ESPRIT reports substantial CD4 rises as enrollment passes 2,500

Preliminary data from the ongoing international ESPRIT trial show significant increases in CD4 counts amongst interleukin-2 (IL-2) recipients following three IL-2 cycles. The report coincides with the news that enrollment into this important study has now passed 2,500 patients.

ESPRIT is a multicentre, Phase III, open-label trial designed to assess the effect of subcutaneous IL-2 on HIV disease progression in people receiving antiretroviral therapy, with CD4 counts over 300. Planned to recruit 4,000 people in total, ESPRIT randomises participants to receive or not receive IL-2 over a five year follow-up period. The trial, which began recruitment in October 2000, is one of a small but expanding number of large HIV therapy trials which are focussed on clinical endpoints, such as the development of new AIDS-defining events, rather than solely on changes in viral load and CD4 counts, themselves surrogate markers for these so-called ‘harder’ clinical events. The launch of the SMART study, another clinical endpoint trial, designed to investigate deferral of antiretroviral therapy, was recently reported here at aidsmap.com. IL-2, an immune therapy rather than an antiretroviral, has a well-documented boosting effect on CD4. Whether this increase in CD4 cells will translate into better health and survival over the longer-term, is the question ESPRIT is set up to answer.

Ann Labriola and colleagues reported on ESPRIT’s progress so far at the Ninth Retroviruses Conference in Seattle on Monday. The analysis included those 396 participants who have received three cycles of IL-2 over a period of eight months. Mean CD4 at entry was 547 cells in this group, and the mean nadir – the lowest CD4 count ever recorded – was 274 cells. Participants had received antiretroviral therapy for an average of 4.7 years, and 71.6% had viral load below 500 copies.

As reported previously at last summer’s International AIDS Society conference in Buenos Aires, treatment will IL-2 produced substantial increases in CD4. The mean increase after three cycles was 326 cells. Indeed, significant rises were observed across the range of demographic characteristics. For example, and importantly, in those participants who had a nadir CD4 count below 100 – the group whose immune repertoire has been most compromised – the mean CD4 cell rise was 256 cells.

The objective of the current analysis was to identify predictors of CD4 cell count response. The strongest predictor was the CD4 nadir – the higher the nadir, the larger the rise in CD4 count on IL-2. Duration of antiretroviral therapy appeared to be associated with the degree of CD4 response, but this was a trend which did not reach significance.

ESPRIT continues to recruit participants at sites in Europe, North America, Australia, Argentina, Israel and Thailand. Details of the trial protocol and of participating UK sites are available here at aidsmap.com. For sites elsewhere see the ESPRIT website. More information on the use of IL-2 in HIV infection, its administration and side-effects, can also be found on this site by taking this link.