• Prospective, Randomized, Controlled Phase II Study of Highly Active Antiretroviral Therapy (HAART) with Continuous IV (CIV) or Subcutaneous (SC) Interleukin-2 (IL-2) in HIV-Infected Patients with CD4+Counts of 50 -- 350 cells/mm³: ACTG 328 -- Final Results at 84 Weeks (Slide Session 17)
  Authored by R. Mitsuyasu, R. Pollard, R. Gelman, and D. Weng for the ACTG 328 Protocol Team
  View the original abstract

It has been known for over a decade now that the drug interleukin 2, or IL-2, is able to increase the number of circulating CD4 cells. While the use of antivirals also usually results in an increase in the number of these cells, it is clear that this boost can be improved by the use of IL-2. This study sought to define the size of the increase for those perhaps most in need for this boost -- people with a CD4 count between 50 and 350. The design was a randomized trial comparing standard antiviral treatment to either intravenous or subcutaneous IL-2, either given for five days every eight weeks.

At the onset of the study, the average CD4 count was about 300 cells. After about a year, the average increase was about 100 cells in the group who received only antivirals, but there was an average 240-cell increase in the group who got subcutaneous IL-2 and an average 309-cell increase in the group who received IV IL-2. Statistically, these changes were significantly different from the antiviral-only group. While these are averages of changes, it was noted by the presenter that the improvement in CD4 counts was less for those who started with the lowest counts, although this was not reported in any detail. There were no reported changes in the CD8 cells, nor was there any clear change in the skin test response of those who received IL-2 versus antivirals alone.

IL-2 is noted as being a drug with some important side effects that are a consideration for anyone thinking about this treatment. However, 70% of the people in this study completed all six cycles during the year of treatment, but most of those who started on IV IL-2 did switch over to subcutaneous IL-2. The predicted side effects, mainly a flu-like illness with nausea, vomiting, fatigue, fevers, and malaise were all seen as expected in this study. Despite this, at the end of the study the group who received subcutaneous IL-2 reported an improvement in their overall quality of life and their scores were higher than those who took only antivirals.

There are now some very large international trials ongoing that will attempt to better define whether the improvement in CD4 counts actually results in a decreased risk of HIV-related illnesses. The appropriate use of IL-2 still remains undefined, since it remains unproven if the increases in these cell counts actually results in a decrease in risk of illness. Studies are also underway to evaluate the use of IL-2 at higher CD4 counts. Nonetheless, IL-2 studies for those with lower CD4 counts are still needed. It is clear that for some people, immune reconstitution with antivirals alone has been less than what is needed and does not ensure that the risk of illness will be decreased for the years to come.