Discordant increases in CD4+ T cells in human immunodeficiency virus-infected patients experiencing virologic treatment failure:: Role of changes in thymic output and T cell death

Some patients infected with human immunodeficiency virus (HIV) who are experiencing antiretroviral treatment failure have persistent improvement in CD4(+) T cell counts despite high plasma viremia. To explore the mechanisms responsible for this phenomenon, 2 parameters influencing the dynamics of CD4(+) T cells were evaluated: death of mature CD4(+) T cells and replenishment of the CD4(+) T cell pool by the thymus. The improvement in CD4(+) T cells observed in patients with treatment failure was not correlated with spontaneous, Fas ligand-induced, or activation-induced T cell death. In contrast, a significant correlation between the improvement in CD4(+) T cell counts and thymic output, as assessed by measurement of T cell receptor excision circles, was observed. These observations suggest that increased thymic output contributes to the dissociation between CD4(+) T cell counts and viremia in patients failing antiretroviral therapy and support a model in which drug-resistant HIV strains may have reduced replication rates and pathogenicity in the thymus.