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

HIV Infections Clinical Trial

Official title:

Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naive Patients With HIV/HBV Co-infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00476463
• Other study ID #: HIV-NAT 023
• Status: Completed
• Phase: Phase 2
• First received: May 20, 2007
• Last updated: February 18, 2016
• Start date: April 2005
• Est. completion date: December 2008

Study information

• Verified date: February 2016
• Source: The HIV Netherlands Australia Thailand Research Collaboration
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis B Virus
• HIV Infections
• Infection

Intervention

Drug:
• Emtricitabine
Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV

Locations

Country	Name	City	State
Thailand	HIV-NAT Thai Red Cross AIDS Research Center	Bangkok

Sponsors (3)

Lead Sponsor	Collaborator
The HIV Netherlands Australia Thailand Research Collaboration	Gilead Sciences, Ministry of Health, Thailand

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBV DNA suppression to levels below the limit of detection (<400 copies/ml)		week 48	Yes
Secondary	HBV suppression as measured by comparison of AUC measurements at 12 and 24 weeks		12 and 24 weeks	Yes
Secondary	Proportion of patients with undetectable HBV DNA in serum at 12 and 24 weeks		12 and 24 weeks	Yes
Secondary	Rate of HBeAg and HBsAg seroconversion at 12, 24 and 48 weeks.		12, 24 and 48 weeks	Yes
Secondary	Rate of emergence of LAM-resistant HBV genotypes at 48 weeks.		48 weeks	Yes
Secondary	Rate of hepatic cytolysis (ALT level > 5x ULN).		48 weeks	Yes
Secondary	Change from baseline in ALT levels and time to ALT normalization.		48 weeks	Yes
Secondary	Suppression of plasma HIV-RNA (< 50 copies/ml) through 48 weeks.		48 weeks	Yes
Secondary	Changes in CD4+ /CD8+ cell counts through 48 weeks		48 weeks	Yes
Secondary	Toxicity		48 weeks	Yes
Secondary	Assessment of effect of therapy on histological changes in the liver and effect on ccc-HBV-DNA		48 weeks	No

External Links

•   The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)