Evolution of envelope sequences of human immunodeficiency virus type 1 in cellular reservoirs in the setting of potent antiviral therapy

In human immunodeficiency virus (HIV)-infected patients treated with potent antiretroviral therapy, the persistence of latently infected cells may ref lect the long decay half-life of this cellular reservoir or ongoing viral r eplication at low levels with continuous replenishment of the population or both. To address these possibilities, sequences encompassing the C2 and V3 domains of HIV-1 env were analyzed from virus present in baseline plasma a nd from viral isolates obtained after 2 years of suppressive therapy in six patients, The presence of sequence changes consistent with evolution was d emonstrated for three subjects and correlated with less complete suppressio n of viral replication, as indicated by the rapidity of the initial virus l oad decline or the intermittent reappearance of even low levels of detectab le viremia. Together, these results provide evidence for ongoing replicatio n. In the remaining three patients, virus recovered after 2 years of therap y was either genotypically contemporary with or ancestral to virus present in plasma 2 years before, indicating that virus recovery had indeed resulte d from activation of latently infected cells.