent. Hepatic mass suggestive of hepatocellular carcinoma. Current alcohol or substance use. 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, chronic nausea, or vomiting Any pre-existing hemoglobinopathy. Patients taking any of the following medications: rifampin/rifampicin, rifabutin, pyrazinamide, isoniazid, ganciclovir, thalidomide, oxymetholone, immunomodulatory treatments (including supraphysiologic doses of steroids and radiation, and antineoplastic agents). Patients taking any investigational drugs and herbal remedies, and other complementary/alternative medications for possible or perceived effects against HCV. Patients cannot be receiving IL-2 during participation in this study. Ribavirin is contraindicated in male partners of women who are pregnant. Therefore, potential male patients with pregnant female partners will be excluded.