title: Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN.
abstract: OBJECTIVE
  The antiviral efficacy of nucleos(t)ide analogues whose main limitation is relapse after discontinuation requires long-term therapy. To overcome the risk of relapse and virological breakthrough during long-term therapy, we performed a phase I/II, open, prospective, multicentre trial using a HBV envelope-expressing DNA vaccine.
  
  
  METHODS
  70 patients treated effectively with nucleos(t)ide analogues for a median of 3 years (HBV DNA <12 IU/mL for at least 12 months) were randomised into two groups: one received five intramuscular injections of vaccine (weeks 0, 8, 16, 40 and 44) and one did not receive the vaccine. Analogues were stopped after an additional 48 weeks of treatment in patients who maintained HBV DNA <12 IU/mL with no clinical progression and monthly HBV DNA for 6 months. The primary endpoint was defined as viral reactivation at week 72 (HBV DNA >120 IU/mL) or impossibility of stopping treatment at week 48.
  
  
  RESULTS
  Reactivation occurred in 97% of each group after a median 28 days without liver failure but with an HBV DNA <2000 IU/mL in 33%; 99% of adverse reactions were mild to moderate. Immune responses were evaluated by enzyme-linked immunosorbent spot and proliferation assays: there was no difference in the percentage of patients with interferon-γ secreting cells and a specific T-cell proliferation to HBcAg but not to HBsAg after reactivation in each group.
  
  
  CONCLUSIONS
  Although it is fairly well tolerated, the HBV DNA vaccine does not decrease the risk of relapse in HBV-treated patients or the rate of virological breakthrough, and does not restore the anti-HBV immune response despite effective viral suppression by analogues.
  
  
  BACKGROUND
  NCT00536627.
authors.affiliation: Institut Cochin, CNRS (UMR 8104) and INSERM U-1016, Université Paris Descartes, et Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, Cochin Hospital, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Kahi
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Chazallon
authors.affiliation: Laboratoire de pathogénèse des virus de l'hépatite B and INSERM U845, Institut Pasteur, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bourgine
authors.affiliation: Gastroenterology and Hepatology Unit, Pitié-Salpétrière Hospital, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Varaut
authors.affiliation: Gastroenterology and Hepatology Unit, Kremlin-Bicêtre Hospital, le Kremlin-Bicêtre, France.
authors.forename: C
authors.initials: C
authors.lastname: Buffet
authors.affiliation: Laboratoire de pathogénèse des virus de l'hépatite B and INSERM U845, Institut Pasteur, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Godon
authors.affiliation: Virology Unit, Cochin Hospital, Paris, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Meritet
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Saïdi
authors.affiliation: Laboratoire de pathogénèse des virus de l'hépatite B and INSERM U845, Institut Pasteur, Paris, France.
authors.forename: M L
authors.initials: ML
authors.lastname: Michel
authors.affiliation: Unité de Régulation des Infections Rétrovirales, Institut Pasteur.
authors.forename: D
authors.initials: D
authors.lastname: Scott-Algara
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Aboulker
authors.affiliation: Institut Cochin, CNRS (UMR 8104) and INSERM U-1016, Université Paris Descartes, et Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, Cochin Hospital, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Pol
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D017325:Hepatitis B Vaccines; D019694:Hepatitis B, Chronic / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D017211:Treatment Failure; D019444:Vaccines, DNA
chemical_list: D000998:Antiviral Agents; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA