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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Hepatitis B Virus
• Intervention / Treatment: Drug: Emtricitabine

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • HIV-NAT Thai Red Cross AIDS Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration
• Collaborators: Gilead Sciences; Ministry of Health, Thailand
• Investigators: Principal Investigator: Kiat Ruxrungtham, MD, HIV-NAT Thai Red Cross AIDS Research Center

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: May 20, 2007
• First Submitted That Met QC Criteria: May 21, 2007
• First Posted (Estimate): May 22, 2007

Study Record Updates

• Last Update Posted (Estimate): February 22, 2016
• Last Update Submitted That Met QC Criteria: February 18, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Treatment Naive; FTC; TDF+FTC; HIV/HBV; TDF compared to TDF+FTC in HIV/HBV
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Infections; Communicable Diseases; Hepatitis B; Coinfection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine
• Other Study ID Numbers: HIV-NAT 023