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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hepatitis B Virus, HIV Infections

Intervention / Treatment
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* Drug: Emtricitabine


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 > 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: HBsAg positive and HBc core IgM antibody negative and 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: 1<br>AZT+FTC+EFV | Drug: Emtricitabine<br>* Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV<br>|
| Active Comparator: 2<br>TDF+FTC+EFV | Drug: Emtricitabine<br>* Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TDF+FTC, FTC, HIV/HBV, TDF compared to TDF+FTC in HIV/HBV, Treatment Naive