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Treatment of Hepatitis in Patients Who Are Triple-Infected With HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV)
This study has been terminated.
First Received: January 3, 2003   Last Updated: August 5, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00051077
  Purpose

This study will investigate the safety and effectiveness of using adefovir dipivoxil (ADV), pegylated interferon (PEG-INF), and ribavirin (RBV) in patients triple-infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. Patients in this study must be taking lamivudine (3TC).


Condition Intervention Phase
HIV Infections
Hepatitis B
Hepatitis C
Drug: Adefovir dipivoxil
Drug: Peginterferon-alfa-2A
Drug: Ribavirin
Procedure: Liver Biopsy
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Safety/Efficacy Study
Official Title: A Phase II Study of Adefovir Dipivoxil, Pegylated Interferon Alfa-2A, and Ribavirin Treatment in HBV and HCV Infected Subjects With HIV Disease

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 110
Detailed Description:

The emergence of liver disease in HIV infected patients with coinfections of HBV and/or HCV has become increasingly important in disease progression in the post-HAART (highly active antiretroviral therapy) era. The overall rate of HBV and HCV infection in HIV infected persons is 5% to 10%. There is convincing evidence that HIV infection exacerbates the severity of viral hepatitis and the progression of liver disease. Hepatitis treatment studies have generally excluded HIV patients with both HBV and HCV. As such, the influence of HBV on HCV treatment in HIV infected patients is unknown. This study will investigate the safety and anti-HBV efficacy of ADV + PEG-INF + RBV triple therapy in patients with HCV, HIV, and 3TC-resistant HBV. The study will also evaluate the effect of HBV and HBV therapy on HCV and HIV disease progression.

Patients with documented HIV, 3TC-resistant HBV, and HCV will be randomized to one of two treatment regimens for 48 weeks. Patients in both groups will receive daily oral RBV and weekly subcutaneous injections of PEG-INF. Patients in Group A will receive daily ADV; patients in Group B will receive placebo. After 48 weeks of study treatment, all study medications will be discontinued and patients will undergo liver biopsy. Patients will then be followed for an additional 24 weeks. Throughout the study, investigators will monitor numerous lab values and patients will be asked to complete multiple adherence questionnaires. Subjects who have a confirmed 2 point increase in Child-Pugh-Turcotte liver disease prognosis score at any time during the study will permanently discontinue PEG-INF and RBV and register to Step 2 to receive open label ADV.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • HIV positive
  • Documented HCV viremia within 48 weeks prior to study entry
  • HBV DNA >= 500,000 copies/ml within 12 weeks prior to study entry
  • Chronic viral liver disease as documented by liver biopsy within 52 weeks prior to study entry
  • Treated with 3TC for at least 26 weeks prior to study entry
  • CD4+ count >200 cells/mm3 within 35 days prior to study entry
  • HIV-1 viral load of <55,000 copies/ml within 35 days prior to entry
  • Either have been on stable antiretroviral therapy for at least 12 weeks prior to study entry and plan to remain on same antiretroviral therapy OR have not received any antiretroviral therapy in the 12 weeks prior to the study and do not plan to begin antiretroviral therapy during the first 12 weeks of the study
  • Acceptable methods of contraception

Exclusion Criteria

  • History of any medical condition associated with chronic liver disease other than viral hepatitis
  • History of ALT elevations over 3 X baseline level
  • Child-Pugh-Turcotte (CPT) score > 5
  • Previous suicide attempt or hospitalization for psychiatric illness within 2 years prior to study entry
  • History of hypersensitivity to RBV, interferon, or other components of study medications
  • Uncontrolled seizure disorder
  • Certain medical conditions, including hepatitis D, autoimmune disorders, Chronic Obstructive Pulmonary Disease, cardiac disease, cancer, hemoglobinopathy, major organ transplant, kidney disease, opportunistic infection, and retinopathy
  • Certain medications
  • Pregnancy or breast-feeding
  • Male partners of women who are pregnant
  • Active drug or alcohol use or dependence
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00051077

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35924-2050
United States, California
San Francisco General Hosp
San Francisco, California, United States, 94110
United States, Colorado
Univ of Colorado Health Sciences Center, Denver
Denver, Colorado, United States, 80262-3706
United States, New York
Beth Israel Med Ctr
New York, New York, United States, 10003
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 45267-0405
United States, Texas
Univ of Texas, Galveston
Galveston, Texas, United States, 77555-0435
Univ of Texas, Southwestern Med Ctr
Dallas, Texas, United States, 75235-9173
Sponsors and Collaborators
Investigators
Study Chair: Dickens Theodore, M.D., Ph.D. The University of North Carolina, Chapel Hill
Study Chair: Kenneth E Sherman, M.D., Ph.D University of Cincinnati
  More Information

Additional Information:
Publications:
Study ID Numbers: ACTG A5149
Study First Received: January 3, 2003
Last Updated: August 5, 2008
ClinicalTrials.gov Identifier: NCT00051077     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Infections
Hepatitis B
Hepatitis C
Interferon Alfa-2a
Adefovir dipivoxil
Ribavirin
Antiviral Agents
Drug Resistance, Viral
Treatment Experienced

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Communicable Diseases
Sexually Transmitted Diseases, Viral
Liver Diseases
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Flaviviridae Infections
Antineoplastic Agents
Physiological Effects of Drugs
Ribavirin
Hepatitis, Viral, Human
Infection
Hepadnaviridae Infections
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Hepatitis B
Growth Inhibitors
Angiogenesis Modulating Agents
Hepatitis C
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Interferon-alpha
RNA Virus Infections
Immune System Diseases
Growth Substances
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 09, 2009