Trial Comparing Three Strategies of Vaccination Against the Virus of Hepatitis B in HIV Infected Patients

Study Overview
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Brief Summary
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In HIV infected patients, individuals exposed to the virus of Hepatitis B are more susceptible to develop a chronic and severe liver disease with a major risk of cirrhosis and liver cancer. However, the existing protocol of vaccination against Hepatitis B is less efficient in HIV-infected patients than in non HIV-infected-patients, and, in case of response, its longevity has to be followed up carefully. This study compares the efficacy of the standard protocol vaccination with GenHevac-B and 2 other protocols, a double-dose of GenHevac-B and a set of intradermal injections of Genhevac-B, in HIV-infected patients with lymphocytes T CD4 level above 200 permm3.

Detailed Description
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Comparison of 3 vaccination strategy against Hepatitis B in patients with HIV infection T CD4 above 200 per mm3 Intervention: Arm A: GenHevac-B 20 microgramme Intramuscular use at M0, M1, M6 Arm B: GenHevac-B 40 microgramme Intramuscular use at M0, M1, M2, M6 Arm C: GenHevac-B 4 microgramme Intradermal use at M0, M1, M2, M6

Official Title
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Open-label, Randomized, and Multicentric Phase III Clinical Trial Comparing Three Strategies of Vaccination Against the Virus of Hepatitis B in HIV-1-infected Patients With CD4-positive T-lymphocytes Counts Above 200 permm3 ANRS HB 03 VIHVAC-B

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: GenHevac B Pasteur
* Biological: GenHevac B Pasteur
* Biological: GenHevac B Pasteur


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age Eligible for Study: 18 years - NA, Genders Eligible for Study: Both Criteria Inclusion criteria: HIV infection T CD4 count cell level above 200 per mm3 Serology Hepatitis B negative (AgHBs, AbHBs and AbHBc negative) unchanged ARV for the last 3 months for patients who are receiving ARV at the screening visit Undetectable for the last 6 months with ARV for any patient with T CD4 level below 350 per mm3 Pregnancy test negative at the screening and inclusion visits Exclusion Criteria: Any injection of the vaccine against Hepatitis B in the medical history Acute cytolysis in the last 3 months with transaminases equal or above 5 times the upper normal range for HIV-HCV coinfected patients, or transaminases equal or above 2 times the upper normal for non coinfected patients Any vaccine received one month before the inclusion History of intolerance to any component of GenHevac-B Evolutive opportunistic infection treated the month before the screening visit Severe and acute pyretic infection or unexplained fever the week before inclusion Evolutive hemopathy or solid-organ cancer Prothrombin factor equal or below 50 percent and/or platelets equal or below 50 000 per mm3 Immunosuppressive treatment or general corticotherapy (equal or above 0,5 mg per kg per day during above 7 days) in the last 6 months before the screening visit Previous Immunomodulating treatment (interferon, interleukin-2,etc) or plan in the next 6 months Splenectomy Decompensated cirrhosis (Child Pugh B or C) Kidney deficient function (creatinine clearance below 50 ml per mn) Other immunocompromised condition not related to HIV infection (solid-organ transplantation, chemotherapy in the last 6 months) Any participation to another clinical trial plan until Week 28

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>GenHevac-B 20 microgramme Intramuscular use at M0, M1, M6 | Biological: GenHevac B Pasteur<br>* Intra-muscular injection 20 microgramme Intramuscular use at M0, M1, M6<br>* Other names: Sanofi Pasteur MSD;|
| Experimental: B<br>GenHevac-B 40 microgramme Intramuscular use at M0, M1, M2, M6 | Biological: GenHevac B Pasteur<br>* Intra-muscular injection 40 microgramme intramuscular use at M0, M1,M2, M6<br>* Other names: Sanofi Pasteur MSD;|
| Experimental: C<br>GenHevac-B 4 microgramme Intradermal use at M0, M1, M2, M6 | Biological: GenHevac B Pasteur<br>* GenHevac-B 4 microgramme Intradermal use at M0, M1, M2, M6<br>* Other names: Sanofi Pasteur MSD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-infected patients who seroconvert in the first two months after the last vaccination. Seroconversion is defined as antibodies AbHBs titers equal or above 10 mUI per ml. |  | two months after the last injection;week 28, month 18, month 30 and month 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| According to the vaccine administration (IM or ID) comparison of AbHBs titers,permanence of the humoral response,intensity of clinical and biological events and predicting factors related to seroconversion |  | two months after the last injection; week 28, month 18, month 30 and month 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B vaccination, GenHevac-B Pasteur, HIV Infections