title: Antibody responses to hepatitis A virus vaccine in HIV-infected children with evidence of immunologic reconstitution while receiving highly active antiretroviral therapy.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-infected patients have weak responses to vaccines and may require revised immunization regimens. We investigated the safety and immunogenicity of 2 doses of hepatitis A virus (HAV) vaccine followed by a booster dose in HIV-infected children receiving stable highly active antiretroviral therapy.
  
  
  METHODS
  A total of 235 children with CD4+ T cell percentages > or = 20% received 2 vaccine doses 24 weeks apart, and 117 received a third vaccine dose after 104 weeks. Anti-HAV antibody titers were measured at baseline and at 32, 104, and 112 weeks after the first vaccination. Subjects with antibody titers > or = 20 mIU/mL were defined as being seropositive. High and low antibody responses were defined as titers > or = 250 and <250 mIU/mL, respectively.
  
  
  RESULTS
  Of 151 subjects who were HAV seronegative at baseline, 97% seroconverted after 2 vaccine doses, and 47% had low antibody responses. At 104 weeks, 90% of subjects had antibody titers > or = 20 mIU/mL, and those with low antibody responses were more likely to lose protective antibody titers. A third vaccine dose generated significantly higher antibody titers than those observed after the second vaccine dose. Undetectable HIV RNA at baseline was associated with higher anti-HAV antibody titers after the second vaccine dose. Antibody titers after the second and third vaccine doses were weakly correlated with CD4+ T cell percentages at the time when each vaccine dose was administered. In the 45 subjects who were HAV seropositive at baseline, responses to 2 and 3 vaccine doses were higher than those in subjects who were HAV seronegative at baseline, but the responses showed similar correlations. There were no serious adverse events associated with the vaccine.
  
  
  CONCLUSIONS
  HIV-infected children with CD4+ T cell percentages > or = 20% responded better to the HAV vaccine if they had undetectable HIV RNA. The standard 2-dose immunization regimen generated low antibody titers with limited persistence. A third vaccine dose was safe and increased the antibody titers, suggesting that an increase in immunizations may be warranted in this population.
authors.affiliation: Department of Pediatrics and Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA. adriana.weinberg@uchsc.edu
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.forename: Philimon
authors.initials: P
authors.lastname: Gona
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Nachman
authors.forename: Patricia
authors.initials: P
authors.lastname: Defechereux
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Walter
authors.initials: W
authors.lastname: Hughes
authors.forename: Diane
authors.initials: D
authors.lastname: Wara
authors.forename: Steven A
authors.initials: SA
authors.lastname: Spector
authors.forename: Jennifer
authors.initials: J
authors.lastname: Read
authors.forename: Carol
authors.initials: C
authors.lastname: Elgie
authors.forename: Marlene
authors.initials: M
authors.lastname: Cooper
authors.forename: Wayne
authors.initials: W
authors.lastname: Dankner
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D035922:Hepatitis A Antibodies / Q000097:blood*; D022362:Hepatitis A Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008297:Male
chemical_list: D035922:Hepatitis A Antibodies; D022362:Hepatitis A Vaccines