title: Efficacy and immunogenicity of influenza vaccine in HIV-infected children:  a randomized, double-blind, placebo controlled trial.
abstract: BACKGROUND
  HIV-infected children are at heightened risk for severe influenza illness; however, there is no study on the efficacy or effectiveness of influenza vaccine in these children. We evaluated the safety, immunogenicity, and efficacy of nonadjuvanted, trivalent inactivated influenza vaccine (TIV) against confirmed seasonal influenza virus illness in HIV-infected children.
  
  
  METHODS
  A double-blind, placebo-controlled trial was undertaken in Johannesburg in 2009. Four hundred and ten children were randomized to two doses of TIV or placebo 1 month apart. Nasopharyngeal aspirates obtained at respiratory illness visits were tested by influenza-specific reverse transcriptase-PCR (RT-PCR). Vaccine immunogenicity was evaluated by hemagglutinin inhibition (HAI) assay. Influenza isolates were sequenced and evaluated in maximum likelihood phylogenetic analysis.
  
  
  RESULTS
  Overall, the median age of participants was 23.8 months and their median CD4% was 33.5. Ninety-two percent of enrolees were on antiretroviral therapy. Among children receiving both doses of vaccine/placebo, confirmed seasonal influenza illness occurred in 13 (all H3N2) of 205 TIV recipients and 17 (15 H3N2 and two influenza B) of 200 placebo recipients with vaccine efficacy of 17.7% (95% confidence interval <0-62.4%). The proportion of TIV recipients who seroconverted after second dose against vaccine strains of H1N1, H3N2, and influenza B were 47.5, 50.0, and 40.0%, compared to 4.7, 11.6, and 0%, respectively among placebo recipients. There were no TIV-related serious adverse events. Sequence analysis of wild-type H3N2 strains indicated drift from the H3N2 vaccine strain.
  
  
  CONCLUSIONS
  Poor immunogenicity of TIV, coupled with drift of circulating H3N2 wild-type compared to vaccine strain, may explain the lack of efficacy of TIV in young HIV-infected children. Alternate TIV vaccine schedules or formulations warrant evaluation for efficacy in HIV-infected children.
authors.affiliation: National Institute of Communicable Diseases, Centre for Respiratory and Meningitis Diseases, Sandringham, South Africa. shabirm@nicd.ac.za
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dittmer
authors.forename: Locadiah
authors.initials: L
authors.lastname: Kuwanda
authors.forename: Marietjie
authors.initials: M
authors.lastname: Venter
authors.forename: Haseena
authors.initials: H
authors.lastname: Cassim
authors.forename: Erica
authors.initials: E
authors.lastname: Lazarus
authors.forename: Teena
authors.initials: T
authors.lastname: Thomas
authors.forename: Afaaf
authors.initials: A
authors.lastname: Liberty
authors.forename: Florette
authors.initials: F
authors.lastname: Treurnich
authors.forename: Clare L
authors.initials: CL
authors.lastname: Cutland
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.forename: Avy
authors.initials: A
authors.lastname: Violari
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006679:HIV Seropositivity / Q000453:epidemiology / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006760:Hospitalization; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000302:isolation & purification; D009980:Influenza A virus / Q000276:immunology / Q000302:isolation & purification; D009981:Influenza B virus / Q000276:immunology / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008297:Male; D010802:Phylogeny; D011014:Pneumonia / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines