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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Interruption of antiretroviral therapy blunts but does not abrogate CD4 T-cell responses to interleukin-2 administration in HIV infected patients.

BACKGROUND: Intermittent administration of interleukin (IL)-2 to HIV infected patients leads to CD4 T-cell expansions that are associated with decreased CD4 T-cell turnover. IL-2 is under evaluation in antiretroviral therapy (ART) interruption studies, but it is unclear how the emergence of viremia may affect CD4 expansions. METHODS: CD4 T-cell responses were evaluated in 27 HIV infected patients on long-term intermittent IL-2 therapy who underwent ART interruption immediately after an IL-2 cycle ('IL-2/off') and compared with responses from a previous IL-2 cycle while on continuous ART ('IL-2/on'). Immunophenotypic analysis, including intracellular Ki67 staining, of cryopreserved peripheral blood mononuclear cells was performed. RESULTS: CD4 T-cell increases, in naive and central memory CD4 T-cell subsets, were observed in the IL-2/on (106 and 327 cells/microl, respectively) and IL-2/off (84 and 184 cells/microl, respectively) cycles 1 month following IL-2 administration. These increases were greater during the IL-2/on cycle (P = 0.05, P = 0.01, respectively). In both cycles, the change in CD4 T-cell count correlated with the change in CD4/CD25 T cells. In the IL-2/off cycle, the change in the proportion of CD4 T cells expressing Ki67 was associated with both the changes in viral load (r = 0.64, P = 0.001) and the changes in CD4 T cells (r = -0.56, P = 0.01). CONCLUSIONS: IL-2 administration followed by ART interruption led to significant, although blunted, CD4 T-cell increases. IL-2 induced CD4 T-cell increases in the setting of emergent viremia were associated with decreased CD4 T-cell activation that counteracted the viremia-induced increases in CD4 T-cell activation.[1]

References

  1. Interruption of antiretroviral therapy blunts but does not abrogate CD4 T-cell responses to interleukin-2 administration in HIV infected patients. Keh, C.E., Shen, J.M., Hahn, B., Hallahan, C.W., Rehm, C.A., Thaker, V., Wynne, S.M., Davey, R.T., Lane, H.C., Sereti, I. AIDS (2006) [Pubmed]
 
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