Bay Area Reporter - February 19, 2009
Bob Roehr

There is no benefit to the CD4 cells generated by interlukin-2 (IL-2) in treating HIV infection. The conclusive news shocked researchers when trial results were unblinded in January. They were presented for the first time last week at the Conference on Retroviruses and Opportunistic Infections in Montreal.

Small, early trials of IL-2, a natural cytokine or chemical modulator of immune function, had dramatically expanded the number of CD4 cells in patients who received it. However, many patients experienced flu-like symptoms associated with IL-2, and other side effects.

A pair of clinical trials was created about a decade ago to answer the question of whether or not the increased number of CD4 cells delayed disease or death. The ESPRIT trial enrolled patients with more than 300 CD4 cells and the SILCAAT trial those with fewer than 300 CD4 cells.

The huge trials, 4,111 patients in 25 countries and 1,695 patients in 11 countries respectively, randomized patients to receive highly active antiretroviral therapy alone or HAART with IL-2. Cycles of the cytokine were administered to maintain CD4 count above twice what the patient started with, or above 1,000. Patients were followed for more than seven years.

CD4 counts increased in both groups in the study, due to the effect of HAART, which allowed the immune system to reconstitute itself to some extent, said ESPRIT principal investigator Donald Abrams, from the University of California, San Francisco. "However, at all times there was a significant gradient between the two" groups of about 160 cells.

But in the end it didn't make any difference, regardless of how they analyzed the data. "The consistency of the finds are quite compelling," he said.

Abrams said possible explanations are that "the CD4 cells expanded by IL-2 are not functionally equivalent to the CD4 cells arising as a result of viral load suppression with HAART." Or it could be that IL-2 also generates harmful effects through other pathways, which cancel out the benefits.

He suggested that CD4 "may not be a reliable surrogate marker for clinical outcomes in the evaluation of immune-based therapies."

The National Institutes of Health has stopped other ongoing trials of IL-2.

Not everyone is convinced that this is the end of the road for IL-2. Dr. Daniel Kuritzkes, at Brigham and Women's Hospital in Boston, suggested, "In the context of a high level of viral suppression, the difference in CD4 cells simply makes no clinical difference."

On the Net: CROI 2009
Effect of Interleukin-2 on Clinical Outcomes in Patients with a CD4+ Cell Count of 300/mm3: Primary Results of the ESPRIT Study
Effect of Interleukin-2 on Clinical Outcomes in Patients with CD4+ Cell Count 50 to 299/mm3: Primary Results of the SILCAAT Study

090219
BR090206

Copyright © 2009 - The Bay Area Reporter. Reproduction of this article (other than one copy for personal reference) must be cleared through the The Bay Area Reporter.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Elton John AIDS Foundation UK, the National Library of Medicine, AIDS Walk of Orange County, and donations from users like you.

Always watch for outdated information. This article first appeared in 2009. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2009. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .