Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection

International Antiviral Therapy Evaluation Center24 enrolled

Overview

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)

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infections Hepatitis B

Interventions

tenofovirDRUG

emtricitabineDRUG

zidovudineDRUG

efavirenzDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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)

Locations (1)

Academic Medical Center

Amsterdam, North Holland, Netherlands

Outcomes

Primary Outcomes

HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy

Secondary Outcomes

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

Data from ClinicalTrials.gov

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