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

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:

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

Drug Information available for: Zidovudine Emtricitabine Tenofovir Efavirenz Tenofovir Disoproxil Fumarate

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 (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator:	Kiat Ruxrungtham, MD PhD	HIVNAT Bangkok
Principal Investigator:	Jan Prins, MD PhD	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More Information


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:


Infection Communicable Diseases Hepatitis Hepatitis A HIV Infections Hepatitis B Coinfection Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Lentivirus Infections	Retroviridae Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Hepadnaviridae Infections DNA Virus Infections Parasitic Diseases Tenofovir Zidovudine Efavirenz Emtricitabine Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on September 29, 2016