First results from ESPRIT study: CD4 response to IL-2 is associated with higher nadir and baseline CD4 and younger age

Preliminary results of the multinational ESPRIT (Evaluation of Subcutaneous Proleukin in a Randomised International Trial) showed that CD4 cell count response after the first three cycles of IL-2, used in addition to HAART in patients with baseline CD4 counts >300 cells/ml, at month eight, is associated with higher nadir CD4 count, higher baseline CD4 and younger age.

Of the 1,142 patients who completed three cycles of IL-2 by month eight, 9% were classified as ‘non-responders’ because they had CD4 counts below their baseline values. There were 4.6% who had a small increase of less than 50 cells/mm3, and 22.4% who had an increase of between 51 and 200 cells/mm3. The remaining participants, almost 70%, were classified as ‘responders’ because they had an increase of at least 200 cells/mm3 but 27% did not reach the predefined primary endpoint goal, defined as a doubling of the baseline CD4 count or reaching 1,000 cells/mm3 (whichever is lower) and 36% did.

The following factors were associated with CD4 response (>200 cell/mm3 increase or above CD4 goal at eight months): higher nadir CD4 (P<0.001), higher baseline CD4 (P=0.02), and younger age (P=0.03). Odds of response increased by 28% and 11% respectively, for a higher nadir and baseline CD4 count of 100 cells/mm3, and by 19% for 10-year younger age. There was no evidence of an association with viral load <500 copies/ml, hepatitis C or B status, time on antiretroviral therapy, prior progression of disease or gender

Ref: Weiss L, Aboulhab J, Babiker GA et al. Preliminary results of ESPRIT (Evaluation of Subcutaneous Proleukin in a Randomised International Trial): baseline predictors of CD4 T-cell response to Interleukin-2. 2nd IAS Conference on HIV Pathogenesis and Treatment, 13-16 July 2003, Paris. Abstract 13.

Comment

Results from this large international study, which has recruited almost 4,000 patients and will follow them for five years, provides evidence that IL-2 can significantly boost CD4 levels in a majority of patients.

It is a concern that almost 10% of patients saw their CD4 count drop and 5% had an increase of less than 50 cells/mm3 given that these patients are also on background HAART regimens, and also given the significant side effects associated with the weeks when IL-2 is taken.

Data were not presented from the control arm of the study randomised to continue HAART without IL-2.