title: Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults.
abstract: BACKGROUND
  The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy.
  
  
  METHODS
  A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™) was used. Serum hemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess immunogenicity.
  
  
  RESULTS
  297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL) and HIV RNA (76% of patients with viral load <50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥ 40 =  31-58%). Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related.
  
  
  CONCLUSIONS
  Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00764998.
authors.affiliation: University of Ottawa Division of Infectious Diseases, Ottawa, Canada. ccooper@ottawahospital.on.ca
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Anona
authors.initials: A
authors.lastname: Thorne
authors.forename: Marina
authors.initials: M
authors.lastname: Klein
authors.forename: Brian
authors.initials: B
authors.lastname: Conway
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
authors.forename: David
authors.initials: D
authors.lastname: Haase
authors.forename: Stephen
authors.initials: S
authors.lastname: Shafran
authors.forename: Wendy
authors.initials: W
authors.lastname: Zubyk
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
authors.forename: Scott
authors.initials: S
authors.lastname: Halperin
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
mesh_terms: D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D007252:Influenza Vaccines