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

Study Overview
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Brief Summary
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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
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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)

Official Title
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Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naïve Patients With HIV/HBV co-Infection

Conditions
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HIV Infections, Hepatitis B

Intervention / Treatment
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* Drug: tenofovir
* Drug: emtricitabine
* Drug: zidovudine
* Drug: efavirenz


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tenofovir|nan|
|Drug: emtricitabine|nan|
|Drug: zidovudine|nan|
|Drug: efavirenz|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, HBV, treatment, tenofovir, emtricitabine, Treatment Naive, HIV-1 infection, Hepatitis B virus infection