Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection
Information source: International Antiviral Therapy Evaluation Center
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Hepatitis B
Intervention: tenofovir (Drug); emtricitabine (Drug); zidovudine (Drug); efavirenz (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: International Antiviral Therapy Evaluation Center Official(s) and/or principal investigator(s): Joep M.A. Lange, MD PhD, Study Chair, Affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Kiat Ruxrungtham, MD PhD, Principal Investigator, Affiliation: HIVNAT Bangkok Jan Prins, MD PhD, Principal Investigator, Affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Summary
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)
Clinical Details
Official title: Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naïve Patients With HIV/HBV co-Infection
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy
Secondary outcome: Proportion of patients with undetectable HBV DNA in serumRate 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
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
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
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)
Locations and Contacts
Academic Medical Center, Amsterdam, NH 1105AZ, Netherlands
Additional Information
Starting date: March 2004
Last updated: April 23, 2007
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