Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients (HEPCPR)
This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2b and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. In studies of patients with hepatitis C alone, interferon alpha-2b plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alpha-2b is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2b. This compound stays in the blood longer than unmodified interferon alpha-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 alpha-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.
Drug: Peginterferon alpha-2b
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Non-Randomized, Open Label, Study to Assess Hepatitis C Viral Kinetics in Predicting the Clinical Response in Patients With Hepatitis C Infection Coinfected With HIV-1 Treated With Peginterferon Alpha-2b and Ribavirin|
- Correlation of HCV viral kinetics to treatment response rates. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Gene an proteomics expression in PBMC and liver and their relationship to the treatment response rates. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||June 2001|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Drug: Peginterferon alpha-2b
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.
Hepatitis C infection occurs in one-third of all HIV-infected individuals. Liver disease has become more clinically significant among patients coinfected with HIV and HCV. Several studies have shown that coinfected individuals develop earlier and severe liver disease. Interferon with ribavirin has become the therapy of choice among people with non-genotype 1a. This is a pilot study to address the relationship of clinical response to combination therapy to the virologic and immunologic parameters. The study will also address the safety and efficacy of the peginterferon alpha-2b among HIV- infected individuals. The predictive ability of baseline HCV viral load, rate of decline of HCV viral load, HIV viral load and CD4 counts to the clinical response of chronic hepatitis to peginterferon and ribavirin will also be studied. Approximately sixty patients who are infected with both HIV and HCV and also have evidence of fibrosis will receive peginterferon alpha-2b and ribavirin for 48 weeks. In order to enroll sixty patients for this study, we will be screening a total of 180 patients. During the 72 weeks study these patients will be monitored for HCV viral load, and other HIV viral load and CD4 counts. Viral kinetics will also be monitored closely and the slope of second, slower phase decline of HCV viral load, which corresponds to the rate of infected cell death presumably may lead to sustained hepatitis C virologic response. The results of the study will enable us to better delineate the possible predictors of sustained response to peginterferon and ribavirin. The safety and tolerability of a combination therapy with peginterferon and ribavirin among HIV-infected individuals on antiretroviral therapy will further define the standard therapy of chronic hepatitis C in HIV-infected individuals.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|