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 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 between ex vivo measures 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.
Fleury
S
S
Laboratory of AIDS Immunopathogenesis, Department of Medicine, Divisions of Infection Diseases and of Immunology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
Rizzardi
G P
GP
Chapuis
A
A
Tambussi
G
G
Knabenhans
C
C
Simeoni
E
E
Meuwly
J Y
JY
Corpataux
J M
JM
Lazzarin
A
A
Miedema
F
F
Pantaleo
G
G
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D019888:Nelfinavir / Q000627:therapeutic use; D012044:Regression Analysis; D019258:Saquinavir / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D019888:Nelfinavir; D019258:Saquinavir; D000099227:Abacavir