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CROI 2007; Los Angeles, Calif.; February 25-28, 2007

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The Body Covers: The 14th Conference on Retroviruses and Opportunistic Infections
Interleukin-2 Expands Select CD4+ T-Cell Populations, but Has No Effect on HIV-Specific Immune Responses

February 26, 2007

Previous studies have shown that the use of interleukin-2 (IL-2) in HIV-infected persons on antiretroviral therapy generally increases naive and central memory CD4+ T cells. The French ANRS 119 study is a randomized trial assessing whether the use of IL-2 in treatment-naive, HIV-infected patients with a CD4+ cell count between 300 and 500 cells/mm3 can prolong the time to antiretroviral therapy initiation by preserving CD4+ cell counts.

A poster presented at the 14th Conference on Retroviruses and Opportunistic Infections summarized the findings from an immunologic substudy of ANRS 119 that evaluated the short-term effects of 4.5 million IU (International Units) of IL-2 twice daily for five days at weeks 0, 8, and 16 on T-cell populations.1 At 24 weeks, the immunologic effects of IL-2 were compared with changes in an untreated control group by examining the quantity of naive (CD45RA+CCR7+), central memory (CD45RA-CCR7+), effector memory (CD45RA-CCR7-), and effector (CD45RA+CCR7-) CD4+ and CD8+ T cells. The levels of these cells were measured using flow immunotyping, while CD4+ and CD8+ T-cell pathogen-specific responses were evaluated using interferon-gamma enzyme-linked immunospot assays.

A total of 26 patients in the IL-2 group and 24 individuals in the control group were included in the substudy analysis. The baseline CD4+ cell counts and viral loads were comparable between the two groups.


Median Baseline ValueIL-2 Group
(n = 26)
Control Group
(n = 24)
Overall CD4+ cell count (cells/mm3)375381
  • CD4+ T cells379396
  • CD8+ T cells906890
HIV RNA (log10 copies/mL)4.44.5


Use of IL-2 led to dramatic changes in immunologic cell types in comparison with no IL-2 treatment. Most notably, IL-2 resulted in a significant decrease in the HIV-specific, CD4+ T-cell response to HIV, cytomegalovirus, Epstein Barr virus and flu virus at week 24. The magnitude of response in CD4+ naive and central memory T cells was proportional to the overall gain in CD4+ T cells at week 24. In contrast, the HIV-specific, CD8+ T-cell response essentially remained unchanged from baseline to week 24 among individuals on IL-2, similar to observations made for the control group.


Median Change in Cell Count (cells/mm3)IL-2 Group
(n = 26)
Control Group
(n = 24)
CD4+ T cells+123-10
  • Naive*+19-29
  • Central memory+59-15
  • Effector memory+20+20
  • Effector-9-13
CD8+ T cells+214+93
* P = .024
P = .035


The investigators interpreted these results as showing that ongoing HIV replication did not demonstrably hamper the expected effects of IL-2 on naive or central memory T-cell homeostasis.

These results, coupled with the simian immunodeficiency virus data presented by Louis Picker that highlighted the potential key role of central memory T-cell homeostasis in the pathogenesis of AIDS,2 further raise interest in the final results of several trials that are evaluating the potential clinical benefit of IL-2 in a variety of HIV-infected populations, including ANRS 119 (treatment-naive, HIV-infected individuals), ESPRIT (HIV-infected individuals with a CD4+ cell count greater than 350 cells/mm3) and SILCAAT (HIV-infected individuals with a CD4+ cell count less than 350 cells/mm3). It is hard for me to predict the outcomes of these studies, but the results will likely determine the fate of IL-2 as an immune-based intervention in the treatment of HIV infection.

Footnotes

  1. Venet A, Gougeon M-L, Hamonic S, et al, and the ANRS 119 Interstart group. Intermittent interleukin-2 therapy induces the expansion of naive and central memory CD4 T cells and has no impact on HIV-specific T-cell responses in ART-naive HIV-infected patients: immunological substudy of the ANRS 119 Interstart Trial. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Abstract 395.

  2. Picker L. Pathogenesis of AIDS -- connecting viral replication to disease in the non-human primate model. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Abstract 14.



  
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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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