Peginterferon Alpha-2a and Ribavirin to Treat Hepatitis C in HIV-infected Patients

Phase 2

Completed

Conditions: Hepatitis C
HIV Infections

Interventions: Drug: standard dose pegylated interferon alfa -2a and ribavirin
Drug: Double dose pegylated interferon with weight based Ribavirin

Registration Number: NCT00085917

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Peginterferon alpha-2a is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2a. This compound stays in the blood longer than unmodified interferon alpha-2a, causing a higher blood concentration and thus maintaining greater activity against the hepatitis C virus.

HIV-infected patients 18 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 are screened with a medical history and physical examination, blood and urine tests, eye examination, chest x-ray, electrocardiogram (EKG), liver ultrasound, and pregnancy test in women who are able to become pregnant. If a recent liver biopsy is not available, this test is done to determine the type and severity of liver disease. The patient is given a sedative before the procedure. Then, 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.

Participants begin treatment with injections under the skin of peginterferon alpha-2a and ribavirin pills by mouth on study day 0. Peginterferon is given either once or twice a week for 4 weeks and then once a week for 44 weeks. Ribavirin is given daily. In addition, patients continue to take all other medications prescribed by their doctor. Clinic visits are scheduled for the following procedures:

* Days 1, 3, 4, 7, 10 and weeks 2, 3, and 4 - Blood tests for safety measures and to measure blood levels of HIV and HCV.

* Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection. In addition, eye examinations are done every 3 months, and pregnancy and thyroid function tests are done several times during the treatment period.

* Week 48 or end of treatment - Treatment stops after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients return to the clinic for a chest x-ray, EKG, blood tests, and abdominal ultrasound. Patients are hospitalized for a repeat liver biopsy.

* Weeks 52, 56, 64 and 72 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection, and a urine pregnancy test in women.

Detailed Description: Hepatitis C infection occurs in one-third of all HIV-infected individuals. Liver disease has become more significant among patients coinfected with HIV and HCV. Several studies have shown that coinfected individuals develop earlier and more severe liver disease. Pegylated interferon alpha with ribavirin has become the therapy of choice among people with HCV alone. This is a randomized controlled study to address the safety and efficacy of a 4 week induction therapy consisting of twice-weekly pegylated interferon alpha-2a and daily ribavirin on HIV-1 and hepatitis C coinfected individuals. Twenty-two patients who are infected with both HIV and HCV and who also have evidence of chronic hepatitis will be randomized to receive peginterferon alpha-2a either twice weekly or once weekly for four weeks. They will then continue with standard weekly peginterferon for 44 more weeks. The patients will receive standard daily dose of ribavirin during the entire 48 weeks. These patients will be monitored for peginterferon level, HCV viral load, HIV viral load and CD4 counts and undergo a baseline liver biopsy and another at the end of 72 weeks. The results of the study will enable us to better delineate the efficacy of twice weekly peginterferon induction therapy in suppressing the hepatitis C virus in the first 4 weeks of the therapy. Since viral suppression for hepatitis C in the early phase of the combination treatment has predictive values for long term eradication of the virus, a therapy that improves early viral suppression may improve the long term cure rate. This will be especially important given the current low cure rate of HCV among HIV coinfected individuals.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard dose arm	standard dose pegylated interferon alfa -2a and ribavirin	Pegylated interferon alfa -2a STANDARD DOSE Pegasys 180ug/week
Double dose arm	Double dose pegylated interferon with weight based Ribavirin	Double dose pegylated interferon with weight based Ribavirin

Primary Outcome Measures

Name	Time	Method
Number of Participants With Sustained Virologic Response (SVR)	72 weeks	SVR \[ Sustained virological response\] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Normalization of Liver Enzymes	week 24, week 48, week 72	normalization of liver enzymes :Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) Alanine aminotransferase (ALT): Normal 6 - 41 U/L Aspartate aminotransferase (AST) : Normal 9 - 34 U/L
Number of Participants With Adverse Events	48 weeks	Adverse Events - Anemia, Neutropenia and Psychiatric adverse events