title: Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants with human immunodeficiency virus type 1 infection.
abstract: OBJECTIVE
  Heptavalent pneumococcal conjugate vaccine (PCV) has been shown to be safe and effective in healthy infants and children. However, little is known about its use in children who have human immunodeficiency virus (HIV) infection and are known to be at increased risk of developing pneumococcal infections. This study was conducted to evaluate the safety and immunogenicity of heptavalent PCV in infants with HIV infection.
  
  
  METHODS
  The Pediatric AIDS Clinical Trials Group Study 292 Team randomized infants with HIV infection 2:1 to receive heptavalent PCV or placebo in a double-blinded manner. Infants were vaccinated with 3 doses at 2-month intervals, starting at ages 56 to 180 days. A booster dose was given at 15 months of age. Immunogenicity was evaluated after the third dose of vaccine, before and after the booster dose, and at 24 months of age.
  
  
  RESULTS
  Thirty infants with HIV infection received PCV, and 15 received placebo. No differences in baseline characteristics were found across arms. Five severe acute reactions were experienced by 4 subjects: 3 in the PCV arm and 1 in the placebo arm; all occurred among subjects with symptomatic disease at study entry. No differences were found in the 2 arms with respect to the number or timing of new diagnoses through 24 months of age, including diagnoses of otitis media. However, when symptomatic subjects were examined separately, the first new diagnosis occurred more rapidly among PCV recipients. Three deaths, all judged to be unrelated to study vaccine, occurred during follow-up: 2 in the PCV arm and 1 in the placebo arm. The primary immunogenicity measures were based on composites of 4-fold changes in serotype-specific immunoglobulin G titers from preimmunization levels. We found a highly significant difference between the vaccine and placebo arms, with the PCV arm showing higher rates of response. Asymptomatic and symptomatic subjects who received PCV had similar immunologic responses for all serotypes.
  
  
  CONCLUSIONS
  This study demonstrates that heptavalent PCV was well tolerated and not associated with vaccine-associated adverse reactions. Most important, this vaccine was immunogenic in the infant with HIV infection. However, additional studies of this vaccine (or others) must pay special attention to patients with symptomatic HIV disease, as they seem to be at higher risk for adverse events to any antigen.
authors.affiliation: Department of Pediatrics, State University of New York Health Science Center at Stony Brook, Stony Brook, New York 11794, USA. sharon.nachman@stonybrook.edu
authors.forename: Sharon
authors.initials: S
authors.lastname: Nachman
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.forename: James
authors.initials: J
authors.lastname: King
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: David
authors.initials: D
authors.lastname: Margolis
authors.forename: Ann
authors.initials: A
authors.lastname: Petru
authors.forename: William
authors.initials: W
authors.lastname: Shearer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smith
authors.forename: Jack
authors.initials: J
authors.lastname: Moye
authors.forename: Suzette
authors.initials: S
authors.lastname: Blanchard
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hawkins
authors.forename: Pamela
authors.initials: P
authors.lastname: Bouquin
authors.forename: Peter
authors.initials: P
authors.lastname: Vink
authors.forename: Mindy
authors.initials: M
authors.lastname: Benson
authors.forename: Scharla
authors.initials: S
authors.lastname: Estep
authors.forename: Frank
authors.initials: F
authors.lastname: Malinoski
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007117:Immunization, Secondary; D007121:Immunocompetence; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000009:adverse effects / Q000276:immunology*; D011008:Pneumococcal Infections / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000009:adverse effects / Q000276:immunology*; D012306:Risk; D012449:Safety; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines