title: Progressive specific immune attrition after primary, secondary and tertiary immunizations with bacteriophage phi X174 in asymptomatic HIV-1 infected patients.
abstract: BACKGROUND
  Antibody responses to immunization are often compromised in patients infected by HIV-1, and the use of childhood immunization in affected children is controversial. We investigated whether multiple immunizations with a T cell-dependent neoantigen, bacteriophage phiX174, induce selective immune attrition and post-vaccination viremia.
  
  
  METHODS
  Seventeen asymptomatic, antiretroviral therapy-naïve HIV-1-infected patients with a CD4 cell count of 450 cells/microl or greater were immunized in 1990/1991 with three intravenous doses of bacteriophage phiX174. Group 1 received zidovudine (ZDV) during the primary and secondary immunization. Group 2 received ZDV exclusively during the tertiary immunization. Bacteriophage-specific antibodies of the IgM and IgG class, lymphocyte phenotypes (CD4+, CD8+, CD4+DR+, CD8+DR+, CD4+CD45RO+ and CD4+45RA+, CD4+CD45RO+DR+) and HIV-1 plasma viremia were measured sequentially.
  
  
  RESULTS
  In both patient groups the primary, secondary and tertiary antibody responses, as expressed by geometric mean antibody titres and IgM to IgG switch, were impaired. Booster immunizations resulted in a progressive attrition of specific antibody responses to bacteriophage. Antibodies to tetanus toxoid remained stable. The HIV-1 viral loads, which were evaluated in archived specimens from eight patients, increased after immunization but returned to baseline approximately 4 weeks later. The humoral immune attrition and increases in plasma viremia were blunted by concomitant short courses of ZDV.
  
  
  CONCLUSIONS
  Multiple boosters of immunizations in asymptomatic treatment-naive HIV-1-infected patients may result in a specific immune attrition and vaccine-induced viremia. Short-term monotherapy with ZDV may have blunted these adverse effects. Hyperimmunization of HIV-1-infected patients may be detrimental unless accompanied by antiretroviral therapy.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rubinstein
authors.forename: Y
authors.initials: Y
authors.lastname: Mizrachi
authors.forename: L
authors.initials: L
authors.lastname: Bernstein
authors.forename: J
authors.initials: J
authors.lastname: Shliozberg
authors.forename: M
authors.initials: M
authors.lastname: Golodner
authors.forename: G Q
authors.initials: GQ
authors.lastname: Liu
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D010584:Bacteriophage phi X 174 / Q000276:immunology*; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D015483:HIV Antibodies; D018894:Reverse Transcriptase Inhibitors; D014765:Viral Vaccines; D015215:Zidovudine