Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients
Condition: Hepatitis C; HIV Infections
MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis
Intervention: Peginterferon alfa-2b; Ribavirin
Intervention description: Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously; Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks.
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2b; Interferon-alpha
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liver Disease; Virologic Response; Immune Mechanisms; Cirrhosis; Eradication; HIV; Hepatitis C

Summary:

      This study will evaluate the safety and effectiveness of combination therapy with
      peginterferon alfa-2b and ribavirin for treating hepatitis C virus (HCV) infection in
      HIV-infected patients. In studies of patients with hepatitis C alone, interferon alfa-2b plus
      ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alfa-2b is
      a compound that results from attaching a polyethylene glycol molecule to interferon alfa-2b.
      This compound stays in the blood longer than unmodified interferon alfa-2b, causing a higher
      blood concentration and thus maintaining activity against the hepatitis C virus.

      HIV-infected patients 21 years of age and older with chronic hepatitis C infection and a
      viral load greater than 2000 copies/mL may be eligible for this 2 1/2-year study. Candidates
      will be screened with blood and urine tests and possibly a liver biopsy, if a recent one is
      not available. The liver biopsy is done to determine the severity of liver disease. For this
      test, patients are admitted to the NIH Clinical Center for 1 to 2 days. A sedative is
      injected into an arm vein, the skin in the area over the biopsy site is numbed with a local
      anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small
      tissue sample. The patient remains in the hospital overnight for monitoring. A chest X-ray,
      electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks of the screening
      tests, candidates who appear eligible for the study will have a physical examination, medical
      history and repeat blood tests. Women who can become pregnant will have serial pregnancy
      tests throughout the study.

      Patients who meet the study criteria and decide to participate will begin treatment with
      weekly injections under the skin of peginterferon alfa-2b and take ribavirin pills twice a
      day by mouth. In addition, patients will continue to take all other medications prescribed by
      their doctor. Clinic visits will be scheduled as follows:

        -  Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood
           levels of HIV and HCV.

        -  Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56 and 64 - Blood and urine tests
           will be done to determine the side effects of treatment and its effect on the HCV
           infection.

        -  Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or
           earlier for those who do not complete the 48 weeks, patients will return to the clinic
           for a routine test.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Age greater than or equal to 18 years.

        Documentation of HIV-1 infection by any licensed ELISA test and confirmed by a Western
        Blot.

        Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C
        antibody.

        HCV RNA level greater than 2000 IU/ml by bDNA.

        Infected with HCV genotype 1.

        Histopathologic features consistent with chronic hepatitis C on liver biopsy at the time of
        enrollment.

        Patients with CD4 greater than 300 cells/mm(3).

        Ability to sign informed consent and willingness to comply with the study requirements and
        clinic policies.

        Serum creatinine less than 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 times the NIH upper limit of normal.

        Serum lipase less than 1.5 times 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 capable of pregnancy: use of effective contraception during study: effective
        contraception 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 OP8 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.

        Ability to learn how to safely inject medication subcutaneously.

        EXCLUSION CRITERIA:

        PT-INR (in the absence of anti-cardiolipin antibody) prolonged by greater than 2 seconds.

        Organ transplant recipient.

        Elevated alpha-fetoprotein level (greater than 100 ng/mL).

        Coexisting neoplastic disease requiring cytotoxic therapy.

        Child Pugh's class B.

        Severe cardiac or pulmonary decompensation.

        Severe liver decompensation or advanced cirrhosis patients.

        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.

        Severe retinopathy.

        Hemoglobinopathy

        Direct bilirubin more than or equal to 2 times ULN.

        No patients 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 160) except history of
        drug-associated hepatitis with discontinuation of the causative agent.

        Hepatic mass suggestive of hepatocellular carcinoma.

        Current alcohol or substance abuse that potentially could interfere with patient
        compliance.

        Significant heart failure.

        Evidence 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.

        Currently taking didanosine (ddl or Videx-EC or Videx) as part of antiretroviral regimen.