Longitudinal changes in neutralizing antibody responses against autologous human immunodeficiency virus (HIV) type 1 were investigated in 19 chronically infected patients who were undergoing highly active antiretroviral therapy (HAART). Reconstitution of or increase in neutralization activity was observed in 4 of 19 patients during HAART, but neutralization activity was more or less unchanged in most patients. Three of 4 patients with increased neutralization activity had low-level viral rebound ("blips") during HAART. No correlation was found between neutralization activity and HIV-specific CD4+ T cell frequencies. There was a correlation between neutralization activity and CD4+ T cell counts. The reconstituted antibody represented limited cross-reactivity, compared with that of preexisting antibody. Binding activity to monomeric gp120, V2, and V3 peptides was reduced. Both prolonged virus suppression, for CD4+ T cell recovery, and blips, for stimulation of the immune system in vivo, may be required for development of neutralizing antibody in vivo.

The role of neutralizing antibodies (NAbs) during virus rebound in human immunodeficiency virus type 1 (HIV-1)-infected patients undergoing highly active antiretroviral therapy is poorly understood. Three patients in this study had NAbs to preexisting autologous HIV-1 and an episode of virus rebound after a prolonged period of virus suppression. To investigate the influence of NAbs on virus evolution, envelope genotypes of preexisting and rebound viruses were examined. Phylogenetic analysis of env (V1-V5) sequences indicated that rebound viruses had evolved from or preexisted in baseline populations. By use of envelope pseudotype viruses, rebound viruses were found to be significantly resistant to neutralization by autologous antibody in all 3 patients, indicating that rebound viruses were selected by NAbs. The site responsible for conferring neutralization resistance against autologous antibody was identified in the upstream C3 region in 2 of 3 patients.