trial comparing two strategies of vaccination against hepatitis b in hiv-infected patients non responding to primary immunization (b-boost)

Conditions: Hepatitis B; HIV Infection

Summary: 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

Eligibility criteria:
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

Keywords: hepatitis b vaccination genhevac-b pasteur hiv infection