title: Phase I/II, open-label trial of safety and immunogenicity of meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine in human immunodeficiency virus-infected adolescents.
abstract: BACKGROUND
  Quadrivalent meningococcal polysaccharide conjugate vaccine (MCV4) is routinely recommended for healthy youth in the United States, but there are no data about its use in HIV-infected people.
  
  
  METHODS
  P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network. All youth (11-24 years old) received 1 dose of open-label MCV4 at entry. Standardized questionnaires were used to evaluate safety. Baseline protective immunity was defined as rabbit serum bactericidal antibody (rSBA) titer > or = 1:128. Immunogenic response was defined as a > or = 4-fold rise in rSBA against each meningococcal serogroup. Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C.
  
  
  RESULTS
  Among 319 subjects who received MCV4, 10 (3.1%) reported immediate adverse events which were local and mild, and 7 (2.2%) experienced Grade > or = 3 adverse events, unrelated to vaccine. The 305 subjects with serologic data had a median age of 17 years and were 59% male, 50% Black, and 38% Latino. Subjects were stratified by entry CD4%: 12%, CD4 <15%; 40%, 15% to 24%; and 48%, > or = 25%. Baseline protective immunity varied by serogroup: A, 41%; C, 11%; W-135, 15%; Y, 35% The immunogenic response rates to serogroups A, C, W-135, and Y were 68%, 52%, 73%, and 63%, respectively. In multivariable logistic regression models, lower entry CD4%, higher entry viral load, and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C.
  
  
  CONCLUSIONS
  Many HIV-infected youth naturally acquire meningococcal immunity. MCV4 is safe and immunogenic in HIV-infected youth, but response rates are lower than in healthy youth, particularly for those with more advanced HIV clinical, immunologic, and virologic status.
authors.affiliation: Pediatric, Adolescent, and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892-7510, USA. siberryg@mail.nih.gov
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Jorge
authors.initials: J
authors.lastname: Lujan-Zilbermann
authors.forename: Meredith G
authors.initials: MG
authors.lastname: Warshaw
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
authors.forename: Michael D
authors.initials: MD
authors.lastname: Decker
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Heckman
authors.forename: Emily F
authors.initials: EF
authors.lastname: Demske
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Read
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Philippe
authors.forename: William
authors.initials: W
authors.lastname: Kabat
authors.forename: Sharon
authors.initials: S
authors.lastname: Nachman
mesh_terms: D000293:Adolescent; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002648:Child; D004168:Diphtheria Toxoid / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000009:adverse effects* / Q000276:immunology*; D050296:Microbial Viability / Q000276:immunology; D038381:Neisseria meningitidis, Serogroup A / Q000276:immunology; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology; D038582:Neisseria meningitidis, Serogroup W-135 / Q000276:immunology; D038581:Neisseria meningitidis, Serogroup Y / Q000276:immunology; D011795:Surveys and Questionnaires; D014481:United States; D018074:Vaccines, Conjugate; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate