Alterations in T cell phenotype and human immunodeficiency virus type 1 - Specific cytotoxicity after potent antiretroviral therapy

Cytotoxic T lymphocytes (CTLs) are an important defense against human immun odeficiency virus (HIV) type 1 but ultimately fail to control infection. To determine whether more efficient sustained immunity is induced by suppress ing replication, the evolution of T cell phenotypes and HIV-specific CD8(+) lymphocytes was prospectively investigated in 41 patients initiating combi nation therapy. Suppression of viremia to <200 copies/mL was associated wit h increases in naive cells (CD45RA(+)62L(+)) and declines in activated T ce lls (CD95(+) cell counts and CD38(+) HLA-DR+). HIV-specific tetramer-staini ng CD8(+) T cells were detected in 6 of 10 HLA-A*0201-positive persons, whi ch declined in 5 with treatment. CTL precursor frequencies were markedly co nsistent before and after treatment. Eight (72%) of 11 recognized <greater than or equal to>1 immunodominant epitope, representing either a new or an increased CTL response after treatment. Thus, activated CD8(+) T cells, inc luding those recognizing immunodominant epitopes, decline with combination therapy. However, the overall level of antigen-specific cells that are capa ble of differentiating into effectors remains stable, and the recognition o f new epitopes may occur.