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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.

Sponsored by: 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

MedlinePlus related topics:   AIDS    Hepatitis    Hepatitis B    Hepatitis C   

ChemIDplus related topics:   Ribavirin    Peginterferon Alfa-2a    Hepatitis B Vaccines    Interferon alfa-n1    Interferon alfa-2a    Interferon alfa-2b    Interferons    Adefovir dipivoxil    Adefovir   

U.S. FDA Resources

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

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.     University of North Carolina    
Study Chair:     Kenneth E Sherman, M.D., Ph.D     University of Cincinnati    
  More Information

Click here for more information about Peginterferon-alfa-2A (PEG-INF).  This link exits the ClinicalTrials.gov site
 
Click here for more information about Ribavirin (RBV).  This link exits the ClinicalTrials.gov site
 
Click here for more information about Lamivudine (3TC).  This link exits the ClinicalTrials.gov site
 
Haga clic aquí para ver información sobre este ensayo clínico en español.  This link exits the ClinicalTrials.gov site
 

Publications:

Study ID Numbers:   ACTG A5149
First Received:   January 3, 2003
Last Updated:   August 5, 2008
ClinicalTrials.gov Identifier:   NCT00051077
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

Study placed in the following topic categories:
Interferon-alpha
Sexually Transmitted Diseases, Viral
Liver Diseases
Interferons
Ribavirin
Acquired Immunodeficiency Syndrome
Hepatitis, Viral, Human
Immunologic Deficiency Syndromes
Hepatitis
Virus Diseases
Digestive System Diseases
HIV Infections
Sexually Transmitted Diseases
Hepatitis B
Peginterferon alfa-2a
Adefovir dipivoxil
DNA Virus Infections
Hepatitis C
Interferon Alfa-2a
Adefovir
Interferon Alfa-2b
Retroviridae Infections

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Flaviviridae Infections
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Infection
Angiogenesis Inhibitors
Hepadnaviridae Infections
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Growth Inhibitors
Angiogenesis Modulating Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 28, 2008




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