Progressive specific immune attrition after primary, secondary and tertiary immunizations with bacteriophage Phi X174 in asymptomatic HIV-1 infected patients

Background: Antibody responses to immunization are often compromised in pat ients infected by HIV-1, and the use of childhood immunization in affected children is controversial. We investigated whether multiple immunizations w ith a T cell-depen dent neoantigen, bacteriophage Phi X174, induce selectiv e immune attrition and postvaccination viremia. Methods: Seventeen asymptomatic, antiretroviral therapy-naive HIV-1-infecte d patients with a CD4 cell count of 450 cells/mu l or greater were immunize d in 1990/1991 with three intravenous doses of bacteriophage Phi X174. Grou p 1 received zidovudine (ZDV) during the primary and secondary immunization . Group 2 received ZDV exclusively during the tertiary immunization. Bacter iophage-specific antibodies of the IgM and Ige class, lymphocyte phenotypes (CD4(+), CD8(+), CD4+DR+, CD8+DR+, CD4+CD45RO+ and CD4+45RA+, CD4+CD45RO+D R+) and HIV-1 plasma viremia were measured sequentially. Results: In both patient groups the primary, secondary and tertiary antibod y responses, as expressed by geometric mean antibody titres and IgM to IgG switch, were impaired. Booster immunizations resulted in a progressive attr ition of specific antibody responses to bacteriophage. Antibodies to tetanu s toroid remained stable. The HIV-1 viral loads, which were evaluated in ar chived specimens from eight patients, increased after immunization but retu rned to baseline appoximately 4 weeks later. The humoral immune attrition a nd increases in plasma viremia were blunted by concomitant short courses of ZDV. Discussion: Multiple boosters of immunizations in asymptomatic treatment-na ive HIV-l-infected patients may result in a specific immune attrition and v accine-induced viremia. Short-term monotherapy with ZDV may have blunted th ese adverse effects. Hyperimmunization of HIV-1-infected patients may be de trimental unless accompanied by antiretroviral therapy. (C) 2000 Lippincott Williams & Wilkins.