Neutralization escape in human immunodeficiency virus type 1-infected long-term nonprogressors

Neutralization-escape variants of human immunodeficiency virus type 1 (HIV- 1) were sought in persons who had persistent low virus loads and who remain ed asymptomatic for at least 12-16 years of infection without antiretrovira l therapy. Viruses were isolated from 3 persons at two or three time points during the course of infection and were assessed for neutralization by seq uential autologous serum samples. Virus neutralization was poor or undetect able with contemporaneous autologous serum but improved with later serum sa mples for each person. In particular, later isolates resisted neutralizatio n by autologous serum samples that neutralized an earlier isolate. Strain-s pecific neutralizing antibodies remained detectable for up to 4.2 years wit hout diminishing in titer. The results demonstrate that neutralization-esca pe variants arise periodically in HIV-1-infected long-term nonprogressors.