TreatmentUpdate78 - Vol. 7, No. 8; June 1997
Sean Hosein

IL-2 (interleukin-2) is a chemical produced by the immune system which causes T cells to grow and helps them fight infections. Since production of IL-2 decreases as the immune system weakens, it is being tested in several studies to see if it can help rebuild the immune systems of PHAs. IL-2 is available in North America as a treatment for kidney cancer. Previous reports on IL-2 have appeared in several issues of TreatmentUpdate including these recent issues: 71, 72, 74, and 76.

Study details

Researchers enrolled 18 subjects (1 female, 17 male) with an average of 350 CD4+ cells for this study. Subjects used AZT with or without ddC or ddI and received various doses of IL-2 injected under the skin for 5 consecutive days every 2 months. Eventually most volunteers received 15 million international units (IUs) of IL-2 on each of the 5 days. Researchers monitored subjects for at least 1 year and 8 subjects have remained in the study for 3 years.

Results -- CD4+ cells

Eight subjects gained a minimum of 200 CD4+ cells once they started using IL-2. Another 6 subjects experienced a smaller increase in their CD4+ cell count and the remaining 4 subjects had their counts decrease. Thus, a total of 10 subjects did not have a huge increase in their CD4+ cell counts.

Why did everyone's count not rise?

There may be at least 2 explanations for this: (1) the level of HIV (viral load) and (2) the amount of damage already sustained by the immune system. On average, the group of 10 subjects who did not have a large increase in their CD4+ cell count entered the study with a relatively high viral load (44,000 copies), compared to that of the other 8 subjects (20,000 copies). Perhaps the higher viral load made an increase in the cell count more difficult.

Readers should note that two of the subjects in the group of 10 had low viral loads ("below the limit of detection," according to the researchers). Therefore, high viral load alone may not explain why all of the 10 subjects failed to have a huge increase in their CD4+ cell count. It may also have been that the immune systems of the remaining 8 subjects were less damaged and better able to respond to the injections of IL-2 than the others. Indeed, researchers noticed that those subjects who entered the study with "higher CD4+ cell counts" were more likely to experience greater increases in CD4+ levels when given IL-2, compared to other subjects who entered with relatively low cell counts.

Results -- toxicity

Side effects reported included:

* tiredness

* muscle pain

* bone/joint pain

Occasionally, low-level bone marrow as well as liver and kidney toxicity were detected by means of blood tests, but these problems were not serious enough to cause doctors to decrease the dose of IL-2. By taking drugs to reduce swelling, nausea and pain before they received each dose of IL-2, subjects were able to reduce the side effects. Use of IL-2 did not increase viral load over the long term, perhaps because the drug causes other cells of the immune system (CD8+ cells) to suppress production of HIV.

Results -- long term

Ten subjects left the study after at least 6 months; 5 for "personal reasons or to [receive] other therapies," and 5 to join another study where they received intravenous IL-2 and the protease inhibitor indinavir. Two of the 10 who left the original study eventually died from complications due to AIDS.

Of the 8 subjects who have been receiving IL-2 for 3 years, 5 have CD4+ counts ranging between 800 and 2,000 cells. The remaining three have counts between 400 to 600 cells.

Did the drug work?

Although some volunteers experienced fantastic increases in their CD4+ cell counts, researchers admit that they do not know if these extra cells will protect subjects from the life-threatening infections seen in AIDS. To be fair, this study was not designed to show if such a benefit occurred. The researchers state that they are planning a larger study in order to address this issue.

REFERENCES:

1. Meyaard L, Otto SA, Keet IPM et al. Changes in cytokine secretion patterns of CD4+ T-cell clones in Human Immunodeficiency Virus Infection. Blood 1994;84(12):4262-4268.

2. Davey RT, Chaitt DG, Piscitelli SC, et al. Subcutaneous administration of Interleukin-2 in Human Immunodeficiency Virus Type 1-infected persons. Journal of Infectious Diseases 1997;174:781-789.

3. Kinter AL, Bende SM, Hardy EC, et al. Interleukin 2 induces CD8+ T cell-mediated suppression of Human Immunodeficiency Virus replication in CD4+ T cells and this effect overrides its ability to stimulate virus expression. Proceedings of the National Academy of Sciences USA 1995;92:10985-10989.

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Copyright © 1997 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca