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

The long-term kinetics of T cell production following highly active antiret roviral therapy (HAART) were investigated in blood and lymph node in a grou p of HIV-infected subjects at early stage of established infection and pros pectively 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 subj ects. After HAART, the total body number of proliferating CD4(+)Ki67(+) T l ymphocytes 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 fractio n of proliferating CD4 and CD8 T cells were significantly correlated with t he changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell produc tion and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell produc tion in HIV infection in the presence and/or in the absence of HAART.