title: Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial.
abstract: BACKGROUND
  Revaccination with double-dose hepatitis B vaccine has been recommended in HIV-infected patients who do not respond to standard vaccination, but has not yet been assessed. We aimed to compare the safety and immunogenicity of a reinforced hepatitis B revaccination protocol with the standard revaccination schedule in HIV-infected patients not responding to primary vaccination.
  
  
  METHODS
  We did this multicentre, open-label, randomised controlled trial, at 53 centres in France. HIV-infected adults (aged ≥18 years), with CD4 counts of 200 cells per μL or more and no response to a previous hepatitis B vaccination or a 20 μg booster dose, were randomly assigned (1:1), according to a computer-generated randomisation list with permuted blocks (block sizes of two to six), to receive either standard-dose (20 μg) or double-dose (40 μg) recombinant hepatitis B vaccine at weeks 0, 4, and 24. Randomisation was stratified by baseline CD4 count (200-349 vs ≥350 cells per μL). Patients and treating physicians were not masked to treatment allocation, but the randomisation list was concealed from the investigators who assigned participants to the vaccination groups. The primary endpoint was the proportion of responders, defined as patients with hepatitis B surface antibody (anti-HBs) titres of 10 mIU/mL or more, at week 28. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00670839.
  
  
  RESULTS
  Between May 19, 2008, and May 8, 2011, 178 participants were randomly assigned to the standard-dose group (n=90) or the double-dose group (n=88), of whom 176 (98%) participants were included in the primary efficacy analysis. At week 28, we recorded a response in 60 patients (67%, 95% CI 57-77) in the standard-dose group versus 64 patients (74%, 63-82) in the double-dose group (p=0·334). Except for more frequent local reactions in the double-dose group than the standard-dose group (13 [15%] vs four [4%] patients; p=0·020), there was no difference in safety between groups.
  
  
  CONCLUSIONS
  In adults with HIV-1 who have not responded to previous hepatitis B vaccination, double-dose revaccination did not achieve a higher response rate than did revaccination with standard single-dose regimen. However, the safety profile was similar between treatment groups. Our results should be assessed in future studies before double-dose vaccine can be considered for the standard of care of vaccine non-responders.
  
  
  BACKGROUND
  French National Institute for Medical Research-French National Agency for Research on AIDS and Viral Hepatitis.
authors.affiliation: Le Trait d'Union, Center for HIV Care, Hôpitaux Universitaires Strasbourg, France. Electronic address: david.rey@chru-strasbourg.fr.
authors.forename: David
authors.initials: D
authors.lastname: Rey
authors.affiliation: Département d'Infectiologie, CHU Dijon, and UMR 1347, Université de Bourgogne, Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.affiliation: Laboratoire de Virologie, Hôpitaux Universitaires Strasbourg, France.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Wendling
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.affiliation: Laboratoire de Pathogenèse des virus de l'hépatite B, Institut Pasteur, Paris.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Michel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Cécilie
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Haour
authors.affiliation: Service d'hépatologie, Hôpital Cochin, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sogni
authors.affiliation: Agence Nationale De Recherche Sur Le Sida Et Les Hépatites (ANRS), Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rohel
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Gustave Dron, Tourcoing, France.
authors.forename: Faiza
authors.initials: F
authors.lastname: Ajana
authors.affiliation: Service des Maladies Infectieuses et Tropicales, CHU Nantes, Nantes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Billaud
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, and Inserm CIC 1417, and Assistance Publique Hôpitaux de Paris, Hôpital Cochin, CIC Cochin Pasteur, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; Département de santé publique, Groupe Hospitalier Est Parisien, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005602:France; D015658:HIV Infections / Q000276:immunology*; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic