Immune Based Therapy: IL-2 and Other Approaches
Session Day and Time: Wednesday 1:30 - 3:30 pm
Room: Hall A
Background: Interleukin-2 (IL-2) results in sustained increases in CD4 T-cell counts in HIV-1 infected individuals. Its effect, both acutely and longer term, on T-cell activation and IL-2 receptor expression is less well described, and may impact on the efficacy of the induction/maintenance style regimens currently being used.
Methods: We performed a prospective, randomized, controlled trial of HAART ▒ IL-2 in HIV-1 infected individuals. After 16 wks of HAART eligible patients (pts) (VL BLD, CD4 ≥ 300) were randomized to receive IL-2 at 5 MU subcutaneously bd for 5 days for 3 4-weekly cycles (wks 17, 21+ 25; Group 1) or no IL-2 (Group 2). Samples were taken at wks 0, 4, 8, 16, 21, 25, 29, 41, 53, and 65 post HAART for CD4 T-cell counts and viral load. Three- (3-) color flow cytometry was performed on CD4 and CD8 T-cell subsets for na´ve/resting (CD45RA) and memory/effector cells (CD45RO), activation markers (HLA DR, CD38), co-stimulatory molecule CD28 and the α and ▀ chains of the IL-2 receptor (CD25, CD122). Receptor expression intensity was also measured. Student t-test was used to determine the mean difference between the 2 groups.
Results: Forty-one (41) pts were enrolled and 37 randomized (19 to Group 1). Fifteen (15) pts received 46 cycles of IL-2. At 65 wks, mean viral load was below the level of detection (p < 0.001) and mean CD4 T-cell count rose significantly in both groups, more so in Group 1 (p = 0.002). Both na´ve CD4 and CD8 T-cells increased to a greater degree in the IL-2 treated group. The rise in CD4 and CD8 memory cells was comparable in the two groups although the CD8+/45RO+ percentage showed a greater increase acutely in relation to IL-2 therapy. CD8+/HLA DR+ and /CD38+ cells decreased over the study period. IL-2 cycle related increases were seen but there was no difference between the groups at the end of the study. CD4+/CD25+ cells rose acutely with each IL-2 cycle, the difference between the groups was sustained (p = 0.04). No overall change in receptor expression intensity was seen. CD4+/CD122+ and CD8+/CD122+ cells also rose acutely in response to IL-2 but this was not sustained.
Conclusions: IL-2 therapy results in an acute rise in CD4+/CD25+ T-cells which is sustained. The acute rise seen in T-cell activation markers and CD4+ and CD8+/CD122+ cells is transient. These results add further support to the current approach to IL-2 therapy with a prolonged lag phase between IL-2 induction and maintenance therapy.