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.
Keh
Chris E
CE
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Shen
Jean M
JM
Hahn
Barbara
B
Hallahan
Claire W
CW
Rehm
Catherine A
CA
Thaker
Vishakha
V
Wynne
Sarah M
SM
Davey
Richard T
RT
Lane
H Clifford
HC
Sereti
Irini
I
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000494:pharmacology*; D014766:Viremia / Q000276:immunology
D007376:Interleukin-2