Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection
- Conditions
- HIV InfectionsHepatitis B
- Registration Number
- NCT00127959
- Lead Sponsor
- International Antiviral Therapy Evaluation Center
- Brief Summary
This is a randomized multicentre trial of emtricitabine (FTC) versus tenofovir (TDF)/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).
Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)
- Detailed Description
This is a randomized multicentre trial of FTC vs TDF/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).
Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)
Primary Objectives:
* To compare the proportion of subjects with HBV DNA levels below the limit of detection (\<400 copies/ml) by week 48 in each treatment group
Secondary Objectives:
* To evaluate the emergence of HBV resistance at 48 weeks
* To compare the proportion of patients with undetectable HBV DNA at weeks 12 and 24 in each treatment group
* To compare the proportion of patients who achieve HBeAg and HBsAg seroconversion at weeks 12, 24 and 48 during the study
* To compare changes in ALT from baseline and the rate of hepatic cytolysis (ALT\>5x ULN)
* To compare suppression of HIV-1 RNA and changes in CD4/CD8 counts over 48 weeks
* To compare the effect of therapy on histological changes in the liver and the presence of ccc-DNA
Enrollment:
* 24 patients in Clinical trial A (of whom 16 enter substudy A1).
Clinical Trial A:
* Patients with HIV/HBV co-infection who are naive to HIV/HBV therapy, have detectable HBV viraemia and are willing to start antiretroviral therapy.
Inclusion Criteria:
* Written informed consent
* Documented HIV infection
* Age 18 - 70 years
* HBV DNA \> 106 copies/ml
Randomization:
* Arm 1: Zidovudine (AZT), emtricitabine (FTC), efavirenz (EFV)
* Arm 2: Tenofovir (TDF), emtricitabine (FTC), efavirenz (EFV)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- Written informed consent
- Documented HIV infection
- Age 18 - 70 years
- HBV DNA > 10E6 copies/ml
- ALT < 10 x ULN (upper limit of normal)
- Creatinine <= 2.0mg/dl
- Platelet count >= 50,000/mm3
- HIV-1 therapy naive
- No prior exposure to anti-HBV agents
- Hepatitis C viral RNA (CV-RNA) positive or Anti-hepatitis A virus immunoglobulin M (HAV IgM) positive
- Acute hepatitis (serum ALT > 1000 U/L)
- Prior LAM, TDF, or adefovir dipivoxil (ADV) therapy
- Active opportunistic infection
- Pregnancy or lactation
- Other chronic liver disease
- Concurrent malignancy requiring cytotoxic chemotherapy
- Decompensated or Child's C cirrhosis
- Alfa-fetoprotein (AFP) > 3X ULN (unless negative computed tomography [CT] scan or magnetic resonance imaging [MRI] within 3 months of entry date)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy
- Secondary Outcome Measures
Name Time Method Proportion of patients with undetectable HBV DNA in serum Rate of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion Rate of emergence of lamivudine (LAM)-resistant HBV genotypes Suppression of plasma HIV-RNA (< 50 copies/ml) Changes in CD4+ /CD8+ cell counts Presence of covalently closed circle DNA (cccDNA) on liver biopsy
Trial Locations
- Locations (1)
Academic Medical Center
🇳🇱Amsterdam, NH, Netherlands