The Impact of HAART on Response to Hepatitis C Treatment in Patients Taking Peginterferon Alpha-2b and Ribavirin
This study will evaluate how controlling HIV infection with HAART (highly active antiretroviral therapy) affects the response to hepatitis C treatment with peginterferon alpha-2b and ribavirin in HIV-infected patients with chronic hepatitis C. HIV worsens liver disease caused by hepatitis C. Since treatment of HIV infection with HAART improves immune function, it may be beneficial to start HAART before treating HCV.
HIV-infected patients 18 years of age and older with chronic hepatitis C infection may be eligible for this study. Patients must have an HCV viral load greater than 2000 copies/mL and a CD4 count that is either more than 500 cells/mm3, or more than 350 cells/mm3 with an HIV viral load no greater than 40,000 particles/mL. Candidates will be screened for current or previous diseases, conditions or treatments that may exclude them from this study. Screening includes a medical history and physical examination, eye examination, blood and urine tests, chest X-ray, electrocardiogram (EKG), liver ultrasound, and, possibly, a liver biopsy, if a recent one is not available. The liver biopsy is optional and is done to determine the severity of liver disease. Patients will be sedated for this test. 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. Patients remain in the hospital overnight for monitoring. Women of childbearing age will have a pregnancy test.
Patients enrolled in the study will be randomly assigned to one of the following treatment groups: 1) pegylated interferon and ribavirin for 48 weeks (control group); or 2) HAART for 6 months, followed by 48 weeks of pegylated interferon and ribavirin.
HAART group - Patients taking HAART will be followed in the clinic every 2 weeks for the first month and then monthly for the next 5 months. After 6 months of HAART they will begin taking pegylated interferon and ribavirin and will follow the dosing and follow-up schedule outlined below for patients in the control group.
Control group - Patients will have weekly injections under the skin of peginterferon alpha-2b and ribavirin pills daily by mouth. Clinic visits will be scheduled as follows:
- Days 1, 3, 7, and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. HCV medications will be injected on days 7 and 21.
- 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 pegylated interferon and ribavirin treatment and its effect on the HCV infection. Eye examinations will be done every 3 months.
- Week 48 or end of treatment - Treatment with pegylated interferon and ribavirin will stop after 48 weeks. At this time (or earlier for those who do not complete the 48 weeks of treatment), patients will return to the clinic for a routine visit, blood tests (including a test for hepatitis B) and abdominal ultrasound. Patients may also be hospitalized for 2 days for a repeat optional liver biopsy.
- Week 72 and extended follow-up visits - At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination.
Drug: highly active antiretroviral therapy (HAART)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||A Randomized, Controlled Study to Assess the Impact of Highly Active Antiretroviral Therapy to Hepatitis C Therapy in Patients Coinfected With HIV-1 and Treated With Peginterferon Alpha-2b and Ribavirin|
|Study Start Date:||February 2002|
|Estimated Study Completion Date:||April 2004|
Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) has risen dramatically since the explosion of the HIV pandemic twenty years ago, with one third of all HIV positive persons also infected with HCV. Numerous studies have suggested that HIV exacerbates several steps in the natural history of hepatitis C, and as survival among HIV-infected patients increases, hepatitis C-related morbidity and mortality is expected to follow a similar trend in coinfected patients. Some investigators advocate the initiation of highly active antiretroviral therapy (HAART) for this population prior to the initiation of HCV therapy. It is postulated that HAART will improve the host immune function by increasing the CD4+ cell count and decreasing HIV viral load, thought to be advantageous for patients starting HCV therapy. Despite its promising hypothesis, whether HAART ultimately leads to a reduction in HCV load in coinfected persons remains controversial. This is a non-blinded, randomized controlled trial to evaluate the impact of HAART on the immunologic, virologic, and clinical responses to HCV treatment with peginterferon and ribavirin in coinfected individuals with CD4 greater than or equal to 500 cells/mm (3) or greater than or equal to 350 cells/mm(3) and a viral load less than or equal to 40,000 copies/mL. The study will also address the safety and efficacy of administering a combination of HAART along with peginterferon alpha-2b and ribavirin to HIV-infected individuals. 128 patients who are coinfected with HIV and HCV will be recruited for the study and randomized to receive one of two treatment regimens: 1) control group: will be treated with peginterferon alpha-2b and ribavirin for 48 weeks, or 2) experimental group: will be treated with highly active antiretroviral therapy for six months. At that point, they will begin receiving peginterferon alpha-2b and ribavirin at the same doses as the control group for 48 weeks. During the 72-week follow up period, these patients will be monitored for both HCV and HIV viral loads and CD4+ lymphocyte counts. The results of the study will enable us to better delineate the relationship between the immune reconstitution effects induced by HAART and the clinical, immunologic, and virologic responses of coinfected persons treated with peginterferon and ribavirin. In addition, evaluating the safety of coadministering peginterferon, ribavirin, and HAART will further refine the best therapeutic regimen for this patient population.
|United States, Maryland|
|National Institute of Allergy and Infectious Diseases (NIAID)|
|Bethesda, Maryland, United States, 20892|