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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Withdrawn

CT.gov ID

NCT00051077

Collaborator

(none)

Enrollment

Study Details

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

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

No locations specified.

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