title: Pneumococcal conjugate vaccination in persons with HIV: the effect of highly active antiretroviral therapy.
abstract: OBJECTIVE
  Vaccination responses may be affected by concomitant use of highly active antiretroviral therapy (HAART). We aimed to determine HAART's impact on seven-valent pneumococcal conjugate (7vPnC) vaccine immunization with or without a Toll-like receptor 9 (TLR9) agonist adjuvant.
  
  
  METHODS
  Observational cohort study.
  
  
  METHODS
  Adults with HIV were immunized with double doses of 7vPnC +/-1 mg CPG 7909, a TLR9 agonist and vaccine adjuvant, at 0 and 3 months, and 23-valent pneumococcal polysaccharide vaccine at 9 months. We measured IgG levels (ELISA) and opsonophagocytic activity (OPA) at months 0, 3, 4, 9, and 10. Persistent 7vPnC vaccine responders were defined as individuals with two-fold IgG increases to 1 microg/ml or more for at least five of the 7vPnC serotypes at 9 months.
  
  
  RESULTS
  We included 75 participants on HAART and 20 HAART-naive. Forty-one received CPG 7909 and 48 received placebo adjuvant. More persistent 7vPnC vaccine responders were found among HAART-treated than among HAART-naive (42.3 vs. 15.0%, P = 0.03). Mean loss of vaccine-specific IgG from month 4 to 9 was greater among HAART-naive than among HAART-treated (54.8 vs. 38.1%, P = 0.001). Functional activity (OPA) was higher among HAART-treated than among HAART-naive at 4, 9, and 10 months. In a logistic regression analysis (adjusted for baseline CD4 cell count, CPG 7909, smoking status, BMI, AIDS diagnosis, and age), HAART use was significantly associated with being persistent 7vPnC vaccine responder at month 9 [odds ratio = 4.65, 95% confidence interval (CI) 1.07-20.2].
  
  
  CONCLUSIONS
  HIV-infected adults on HAART achieved a more durable antibody response of higher functional activity following pneumococcal conjugate vaccination than HAART-naive individuals, independently of baseline CD4 cell count.
authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark. olesoega@rm.dk <olesoega@rm.dk>
authors.forename: Ole S
authors.initials: OS
authors.lastname: Søgaard
authors.forename: Henrik C
authors.initials: HC
authors.lastname: Schønheyder
authors.forename: Anne R
authors.initials: AR
authors.lastname: Bukh
authors.forename: Zitta B
authors.initials: ZB
authors.lastname: Harboe
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rasmussen
authors.forename: Lars
authors.initials: L
authors.lastname: Ostergaard
authors.forename: Nicolai
authors.initials: N
authors.lastname: Lohse
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000517:prevention & control*; D000328:Adult; D000917:Antibody Formation; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003718:Denmark; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D051217:Toll-Like Receptor 9 / Q000097:blood; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D022242:Pneumococcal Vaccines; C483020:ProMune; D012367:RNA, Viral; D051217:Toll-Like Receptor 9; D018074:Vaccines, Conjugate