Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients
This study will evaluate the safety and effectiveness of adding the experimental drug adefovir dipivoxil to lamivudine for treating hepatitis B virus (HBV) infection in HIV-infected patients with liver cirrhosis. Adefovir inhibits HBV by interfering with replication of the virus's genetic material. In some people, the drug has been active against strains of HBV that are resistant to lamivudine; it may also have some activity against HIV.
HIV-infected patients 21 years of age and older with chronic hepatitis B infection and liver cirrhosis who have received lamivudine treatment for at least 1 year may be eligible for this 48-week study. Candidates will be screened with a complete medical history, blood tests and a 24-hour urine collection. Blood tests include HLA typing (a test of genetic markers on white blood cells that permit specialized immunology studies). Within 4 weeks, candidates who appear eligible for the study will have a physical examination and medical history, an abdominal ultrasound (imaging test using sound waves) to check for cancer of the liver, chest X-ray and electrocardiogram (EKG). Blood and urine tests will also be done, and women who can become pregnant will have a pregnancy test.
Patients who meet the study criteria and decide to participate will then start treatment with one 10-mg adefovir pill per day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Follow-up clinic visits will be scheduled as follows:
- Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for specialized immunology tests and to measure blood levels of HIV and HBV.
- Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine (single sample) tests will be done to determine the side effects of adefovir and its effect on the HBV infection.
- Week 48 or early termination (end of study) - Blood tests (including tests for hepatitis C and D), abdominal ultrasound and a 24-hour urine collection to evaluate kidney function will be done.
- Monthly visits beyond week 48 - Based on the HBV response to treatment and the availability of the drug from the sponsor, patients may be offered to extend their treatment with adefovir. Those who continue will have monthly follow-up visits for blood and urine (single sample) tests.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||Adefovir Dipivoxil for the Treatment of Hepatitis B in Human Immunodeficiency Virus Infected Patients With Decompensated Hepatitis B Liver Disease and a Hepatitis B Viral Load of at Least 1.0 X 10(6) (Copies/mL) Despite 52 Weeks of Lamivudine Therapy|
|Study Start Date:||March 2001|
|Estimated Study Completion Date:||February 2004|
Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who have advanced liver disease (decompensated cirrhosis by Child-Pugh score and no known cause of hepatitis other than HBV), a HBV viral load of at least 1 million copies/mL blood, and at least one year of therapy with lamivudine will be treated with open-label adefovir dipivoxil 10 mg daily and lamivudine 150 mg bid to evaluate the safety and efficacy of this regimen in this patient group and to obtain specimens for studies of immune responses to HBV in HIV-infected patients. Additionally the kinetics of viral load response to adefovir will be assessed. Specimens will be stored for possible use in evaluating HBV and HIV resistance to adefovir. L-carnitine supplementation will be used only if low serum carnitine levels are documented. Patients will be followed for HBV viral load response to adefovir for 48 weeks with possible extension. The primary study endpoints will be HBV viral load at week 24 (per-protocol patients) and DAVG at week 24 (intent-to-treat patients). Adefovir will be discontinued for toxicity; there will be no dose reduction. Up to 30 subjects will be enrolled.
|United States, Maryland|
|National Institute of Allergy and Infectious Diseases (NIAID)|
|Bethesda, Maryland, United States, 20892|