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

NCT ID: NCT00051077

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Brief Summary

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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).

Detailed Description

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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.

Conditions

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HIV Infections Hepatitis B Hepatitis C

Keywords

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HIV Infections Hepatitis B Hepatitis C Interferon Alfa-2a Adefovir dipivoxil Ribavirin Antiviral Agents Drug Resistance, Viral Treatment Experienced

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Adefovir dipivoxil

Intervention Type DRUG

Peginterferon-alfa-2A

Intervention Type DRUG

Ribavirin

Intervention Type DRUG

Liver Biopsy

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Principal Investigators

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Dickens Theodore, M.D., Ph.D.

Role: STUDY_CHAIR

University of North Carolina, Chapel Hill

Kenneth E Sherman, M.D., Ph.D

Role: STUDY_CHAIR

University of Cincinnati

Countries

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United States

References

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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. doi: 10.1016/s0140-6736(01)05840-8.

Reference Type BACKGROUND
PMID: 11551579 (View on PubMed)

Soriano V, Garcia-Samaniego J, Bravo R, Gonzalez J, Castro A, Castilla J, Martinez-Odriozola P, Colmenero M, Carballo E, Suarez D, Rodriguez-Pinero FJ, Moreno A, del Romero J, Pedreira J, Gonzalez-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. doi: 10.1093/clinids/23.3.585.

Reference Type BACKGROUND
PMID: 8879784 (View on PubMed)

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. doi: 10.1002/hep.510280629.

Reference Type BACKGROUND
PMID: 9828233 (View on PubMed)

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. doi: 10.1056/NEJM199811193392101.

Reference Type BACKGROUND
PMID: 9819446 (View on PubMed)

Other Identifiers

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10953

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5149

Identifier Type: -

Identifier Source: secondary_id

A5149

Identifier Type: -

Identifier Source: org_study_id