title: Immunogenicity, safety, and predictors of response after a pneumococcal conjugate and pneumococcal polysaccharide vaccine series in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy.
abstract: BACKGROUND
  The immunogenicity and safety of 2 doses of pneumococcal conjugate vaccine (PCV) and 1 dose of pneumococcal polysaccharide vaccine (PPV) were evaluated in human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART).
  
  
  METHODS
  Children 2 to <19 years, receiving stable HAART for > or =3-6 months, with HIV RNA PCR <30,000-60,000 copies/mL, received 2 doses of PCV and 1 dose of PPV at sequential 8-week intervals. Antibodies to pneumococcal serotypes (STs) 1 (PPV only) and 6B, 14, 19F, and 23F (PCV and PPV) were measured by ELISA.
  
  
  RESULTS
  Two hundred sixty-three subjects were enrolled, of whom 225 met criteria for inclusion in the primary dataset. Antibody concentrations were low at entry, despite previous PPV in 75%. After vaccination, 76%-96% had concentrations > or =0.5 microg/mL and 62-88% > or =1.0 microg/mL to the 5 STs (geometric mean concentrations [GMCs] = 1.44-4.25 microg/mL). Incremental gains in antibody concentration occurred with each vaccine dose. Predictors of response included higher antibody concentration at entry, higher immune stratum (based on nadir CD4% before HAART and CD4% at screening), lower entry viral RNA, longer duration of the entry HAART regimen, and age <7 years. Response was more consistently related to screening CD4% than nadir CD4%. Seven percent had vaccine-related grade 3 events, most of which were local reactions.
  
  
  CONCLUSIONS
  Two PCVs and 1 PPV were immunogenic and safe in HIV-infected children 2 to <19 years who were receiving HAART. Responses were suggestive of functional immune reconstitution. Immunologic status based on nadir and, especially, current CD4% and control of HIV viremia were independent determinants of response.
authors.affiliation: University of Colorado School of Medicine, Pediatric Infectious Disease, The Children's Hospital, Denver, CO 80218, USA. abzug.mark@tchden.org
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Abzug
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Pelton
authors.forename: Lin-Ye
authors.initials: LY
authors.lastname: Song
authors.forename: Terence
authors.initials: T
authors.lastname: Fenton
authors.forename: Myron J
authors.initials: MJ
authors.lastname: Levin
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Nachman
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.forename: Howard M
authors.initials: HM
authors.lastname: Rosenblatt
authors.forename: John F
authors.initials: JF
authors.lastname: Marcinak
authors.forename: Arry
authors.initials: A
authors.lastname: Dieudonne
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: Indu
authors.initials: I
authors.lastname: Pathak
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D013223:Statistics as Topic; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D012367:RNA, Viral