February 6, 2001
IL-2 is a cytokine secreted by activated T lymphocytes. It regulates the proliferation and differentiation of lymphocytes, including CD4+ and CD8+ T cells. Although treatment with IL-2 can cause transient increases in HIV-1 RNA levels, clinical studies with IL-2 have revealed no long-term adverse effect on the viral load. Indeed, when interleukin is administered in the setting of maximal viral suppression induced by HAART, viral load does not change.
IL-2 therapy might help purge the host's latent viral reservoir through activation of resting lymphocytes harboring provirus, or at least that was what we thought a couple of years ago when this trial was designed.
In this study from the UCSF group, patients with acute HIV infection were randomized to receive standard HAART vs. HAART plus IL-2. IL-2 was given to patients at high doses of 7.5 million units a day for five days every six weeks for a total of six cycles. As expected, the CD4 cell count remained much higher in individuals who received the IL-2. The reservoirs of latently HIV-infected cells did not change at all with IL-2, confirming what Robert Siliciano told us yesterday in a wonderful plenary lecture, implying that this strategy does not really "flush" these reservoirs, even in the setting of acute seroconversion. In that regard, this was a negative result for the trial. There seemed to be a trend to a greater proportion of individuals with viral loads below 50 in the IL-2 group, although the sample size is really too small to tell.
The increments in CD4 T cell were both in the "naive" and in the "memory" cell compartments.
I think this approach is not very practical in "real life." There were many side effects associated with this very high dose of IL-2 and the reservoirs did not really change. It is going to be extremely difficult to demonstrate that IL-2 adds something to therapy in the setting of acute seroconversion.
However, there were many posters today about the role of interleukin in the management of HIV. The CD4 gains in the arms that include IL-2 are really impressive. If we move to a paradigm of therapy where CD4 cells are the most important criteria I think in the future IL-2 will be a very important drug in the armamentarium. We just have to learn how to use to maximize the benefit for our patients.
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