• Prediction of CD4+Cell Response to Subcutaneous Recombinant Interleukin-2 (SCrIL-2) (Poster 343)
  Authored by N. Markowitz, J. Bebchuk, E. Denning, and D. Abrams
  View the original abstract

The effectiveness of interleukin-2 (IL-2) in increasing CD4+ cell counts varies from patient to patient. Factors that cause that variance have not been well defined, but there have been some indications from past studies that it is at least partly due to the patients underlying immune function. This study explored the causes for poor response to IL-2 therapy.

CPCRA 059 was a multicenter, open-label trial in which 256 HIV-infected patients with CD4+ cell counts of 300 cells/mL or greater on antiretroviral therapy were randomized to receive subcutaneous IL-2 at 7.5 or 4.5 MIU BID. The IL-2 was given for five consecutive days every eight weeks for at least three cycles. A stratified analysis of covariance was used to compare CD4+ cell count change from baseline to day 29 of cycle 3 and to month 12.

Of the 256 patients enrolled in the study, 192 patients completed at least three cycles of IL-2 therapy and 245 had a month 12 CD4+ cell count. These patients had a mean time on antiretrovirals of 42.2 months. Median pre-enrollment nadir and baseline CD4+ cell counts were 293 cells/mL and 538 cells/mL, respectively.

The strongest predictor of CD4+ cell change from baseline to month 12 was nadir CD4+ cell count, with higher CD4+ cell count patients doing significantly better. Although no specific breakpoint for CD4+ cell count could be identified, a wide separation in response was seen between patients who had nadir CD4+ cell counts greater than 400 cells/mL and less than 400 cells/mL. Further, for those patients who completed more than three cycles of IL-2, nadir CD4+ cell count and body mass index were the strongest predictors of CD4+ cell response. Baseline CD4+ count had no significant effect on the response to IL-2.

These findings indicate the risk that is taken when therapy is delayed too long. Permanent immune system damage may result and may blunt the response to antiretrovirals and other adjunctive agents, such as IL-2. Further, these findings indicate that careful attention should be paid to the dosing requirements for IL-2 and, if further studies bear out the findings of this study, consideration should be given to using body mass index to adjust doses of IL-2.