Emergence of autologous neutralization-resistant variants from preexisting human immunodeficiency virus (HIV) quasi species during virus rebound in HIV type 1-infected patients undergoing highly active antiretroviral therapy

Abstract

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.