Ronald T. Mitsuyasu, M.D., is the Principal Investigator for the UCLA ACTU (University of California, Los Angeles; AIDS Clinical Trials Unit). Dan Dunable interviewed Dr. Mitsuyasu via e-mail prior to a community luncheon held at ASP in April, where Dr. Mitsuyasu discussed the use of Interleukin-2 (IL-2) in people living with HIV to help boost T-cells and possibly give their antiretroviral regimens increased effectiveness.
Dan Dunable: Dr. Mitsuyasu, could you explain what Interleukin-2 is, and what its effect is on the immune system of someone living with HIV?
Ronald T. Mitsuyasu, MD: IL-2 is a T-cell growth factor, produced by immune cells, which stimulates the growth and differentiation of T lymphocytes. In addition, it enhances the function of T-cells, thus potentiating the immune response in individuals with HIV or cancer. In most patients with HIV who are on fully suppressive antiretroviral therapy, IL-2 can increase the number of CD4 cells and increase their function.
DD: Have you found the CD4+ and CD8+ levels that do increase during administration of IL-2 remain high, or do they tend to decrease after discontinuation of IL-2?
RM: Once the target T-cell count has been reached, the frequency of IL-2 administration can be decreased to once every few months (rather than every eight weeks) and still maintain the higher T cell count. The studies done with IL-2 have shown a gradual increase in the CD4 count measured just prior to each subsequent dose of IL-2.
DD: What answers do you hope to find from the SILCAAT and Esprit studies?
RM: These studies are clinical efficacy studies. Thus they are designed to see if IL-2 will improve the clinical outcome of patients who receive it. Specifically, the studies are seeking to demonstrate whether IL-2 can delay the time to AIDS defining illnesses of death in patients who get this treatment with HAART vs. those who get HAART alone. SILCAAT is targeted at patients with CD4 counts 50 to 300, and Esprit at those with CD4 >300.
DD: There has been a fear among many people living with HIV/AIDS that IL-2 will raise their viral load. Have you found this to be the case?
RM: In every study in which IL-2 has been given to patients with undetectable viral load on HAART, no increase in HIV viral load has been seen with IL-2. This now exceeds 10 studies in which no change in HIV RNA has been seen with IL-2.
DD: How is IL-2 generally administered, and what is the recommended dosing? Does it need to be refrigerated?
RM: IL-2 is typically given by injection under the skin (subcutaneous injections) at a dose of 4.5 to 7.5 million units twice a day for five days, repeated every eight weeks. Other regimens include a lower dose 1 to 2 million units given continuously by single daily injection. We no longer need to give IL-2 by intravenous infusion as was once necessary.
DD: Do you have any thoughts on every-day injections of low dose IL-2, such as that used in the small study reported on at ICAAC by Kendall A. Smith, MD?
RM: In general, the low dose, single dose IL-2 studies have not shown as frequent or as dramatic increases in CD4 counts as has been seen with the intermittent dose schedule. Low continuous dose IL-2 is expected to give greater increase in NK cells as opposed to higher T-cell increases with intermittent dosing schedules.
DD: Side effects have been a concern with the use of IL-2 in previous studies. Have the side effects become less severe, and do you have any suggestions for managing those side effects?
RM: Side effects appear to be less with lower doses of IL-2. Major side effects are flu like symptoms of fatigue, malaise, low grade fever, skin rash and muscle aches. These side effects can be managed with pre-medication with Tylenol and Benadryl, and adjustment of dosage as needed.
DD: What are your thoughts on the use of IL-2 to flush out HIV from the reservoirs where it seems to hide in the body?
RM: This hypothesis still needs to be tested in clinical trials.
DD: Are there any other comments you would like to make to those people considering enrolling in either SILCAAT or Esprit studies?
RM: I believe it is only through careful clinical trials research that we will be able to determine if IL-2 has any direct benefit to patients with HIV. Since the drug is not without side effects we must have clear evidence of its usefulness before using it routinely in patients. These studies are the best way to answer important questions about the role of IL-2 in HIV patients and will also allow patients to receive this drug while being carefully monitored and at no cost to them.
DD: Dr. Mitsuyasu, thank you for your time with these questions, and thank you in advance for coming to Atlanta.
For more information on the SILCAAT study in the Atlanta area, contact Beverly at the AIDS Research Consortium of Atlanta (ARCA) at 404-876-2317, ext. 331. Nationally, you can contact the manufacturer Chiron, at 1-800-CHIRON8, or through their website: www.silcaat.com.