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.

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.

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.