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

Phase 2

Completed

• Conditions: Hepatitis B Virus; HIV Infections
• Interventions: Drug: Emtricitabine

• Registration Number: NCT00476463
• Lead Sponsor: The HIV Netherlands Australia Thailand Research Collaboration

Brief 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.

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.

Study Timeline

• Study Start: 2005-04
• Study First Submitted: 2007-05-20
• Study First Submitted QC: 2007-05-21
• Study First Posted: 2007-05-22
• Primary Completion: 2008-12
• Study Completion: 2008-12
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-18
• Last Update Posted: 2016-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Emtricitabine	TDF+FTC+EFV
1	Emtricitabine	AZT+FTC+EFV

Primary Outcome Measures

Name	Time	Method
HBV DNA suppression to levels below the limit of detection (<400 copies/ml)	week 48

Secondary Outcome Measures

Name	Time	Method
HBV suppression as measured by comparison of AUC measurements at 12 and 24 weeks	12 and 24 weeks
Proportion of patients with undetectable HBV DNA in serum at 12 and 24 weeks	12 and 24 weeks
Rate of HBeAg and HBsAg seroconversion at 12, 24 and 48 weeks.	12, 24 and 48 weeks
Rate of emergence of LAM-resistant HBV genotypes at 48 weeks.	48 weeks
Rate of hepatic cytolysis (ALT level > 5x ULN).	48 weeks
Change from baseline in ALT levels and time to ALT normalization.	48 weeks
Suppression of plasma HIV-RNA (< 50 copies/ml) through 48 weeks.	48 weeks
Changes in CD4+ /CD8+ cell counts through 48 weeks	48 weeks
Toxicity	48 weeks
Assessment of effect of therapy on histological changes in the liver and effect on ccc-HBV-DNA	48 weeks

Trial Locations

Locations (1)

HIV-NAT Thai Red Cross AIDS Research Center; 🇹🇭 Bangkok, Thailand