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

Some patients infected with human immunodeficiency virus (HIV) who are expe riencing antiretroviral treatment failure have persistent improvement in CD 4(+) T cell counts despite high plasma viremia. To explore the mechanisms r esponsible for this phenomenon, 2 parameters influencing the dynamics of CD 4(+) T cells were evaluated: death of mature CD4(+) T cells and replenishme nt of the CD4(+) T cell pool by the thymus. The improvement in CD4(+) T cel ls observed in patients with treatment failure was not correlated with spon taneous, Fas ligand-induced, or activation-induced T cell death. In contras t, a significant correlation between the improvement in CD4(+) T cell count s and thymic output, as assessed by measurement of T cell receptor excision circles, was observed. These observations suggest that increased thymic ou tput contributes to the dissociation between CD4(+) T cell counts and virem ia in patients failing antiretroviral therapy and support a model in which drug-resistant HIV strains may have reduced replication rates and pathogeni city in the thymus.