Tenofovir in HIV/HBV Coinfection

Study Overview
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Brief Summary
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The purpose of the study is to compare the effectiveness of 3 different treatment regimens in reducing or clearing the Hepatitis B Virus in patients infected with HIV and Hepatitis B (co-infection)

Detailed Description
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A randomised multi-centre trial of tenofovir vs lamivudine vs tenofovir/lamivudine in antiretroviral naïve subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A). Plus, a 12 week viral kinetic sub-study comparing a sub-group of the patients on Clinical Trial A with a group of therapy naïve HBV mono-infected subjects (Substudy A1)

Official Title
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Virological and Clinical Anti-HBV Efficacy of Tenofovir in Antiretroviral naïve Patients With HIV/HBV Co-infection

Conditions
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HIV Infection, Hepatitis B Coinfection

Intervention / Treatment
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* Drug: Tenofovir
* Drug: Zidovudine (AZT), lamivudine (LAM), efavirenz (EFV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Documented HIV infection (positive serology for HIV-1 and detectable HIV-1 RNA) Age 18 - 70 years HBV DNA > 105 copies/ml HBsAg positive >6 months or HBsAg positive and anti HB core IgM negative Creatinine <= 2.0mg/dl (<= 0.2 mmol/L) Platelet count >= 50,000/mm HIV-1 antiretroviral therapy naïve 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) Active opportunistic infection Other causes of chronic liver disease identified (autoimmune hepatitis, hemochromatosis, 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

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1:<br>Zidovudine (AZT), lamivudine (LAM), efavirenz (EFV) | Drug: Zidovudine (AZT), lamivudine (LAM), efavirenz (EFV)<br> <br> |
| Experimental: Arm 2<br>Zidovudine (AZT), tenofovir (TDF), efavirenz (EFV) | Drug: Tenofovir<br> <br> |
| Experimental: Amr 3<br>Lamivudine (LAM), tenofovir (TDF), efavirenz (EFV) | Drug: Tenofovir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare HBV DNA suppression to levels below the limit of detection (<400 copies/ml) by week 48 in each group |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -HBV resistance at 48 weeks; -undetectable HBV DNA at weeks 12 & 24; -HBeAg and HBsAg seroconversion at weeks 24 & 48; -ALT chnages and rate of hepatic cytolysis; -HIV-1 RNA supression and CD4/CD8 changes over 48 weeks; |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, HIV, Treatment Naive