Efficacy and Tolerance of Peg-interferon Alpha 2a Added to Tenofovir and Emtricitabine in AgHBe Positive HBV-HIV Co-infected Patients

Study Overview
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Brief Summary
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HBe seroconversion is an important goal for anti-HBV treatment, since it is associated with a non progressive liver infection and a better clinical outcome. However, the rate of HBe seroconversion is low in HIV-HBV co-infected patients, mostly treated by tenofovir and emtricitabine. This study will evaluate the efficacy and the safety of a one-year Peg-interferon alpha 2a additional treatment in patients already treated by tenofovir and emtricitabine without reaching HBe seroconversion.

Detailed Description
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Many HBV-HIV co-infected patients are currently treated with dual activity drugs such as tenofovir and emtricitabine, often in combination. However, despite the potent antiviral activity of these drugs, the rate of HBe seroconversion is quite low, and not always sustained over time. HBe seroconversion is an important goal for anti-HBV treatment, since it is associated with a non progressive liver infection and a better clinical outcome. On the other hand, treatments with antiviral and immuno-modulator activity such as Peg-interferon, are infrequently used in co-infected patients, despite promising data in the field of HBV mono-infection with increased rates and sustained HBe seroconversions. This pilot study will evaluate the efficacy and the safety of a one-year Peg-interferon alpha 2a additional treatment (180 micro-g once a week, by injection), in 55 patients already treated by tenofovir and emtricitabine for at least 6 months, and who did not reached HBe seroconversion

Official Title
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Pilot Study on Efficacy and Tolerance of Peg-interferon Alpha-2a (Pegasys) Added to Tenofovir DF and Emtricitabine (Truvada) in AGHBe Positive HBV-HIV Co-infected Patients. ANRS HB 01 EMVIPEG.

Conditions
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Hepatitis B, HIV Infections

Intervention / Treatment
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* Drug: TRUVADA (EMTRICITABINE + TENOFOVIR DF)
* Biological: PEGASYS 180μg (Interféron pégylé alpha -2a)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infection Karnofsky above 80 per cent Stable ARV since 4 months CD4 above 200 per mm3 ARN VIH below 10000 copies per ml hepatitis B chronic with : positive antigenaemia HBe and negative antiHBe, positive DNA HBV before or under tenofovir treatment, DNA HBV negative or below 10000 copies per ml at W-8. Previous treatment by tenofovir and lamivudine or emtricitabine more than 6 months Exclusion Criteria: HIV 2 infection Hepatitis C or D Opportunistic infection Alcool consummation more than 50g/d Cirrhosis Pregnancy or plan of pregnancy Breastfeeding Immunosuppressive or modulating of the immune response treatment Other Hepatitis B treatments than tenofovir, lamivudine or emtricitabine since 6 months Malabsorption Exclusive HIV therapy with Truvada Evolutive cancer under chemotherapy

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV antiretroviral therapy, TRUVADA , PEGASYS 180μg<br>Week-8 up Week0: HIV antiretroviral therapy Week 0 up Week 48: HIV antiretroviral therapy + TRUVADA + PEGASYS 180μg Week 48 up Week 72: HIV antiretroviral therapy + TRUVADA Week 72 up Week 144: HIV antiretroviral therapy | Drug: TRUVADA (EMTRICITABINE + TENOFOVIR DF)<br>* Truvada ® (200 mg tablet of 300 mg of emtricitabine + tenofovir DF) Dosage 1 tablet taken orally once a day<br>Biological: PEGASYS 180μg (Interféron pégylé alpha -2a)<br>* Pegasys ® injection 180μg Dosage: A subcutaneous injection per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with seroconversion HBe (loose of HBe antigen and acquisition of HBe antibody) and HBV DNA below 2.3 log10 copies per ml |  | at Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with negative HBe antigen. |  | at Week 72 and Week 144 | 
| proportion of patients with HBV DNA under 2.3 log 10 copies per ml. |  | at Week 72 and Week 144 | 
| proportion of seroconversion HBs. |  | at Week 72 and Week 144 | 
| proportion of patients with no more HBs antigen. |  | at Week 72 and Week 144 | 
| proportion of patients with HBV DNA below 2.3 log 10 copies per ml in relation with 3TC resistance or not before tenofovir treatment; increased of ALT before tenofovir treatment;duration of tenofovir treatment before study. |  | before tenofovir treatment, duration of tenofovir treatment before study | 
| Biological evolution and histological of hepatic activity and fibrosis. |  | at day 0 and Week 72 | 
| Biochemical response (ALT at normal value). |  | at Week 72 and Week 144 | 
| proportion of patients with :seroconversion HBe and HBV DNA below 2.3 log 10 copies per ml |  | at Week 48 | 
| HBV and HIV resistance mutations to tenofovir DF and Emtricitabine. |  | at Week 72 | 
| Immunological and virological evolution of HIV infection. |  | between Day 0 and Week 144 | 
| Safety |  | between Day 0 and Week 144 | 
| Quality of life |  | Day 0, Week 12, Week 24, Week 48, Week 72 | 
| Treatment adherence |  | Day 0 to Week 144 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peg interferon, HIV and Hepatitis B coinfection, tenofovir, emtricitabine, Hepatitis B e Antigens, Treatment Experienced