title: Impaired immunity to recall antigens and neoantigens in severely immunocompromised children and adolescents during the first year of effective highly active antiretroviral therapy.
abstract: BACKGROUND
  We studied whether severely immunocompromised, human immunodeficiency virus (HIV)-infected children who were beginning highly active antiretroviral therapy (HAART) or changing HAART regimens could spontaneously respond to a recall antigen (tetanus toxoid [TT] vaccine) or respond to a recall antigen and neoantigen (hepatitis A virus [HAV] vaccine) after 3 vaccinations.
  
  
  METHODS
  A total of 46 children who had CD4 cell percentages <15% and who demonstrated a >0.75-log reduction in plasma HIV RNA levels within 4 weeks of starting HAART were randomized to receive vaccinations with either TT or HAV vaccines during the first 6 months of HAART. Study subjects then received the alternate vaccine during the next 6 months of HAART.
  
  
  RESULTS
  Despite the early decline in viremia and the later increase in the percentage of CD4 T cells, spontaneous recovery of cell-mediated immunity (CMI) was not seen for TT. Serologic responses to TT required 3 vaccinations and were comparable in both groups. Serologic responses to HAV were infrequent and of low titer, although the group that received HAV vaccine after receiving TT vaccine performed somewhat better. CMI to HAV was virtually absent.
  
  
  CONCLUSIONS
  Severely immunocompromised children who are receiving HAART develop CMI and antibody to a recall antigen independent of the timing of vaccination, but they require a primary series of vaccinations. Antibodies to a neoantigen, HAV, developed when vaccination was delayed after initiation of HAART. CMI to a neoantigen was difficult to establish.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier: NCT00004735/PACTG P1006 .
authors.affiliation: New York University School of Medicine, New York, NY, USA. mona.rigaud@med.nyu.edu
authors.forename: Mona
authors.initials: M
authors.lastname: Rigaud
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.forename: Petronella
authors.initials: P
authors.lastname: Muresan
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.forename: Phillip
authors.initials: P
authors.lastname: Larussa
authors.forename: Terry
authors.initials: T
authors.lastname: Fenton
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Read
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Philippe
authors.forename: Elaine
authors.initials: E
authors.lastname: Fergusson
authors.forename: Bonnie
authors.initials: B
authors.lastname: Zimmer
authors.forename: Dorothy
authors.initials: D
authors.lastname: Smith
authors.forename: Joyce
authors.initials: J
authors.lastname: Kraimer