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| |  Interleukin-2 Therapy Fails to Improve Outcomes in Patients on Antiretroviral Treatment: Presented at CROI By Ed Susman MONTREAL -- February 10, 2009 -- Patients with HIV who are treated with the immunomodulator cytokine interleukin-2 (IL-2) do not appear to have benefits over those treated with standard highly active antiretroviral therapy, according to an analysis of 2 large, long-term studies. In the 2 studies, which followed patients for 7 years, researchers found no significant difference in rates of death or development of opportunistic infections between patients receiving IL-2 in addition to standard therapy or those getting only standard therapy alone. "This trial provides a definitive answer about the clinical value of IL-2 among patients taking antiretroviral therapy," said Yves Levy, MD, of Hôpital Henri Mondor, Créteil, France, referring to the Subcutaneous, Recombinant, Human Interleukin-2 in HIV-Infected Patients With Low CD4+ Counts Under Active Antiretroviral Therapy (SILCAAT) trial. IL-2 therapy should not be used in patients taking antiretroviral therapy, Dr. Levy said during a press briefing on February 10 here at the 16th Conference on Retroviruses and Opportunistic Infections (CROI). Earlier at the conference, he presented his findings along with a presentation by Marcelo H. Losso, MD, Hospital José María Ramos Mejía, Buenos Aires, Argentina, of results from the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). Together, the 2 studies involved more than 5,800 HIV-infected patients in 25 countries. Participants were assigned at random to receive combination antiretroviral therapy alone or with injections of aldesleukin, a synthetic form of IL-2, over several 5-day cycles. To evaluate the effects of IL-2 treatment at different stages of HIV infection, the ESPRIT study enrolled patients with early-stage infection who had CD4-positive T-cell counts of 300 cells/mm3 or greater, while the SILCAAT study enrolled patients with later-stage HIV infection who had CD4-positive T-cell counts between 50 and 299 cells/mm3. In ESPRIT, IL-2 administration was associated with an average increase in CD4-positive cell count of 160 cells/mm3 compared with no IL-2 injections, but Dr. Losso said that difference did not translate into a significant benefit for patients. In fact, patients in this study receiving IL-2 had more grade 1 to 3 toxicities, mainly injection-site reactions, and more grade 4 adverse effects than did patients not receiving IL-2. Dr. Levy said the group receiving IL-2 in ESPRIT experienced more lower-grade adverse events, but not more serious grade 4 events, than the group that did not receive IL-2. Of the 4,111 patients in the ESPRIT study, patients in the IL-2 group experienced the primary endpoint at a rate of 1.13 events per 100 person-years compared with 1.21 per 100 person-years for patients on standard antiretroviral therapy alone (P = .52). Among the 1,695 patients enrolled in the SILCAAT study, patients on IL-2 experienced the primary endpoint at a rate of 1.92 events per 100 person-years compared with 2.12 per 100 person-years among patients on standard antiretroviral therapy alone (P = .47). "In the end, the results of these 2 studies indicate that although a person's number of CD4-positive T cells is a key measure of success in the treatment of HIV with antiretroviral drugs, we can't rely on CD4-positive T-cell counts to predict whether immune-based therapies such as IL-2 will improve the health of HIV-infected individuals," said Dr. Levy. Dr. Levy's study began in April 1999, ended in November 2008, and was conducted by the same international coordinating centre structure that conducted ESPRIT. All volunteers were assessed every 4 months for about 7 years. The 2 trials were sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Funding for ESPRIT was provided by Chiron Corp., which is part of Novartis Pharmaceuticals. Funding for SILCAAT shifted from the Chiron Corp. to NIAID's Division of Clinical Research in 2003. [Presentation title: Effect of Interleukin-2 on Clinical Outcomes in Patients With CD4+ Cell Count 50 to 299/mm3: Primary Results of the SILCAAT Study. Abstract 90bLB]
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