title: Strong serological responses and HIV RNA increase following AS03-adjuvanted pandemic immunization in HIV-infected patients.
abstract: BACKGROUND
  We aimed to determine the antibody responses and effect on viral load of the AS03-adjuvanted pandemic H1N1 vaccine in HIV-infected patients.
  
  
  METHODS
  A total of 121 HIV-infected patients and 138 healthy subjects were enrolled in a prospective, open-label study. Healthy subjects received one dose and HIV-infected patients two doses of the AS03-adjuvanted split influenza A/09/H1N1 vaccine (Pandemrix®; GlaxoSmithKline, Brentford, United Kingdom.) at an interval of 3-4 weeks. The study was extended in 2010/2011 for 66 patients. Geometric mean titres (GMTs), seroprotection rates (post-vaccination titre ≥ 1:40) and HIV-1 RNA levels were measured before and 4 weeks after immunization.
  
  
  RESULTS
  After two immunizations, the seroprotection rate (94.2 vs. 87%, respectively) and GMT (376 vs. 340, respectively) in HIV-infected patients were as high as in healthy subjects after one dose, regardless of CD4 cell count. Four weeks after immunization, HIV RNA was detected in plasma samples from 40 of 68 (58.0%) previously aviraemic patients [median 152 HIV-1 RNA copies/mL; interquartile range (IQR) 87-509 copies/mL]. Subsequent measures indicated that HIV RNA levels had again declined to <20 copies/mL in most patients (27 of 34; 79.4%). Following (nonadjuvanted) influenza immunization in 2010/2011, HIV RNA levels only slightly increased (median final level 28 copies/mL) in three of 66 (4.5%) previously aviraemic patients, including two of 25 (8%) patients in whom an increase had been elicited by AS03-adjuvanted vaccine the year before.
  
  
  CONCLUSIONS
  Most HIV-infected patients developed seroprotection after two doses of AS03-adjuvanted pandemic vaccine. A transient effect on HIV RNA levels was observed in previously aviraemic patients. A booster dose of the nonadjuvanted influenza vaccine containing the A/09/H1N1 strain the following year did not reproduce this finding, indicating a non-antigen-specific adjuvant effect.
authors.affiliation: Division of Infectious Diseases, HIV Unit, Department of Internal Medicine, University Hospitals of Geneva, Switzerland. alexandra.calmy@hcuge.ch
authors.forename: A
authors.initials: A
authors.lastname: Calmy
authors.forename: M
authors.initials: M
authors.lastname: Bel
authors.forename: A
authors.initials: A
authors.lastname: Nguyen
authors.forename: C
authors.initials: C
authors.lastname: Combescure
authors.forename: C
authors.initials: C
authors.lastname: Delhumeau
authors.forename: S
authors.initials: S
authors.lastname: Meier
authors.forename: S
authors.initials: S
authors.lastname: Yerly
authors.forename: L
authors.initials: L
authors.lastname: Kaiser
authors.forename: B
authors.initials: B
authors.lastname: Hirschel
authors.forename: C-A
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D012367:RNA, Viral; C556153:pandemrix; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol