Treatment of Hepatitis in Patients Who Are Triple-Infected With HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV)

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ClinicalTrials.gov Identifier: NCT00051077

Recruitment Status : Withdrawn

First Posted : January 6, 2003

Last Update Posted : May 18, 2012

Sponsor:

Information provided by:

National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
HIV Infections Hepatitis B Hepatitis C	Drug: Adefovir dipivoxil Drug: Peginterferon-alfa-2A Drug: Ribavirin Procedure: Liver Biopsy	Phase 2

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	Double
Primary Purpose:	Treatment
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 the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis B Hepatitis C

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00051077

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Dickens Theodore, M.D., Ph.D.	University of North Carolina, Chapel Hill
Study Chair:	Kenneth E Sherman, M.D., Ph.D	University of Cincinnati

More Information

Publications:

Benhamou Y, Bochet M, Thibault V, Calvez V, Fievet MH, Vig P, Gibbs CS, Brosgart C, Fry J, Namini H, Katlama C, Poynard T. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet. 2001 Sep 1;358(9283):718-23.

Soriano V, García-Samaniego J, Bravo R, González J, Castro A, Castilla J, Martínez-Odriozola P, Colmenero M, Carballo E, Suárez D, Rodríguez-Piñero FJ, Moreno A, del Romero J, Pedreira J, González-Lahoz J. Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group. Clin Infect Dis. 1996 Sep;23(3):585-91.

Xiong X, Flores C, Yang H, Toole JJ, Gibbs CS. Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro. Hepatology. 1998 Dec;28(6):1669-73.

McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998 Nov 19;339(21):1485-92.


ClinicalTrials.gov Identifier:	NCT00051077 History of Changes
Other Study ID Numbers:	A5149 10953 ( Registry Identifier: DAIDS ES Registry Number ) ACTG A5149
First Posted:	January 6, 2003 Key Record Dates
Last Update Posted:	May 18, 2012
Last Verified:	May 2012

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:


Hepatitis Hepatitis A Hepatitis C HIV Infections Hepatitis B Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Lentivirus Infections Retroviridae Infections	Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Hepadnaviridae Infections DNA Virus Infections Interferons Ribavirin Interferon-alpha Peginterferon alfa-2a Adefovir Adefovir dipivoxil Antineoplastic Agents Antiviral Agents Anti-Infective Agents

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