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Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection

This study has been completed.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by:
International Antiviral Therapy Evaluation Center
ClinicalTrials.gov Identifier:
NCT00127959
First received: August 8, 2005
Last updated: April 23, 2007
Last verified: April 2007
History of Changes
  Purpose

This is a randomized multicentre trial of emtricitabine (FTC) versus tenofovir (TDF)/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).

Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)


Condition Intervention Phase
HIV Infections
Hepatitis B
 Drug: tenofovir
Drug: emtricitabine
Drug: zidovudine
Drug: efavirenz
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naïve Patients With HIV/HBV co-Infection

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by International Antiviral Therapy Evaluation Center:

Primary Outcome Measures:
  • HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy

Secondary Outcome Measures:
  • Proportion of patients with undetectable HBV DNA in serum
  • Rate of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion
  • Rate of emergence of lamivudine (LAM)-resistant HBV genotypes
  • Suppression of plasma HIV-RNA (< 50 copies/ml)
  • Changes in CD4+ /CD8+ cell counts
  • Presence of covalently closed circle DNA (cccDNA) on liver biopsy

Estimated Enrollment: 24
Study Start Date: March 2004
Study Completion Date: August 2006
Detailed Description:

This is a randomized multicentre trial of FTC vs TDF/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).

Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)

Primary Objectives:

  • To compare the proportion of subjects with HBV DNA levels below the limit of detection (<400 copies/ml) by week 48 in each treatment group

Secondary Objectives:

  • To evaluate the emergence of HBV resistance at 48 weeks
  • To compare the proportion of patients with undetectable HBV DNA at weeks 12 and 24 in each treatment group
  • To compare the proportion of patients who achieve HBeAg and HBsAg seroconversion at weeks 12, 24 and 48 during the study
  • To compare changes in ALT from baseline and the rate of hepatic cytolysis (ALT>5x ULN)
  • To compare suppression of HIV-1 RNA and changes in CD4/CD8 counts over 48 weeks
  • To compare the effect of therapy on histological changes in the liver and the presence of ccc-DNA

Enrollment:

  • 24 patients in Clinical trial A (of whom 16 enter substudy A1).

Clinical Trial A:

  • Patients with HIV/HBV co-infection who are naive to HIV/HBV therapy, have detectable HBV viraemia and are willing to start antiretroviral therapy.

Inclusion Criteria:

  • Written informed consent
  • Documented HIV infection
  • Age 18 – 70 years
  • HBV DNA > 106 copies/ml

Randomization:

  • Arm 1: Zidovudine (AZT), emtricitabine (FTC), efavirenz (EFV)
  • Arm 2: Tenofovir (TDF), emtricitabine (FTC), efavirenz (EFV)
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Documented HIV infection
  • Age 18 – 70 years
  • HBV DNA > 10E6 copies/ml
  • ALT < 10 x ULN (upper limit of normal)
  • Creatinine <= 2.0mg/dl
  • Platelet count >= 50,000/mm3
  • HIV-1 therapy naive
  • No prior exposure to anti-HBV agents

Exclusion Criteria:

  • Hepatitis C viral RNA (CV-RNA) positive or Anti-hepatitis A virus immunoglobulin M (HAV IgM) positive
  • Acute hepatitis (serum ALT > 1000 U/L)
  • Prior LAM, TDF, or adefovir dipivoxil (ADV) therapy
  • Active opportunistic infection
  • Pregnancy or lactation
  • Other chronic liver disease
  • Concurrent malignancy requiring cytotoxic chemotherapy
  • Decompensated or Child’s C cirrhosis
  • Alfa-fetoprotein (AFP) > 3X ULN (unless negative computed tomography [CT] scan or magnetic resonance imaging [MRI] within 3 months of entry date)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00127959

Locations
Netherlands
Academic Medical Center
Amsterdam, NH, Netherlands, 1105AZ
Sponsors and Collaborators
International Antiviral Therapy Evaluation Center
Gilead Sciences
Investigators
Study Chair: Joep M.A. Lange, MD PhD Academic Medical Center, Amsterdam
Principal Investigator: Kiat Ruxrungtham, MD PhD HIVNAT Bangkok
Principal Investigator: Jan Prins, MD PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00127959     History of Changes
Other Study ID Numbers: IAT-0038-04
Study First Received: August 8, 2005
Last Updated: April 23, 2007
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by International Antiviral Therapy Evaluation Center:
HIV-1
HBV
treatment
tenofovir
 emtricitabine
Treatment Naive
HIV-1 infection
Hepatitis B virus infection

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis B
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Liver Diseases
 Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Hepadnaviridae Infections
DNA Virus Infections
Zidovudine
Tenofovir
Tenofovir disoproxil
Efavirenz
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013