Interleukin-2: Very Promising Results From a Preliminary Study

Interleukin-2: Very Promising Results From a Preliminary Study

Seattle Treatment Education Project (STEP) Perspective, Vol. 7, No. 1 - Spring 1995; A Publication of the Seattle Treat- ment Education Project, 127 Broadway E. Ste. 200, Seattle, WA 98102 * (206) 329-4857. Published 3 times a year
Jeffrey T. Schouten, MD

The most significant study to date of intravenous interleukin-2 used to treat HIV infection was reported in the New England Journal of Medicine on March 2, 1994.1 The report received widespread media coverage due to the dramatic increases seen in CD4 cell counts in some people who received intravenous interleukin-2. For an in depth discussion of interleukin-2, please refer to the STEP Fact Sheet at the end of this report. The study was conducted by the National Institute of Allergy and Infectious Diseases. Two groups were studied, 23 participants with CD4 counts above 200 received inpatient infusions of interleukin-2 at doses ranging from 1.8 million to 24 million international units (IU) per day, in a continuos infusion via a central venous line over 5 days or 21 days. All of the people in the study were on antiretroviral therapy (mostly AZT) prior to and during the interleukin-2 infusion study. The second group in the study consisted of 100 people with CD4 counts above 200 who received 5 day infusions of interleukin-2 every 8 weeks at a starting dose of 1.8 million IU per day. Following the initial study, 15 people with CD4 counts below 200 were enrolled in this study. Again, all of these people were also on an antiretroviral, either AZT, ddI, and/or ddC.

The first part of the study evaluated increasing doses of interleukin-2. The maximal dose tolerated was 12 million IU per day over 21 days, and 18 million IU per day over 5 days. The majority of participants experienced significant side effects, including rash, fatigue, muscle and joint pain, lowering of blood calcium level, and diffuse body swelling (capillary leak syndrome).

The most significant benefits of interleukin-2 were seen in persons with CD4 counts above 200. In 60% (6/10) of individuals treated with 4 to 13 five-day courses, CD4 counts increased over 50%. This increase was seen over a broad range of CD4 cell types, not just one group of CD4 cells. A few participants had increases in CD4 cells of over 2,000. The researchers also studied viral burden (levels of virus in the blood) by the branched-DNA assay, which measures viral RNA levels. A major concern in the use of interleukin-2 is that it may increase CD4 cells infected with HIV and result in increased levels of HIV production as the CD4 cell population expands. In 4 of the 10 patients, transient increases in viral RNA were measured, but the values returned to baseline the next time they were measured.

Unfortunately, individuals with CD4 counts below 200, who received between 2 to 5 courses of interleukin-2, experienced greater toxicity and less benefit from interleukin-2 infusions. None of the individuals with CD4 counts below 100 (6) had increases in CD4 cells, but 2 of the 6 participants with CD4 counts between 100 and 200 had an increase in CD4 count over 50%.

The authors emphasize that this study is only a "preliminary observation." The benefits of interleukin-2 infusions were restricted to patients with low viral levels and CD4 counts above 200. This is a short-term study and no long term results concerning survival differences and toxicity are available. However, the benefits of the treatment lasted up to eight months in some participants following the completion of the study, and reinfusion resulted in further increases in CD4 counts in some people. The increases observed in this study were greater than those reported in earlier trials of interleukin-2 administered subcutaneously in lower doses, so it appears that dose and delivery mechanisms are important factors to consider in future trials.

Lastly, the authors also emphasized that interleukin-2 did cause some transient increases in HIV replication in some people in this study (and all participants were receiving antiretrovirals). Because interleukin-2 may be available through some buyer's clubs, it is very important that anyone taking interleukin-2 also considering taking an antiretroviral.

Jeffrey Schouten is a general surgeon and co-chair of STEP's Scientific Review Committee.

Copyright (c) 1995 - STEP Perspectives. Noncommercial reproduction encouraged. DISTRIBUTED BY AEGIS/Seattle.
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Copyright © 1995 - Seattle Treatment Education Project (STEP) - All rights reserved. Noncommercial reproduction is encouraged. STEP is published four times a year by the Seattle Treatment Education Project, 127 Broadway East, 3rd Floor, Seattle, WA 98102. Email: step100@aol.com STEP web page

This information is designed to support, not replace, the relationship that exists between you and your doctor.
©1995. AEGIS.