Efficacy of Tenofovir and Emtricitabine in ARV-naive Patients With HIV/HBV Co-infection

This study has been completed.
Sponsor:
Collaborators:
Gilead Sciences
Ministry of Health, Thailand
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT00476463
First received: May 20, 2007
Last updated: June 4, 2010
Last verified: June 2010
  Purpose

Combination therapy with anti-HBV activity may both increase HBV suppression rates and reduce emergence of resistant strains. Several new therapeutic agents are currently in development, however combination therapy trials in the HBV-infected population have only recently commenced. No such trials have been undertaken in the HIV/HBV co-infected population.


Condition Intervention Phase
Hepatitis B Virus
HIV Infections
Drug: Emtricitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naive Patients With HIV/HBV Co-infection

Resource links provided by NLM:


Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:
  • HBV DNA suppression to levels below the limit of detection (<400 copies/ml) [ Time Frame: week 48 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • HBV suppression as measured by comparison of AUC measurements at 12 and 24 weeks [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of patients with undetectable HBV DNA in serum at 12 and 24 weeks [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: Yes ]
  • Rate of HBeAg and HBsAg seroconversion at 12, 24 and 48 weeks. [ Time Frame: 12, 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • Rate of emergence of LAM-resistant HBV genotypes at 48 weeks. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Rate of hepatic cytolysis (ALT level > 5x ULN). [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in ALT levels and time to ALT normalization. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Suppression of plasma HIV-RNA (< 50 copies/ml) through 48 weeks. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Changes in CD4+ /CD8+ cell counts through 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Assessment of effect of therapy on histological changes in the liver and effect on ccc-HBV-DNA [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: April 2005
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
AZT+FTC+EFV
Drug: Emtricitabine
Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV
Active Comparator: 2
TDF+FTC+EFV
Drug: Emtricitabine
Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV

Detailed Description:

The primary study objective is to compare HBV DNA suppression to levels below the limit of detection (<400 copies/ml) by week 48 in each treatment group. Virological and clinical anti-HBV efficacy of tenofovir and emtricitabine in antiretroviral naive patients with HIV/HBV co-infection.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Documented HIV infection (positive serology for HIV-1 and detectable HIV-1 RNA)
  • Age 18 - 70 years
  • HBV DNA > 106 copies/ml
  • HBsAg positive for > 6 months

In case documented duration of HBsAg seropositive is less than 6 months (this situation is most likely to occur in patients newly presenting to the HIV-outpatient clinic) the patient is eligible if the patient is:

  1. HBsAg positive and
  2. HBc core IgM antibody negative and
  3. the liver biopsy gives evidence for a chronic active hepatitis. Thus making it likely that this patient has acquired the HBV infection more than 6 months ago.

    • ALT < 10 x ULN
    • Creatinine <= 2.0mg/dl
    • Platelet count >= 50,000/mm3
    • HIV-1 therapy naive
    • No prior exposure to anti-HBV agents (LAM, adefovir, TDF) although prior IFN treatment allowed

Exclusion Criteria:

  • HCV-RNA positive or Anti-HAV IgM positive
  • Acute hepatitis (serum ALT > 1000 U/L)
  • Prior LAM, TDF, or ADV therapy
  • Active opportunistic infection
  • Other causes of chronic liver disease identified ( autoimmune hepatitis, haemochromatosis, Wilsons disease, alfa-1-antitrypsin deficiency)
  • Concurrent malignancy requiring cytotoxic chemotherapy
  • Decompensated or Child's C cirrhosis
  • Alfa-fetoprotein (AFP) > 3X ULN (unless negative CT scan or MRI within 3 months of entry date)
  • Pregnancy or lactation
  • Any other condition which in the opinion of the investigator might interfere with compliance or outcome of the study
  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: NCT00476463

Locations
Thailand
HIV-NAT Thai Red Cross AIDS Research Center
Bangkok, Thailand, 10330
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
Gilead Sciences
Ministry of Health, Thailand
Investigators
Principal Investigator: Kiat Ruxrungtham, MD HIV-NAT Thai Red Cross AIDS Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Kiat Ruxrungtham, HIV-NAT
ClinicalTrials.gov Identifier: NCT00476463     History of Changes
Other Study ID Numbers: HIV-NAT 023
Study First Received: May 20, 2007
Last Updated: June 4, 2010
Health Authority: Thailand: Food and Drug Administration

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
TDF+FTC
FTC
HIV/HBV
TDF compared to TDF+FTC in HIV/HBV
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis B
Coinfection
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
Infection
Parasitic Diseases
Tenofovir
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014