title: Trivalent inactivated influenza vaccine in African adults infected with human immunodeficient virus: double blind, randomized clinical trial of efficacy, immunogenicity, and safety.
abstract: BACKGROUND
  Data on the efficacy of trivalent, inactivated influenza vaccine (TIV) in HIV-infected adults, particularly in Africa, are limited. This study evaluated the safety, immunogenicity, and efficacy of TIV in HIV-infected adults.
  
  
  METHODS
  In Johannesburg, South Africa, we undertook a randomized, double-blind, placebo-controlled trial involving 506 HIV-infected adults. Subjects included 157 individuals who were antiretroviral treatment (ART) naive and 349 on stable-ART. Participants were randomly assigned to receive TIV or normal saline intramuscularly. Oropharyngeal swabs were obtained at illness visits during the influenza season and tested by shell vial culture and RT PCR assay for influenza virus. Immune response was evaluated by hemagglutinin antibody inhibition assay (HAI) in a nested cohort. The primary study outcome involved vaccine efficacy against influenza confirmed illness. This trial is registered with ClinicalTrials.gov, number NCT00757900.
  
  
  RESULTS
  The efficacy of TIV against confirmed influenza illness was 75.5% (95% CI: 9.2%-95.6%); with a risk difference of 0.18 per 100 person-weeks in TIV recipients. Among TIV recipients, seroconversion, measured by HAI titers, was evident in 52.6% for H1N1, 60.8% for H3N2, and 53.6% for influenza B virus. This compared with 2.2%, 2.2%, and 4.4% of placebo recipients (P < .0001). The frequency of local and systemic adverse events post-immunization was similar between study groups.
  
  
  CONCLUSIONS
  TIV immunization is safe and efficacious in African HIV-infected adults without underlying co-morbidities. Further evaluation of effectiveness is warranted in severely immunocompromized HIV-infected adults and those with co-morbidities such as tuberculosis.
authors.affiliation: Department of Science and Technology/ National Research Foundation, Vaccine Preventable Diseases, University of Witwatersrand, South Africa. madhis@rmpru.co.za
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Mhairi
authors.initials: M
authors.lastname: Maskew
authors.forename: Anthonet
authors.initials: A
authors.lastname: Koen
authors.forename: Locadiah
authors.initials: L
authors.lastname: Kuwanda
authors.forename: Terry G
authors.initials: TG
authors.lastname: Besselaar
authors.forename: Dhamari
authors.initials: D
authors.lastname: Naidoo
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cohen
authors.forename: Martine
authors.initials: M
authors.lastname: Valette
authors.forename: Clare L
authors.initials: CL
authors.lastname: Cutland
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D009981:Influenza B virus / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009960:Oropharynx / Q000821:virology; D010919:Placebos / Q000008:administration & dosage; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013019:South Africa; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014776:Virus Cultivation; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D010919:Placebos; D012367:RNA, Viral; D015164:Vaccines, Inactivated