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 Value||IL-2 Group|
(n = 26)
(n = 24)
|Overall CD4+ cell count (cells/mm3)||375||381|
|• CD4+ T cells||379||396|
|• CD8+ T cells||906||890|
|HIV RNA (log10 copies/mL)||4.4||4.5|
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)
(n = 24)
|CD4+ T cells||+123||-10|
|• Central memory†||+59||-15|
|• Effector memory||+20||+20|
|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.