Background:  Of patients with advanced HIV infection who begin HAART, 5 to 10% experience a poor immune response despite persistent viral suppression and remain with low CD4⁺ lymphocyte counts. We studied the safety and long-term efficacy of subcutaneous recombinant interleukin-2 (rIL-2) in patients with blunted immune response to HAART despite viral suppression to undetectable levels.

Methods:  Patients were included if they were on stable HAART, had HIV-ARN <50 copies/mL and had CD4 <200 cells/mm³ without significant increase over the last 12 months. Patients were scheduled to receive 6 cycles of 4.5 x 10⁶ IU subcutaneously daily for 5 consecutive days, every 4 weeks. The primary endpoint was the median change in CD4⁺ lymphocyte counts. The non-parametric paired Wilcoxon signed-rank test was used to assess whether changes over time were different from 0.

Results:  Between January 2001 and June 2003, 19 patients were included. Median age was 43 years (range, 27 to 58), 79% were male, 64% had had a previous AIDS-defining event. The patients had been on HAART for a median of 56.5 months. Median nadir and baseline CD4⁺ cell counts were, respectively, 36/mm³ (range, 3 to 90) and 99 /mm³ (range, 15 to 198); 100% had HIV RNA <50 copies/mL. Of these, 3 discontinued treatment because of intolerance, but only 1 suffered grade 3 or 4 side effects. None suffered viral failure or an AIDS-defining event. CD4⁺ T-cell counts steadily increased to 147 cells/mm³ (range, 24 to 383) 1 month after the end of treatment (p = 0.002), and to 180 cells/mm3 (range, 36 to 280) 18 months after rIL-2 interruption. This increase involved both naïve and memory cells, and was associated with a significant decrease in the expression rates of activation markers (HLA-DR and CD38) on both CD4⁺ and CD8⁺ T cells. Furthermore, there was an increase in the expression rates of the a-chain of IL-2 receptor (CD25) on CD4⁺ T-cells (p = 0.008) and in the intracellular production of IL-2 in both CD4 and CD8 T cells.

Conclusion:  rIL-2 might be useful in patients with advanced HIV disease showing a blunted immune response to HAART. Our results suggest that rIL-2 leads to the emergence of a CD4⁺CD25⁺ T-cell subpopulation that plays an essential role in the homeostasis of the peripheral CD4 T cell pool, with down-regulation of immune activation alongside with the increase in the counts of naïve and recall memory.