Trial Comparing Two Strategies of Vaccination Against Hepatitis B in HIV-infected Patients Non Responding to Primary Immunization (B-BOOST)

Open-label, Randomized, and Multicenter Phase III Clinical Trial Comparing Immunogenicity of Double-dose (40 µg at S0, S4 and S24), Versus Standard Dose Vaccination (20 µg at S0, S4 and S24), Against Hepatitis B Virus in HIV-1-infected Patients Without Any Previous Immune Response After Primary Immunization Plus One Single Boost

HIV infected patients exposed to Hepatitis B virus are more susceptible to develop a chronic and severe liver disease, with a major risk of cirrhosis and liver cancer.

However, immune response to standard Hepatitis B vaccination is decreased in HIV-infected patients, compared to non HIV-infected individuals, and, in case of response, its durability has to be carefully followed up. This study compares the efficacy of two strategies of revaccination in HIV-infected patients who didn't respond to previous hepatitis B vaccination. Failure is defined by two conditions: non response to the primary immunization (2 to 4 single-dose injections received before the screening visit) and failure to a single 20 µg boost before being included in the study.

Comparison of 2 revaccination strategies in randomized HIV-infected patients with T CD4 cell count above 200/mm3

Intervention:

1. Arm A: GenHevac-B® 20μg IM at M0, M1, M6
2. Arm B: GenHevac-B® 40μg IM at M0, M1, M6

Inclusion Criteria:

• HIV-1 infection
• T CD4 cell count number above 200 /mm3
• History of 2 to 4 injections of Hepatitis B vaccine, at any time in the past
• No history of Hepatitis B vaccination with a double-dose schedule
• No response to Hepatitis B vaccination: serology Hepatitis B negative (AgHBs, AbHBs and AbHBc negative) the previous twelve months and at the screening visit
• AbHBs titers below 10 IU/ml four weeks after the boost of Genhevac-B® 20μg preceding the randomization
• unchanged ARV treatment for the last 2 months for patients who are receiving ARV at the screening visit
• Undetectable HIV RNA for the last 6 months and on-going ARV for any patients with T CD4 cell level below 350/mm3
• HIV-1 plasma load below 100 000 copies per ml for patients without ARV
• Negative pregnancy test at the screening visit, and immediately before the Genhevac-B® 20 µg boost injection preceding the randomization

Exclusion Criteria:

• Acute cytolysis in the last 3 months with transaminases equal or above 5 times the upper limit of normal for HIV-HCV coinfected patients, or transaminases equal or above 2 times the upper limit of normal for non coinfected patients
• Any vaccine received during the month preceding the inclusion
• History of hypersensitivity to any component of GenHevac-B
• acute opportunistic infection treated the month before the screening visit
• Severe and acute pyretic infection or unexplained fever the week before inclusion
• Hemopathy or solid-organ cancer
• Prothrombin factor equal or below 50% 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 at least 7 days) in the last 6 months before the screening visit
• Immunomodulating treatment (interferon, interleukine-2,…) in the last 6 months before the screening visit
• Splenectomy
• Decompensated cirrhosis (Child Pugh B or C)
• Renal failure (creatinine clearance below 50 ml/mn)
• Other severe 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