Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy

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Abstract
The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4+T lymphocytes, i.e., CD4+Ki67+T lymphocytes, was not significantly different in HIV-infected (n= 73) and HIV-negative (n= 15) subjects, whereas proliferating CD8+Ki67+T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4+Ki67+T lymphocytes increased over time and was associated with an increase of both naive and memory CD4+T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4+T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship betweenex vivomeasures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART.