Efficacy of Tenofovir and Emtricitabine in ARV-Naive Patients With HIV/HBV co-Infection - Full Text View

Sponsors and Collaborators:	The HIV Netherlands Australia Thailand Research Collaboration Gilead Sciences Ministry of Health, Thailand
Information provided by:	The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:	NCT00476463

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 II

MedlinePlus related topics: AIDS Hepatitis Hepatitis B

Drug Information available for: Zidovudine Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naive Patients With HIV/HBV co-Infection

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 ]

Estimated Enrollment:	24
Study Start Date:	April 2005
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator AZT+FTC+EFV	Drug: Emtricitabine Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV
2: Active Comparator 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:

HBsAg positive and
HBc core IgM antibody negative and
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

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

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) This link exits the ClinicalTrials.gov site

Responsible Party:	HIV-NAT ( Prof. Kiat Ruxrungtham )
Study ID Numbers:	HIV-NAT 023
Study First Received:	May 20, 2007
Last Updated:	February 15, 2008
ClinicalTrials.gov Identifier:	NCT00476463
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

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
Liver Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
Hepatitis, Viral, Human
Immunologic Deficiency Syndromes
Hepatitis
Virus Diseases
Digestive System Diseases

Emtricitabine
HIV Infections
Sexually Transmitted Diseases
Hepatitis B
Tenofovir
DNA Virus Infections
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Communicable Diseases
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Therapeutic Uses

Lentivirus Infections
Infection
Antiviral Agents
Hepadnaviridae Infections
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009