IMMUNOMODULATION OF HIV 1 INFECTED PATIENTS WITH RIL 2

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This protocol continues prior work that IL-2 can energize the patient's immune system. IL-2 is one of the key products that is made by the missing CD4+ helper T cells. However: a) IL-2 has been toxic in other circumstances, especially tumor therapy. Prior toxicities were most likely due to the very high doses that were used, and possibly the intravenous route. We have used lower doses intracutaneously and have encountered minimal toxicities in our two studies to date. b) By acting as a T cell growth factor, IL-2 may activate HIV-1. Such activation has been seen clinically with very high doses of IL-2. Possibly the IL-2 triggers TNF release from NK cells, and the TNF activates transcription of HIV-1. However, we have yet to see significant changes in viral burden in our patients. Only 1/9 patients showed some rise in plasma viremia by bDNA assay, and none showed an increase by amplifying gag containing sequences in semi-quantitative PCR. Nevertheless, our patients have been maintained on anti-viral therapy (AZT), and we will continue to monitor viral burdens. The rationale of the current proposal is to have patients self-administer recombinant IL-2 via the subcutaneous route, much like a diabetic takes insulin. It is already evident that this will activate certain aspects of the patient's immune system, particularly cells called "lymphokine activated killers" and "natural killers". The goal now is to document increased resistance to HIV-1 itself particularly at the level of decreased burdens of infectious virus, and increased levels of virus- specific killer cells. There is an intriguing alternative, i.e., that IL-2 will not lead to a decrease in viral burdens, but by raising CD4+ T cell counts, will provide the patient with resistance to opportunistic infection and hence a greatly improved quality of life. The ability of IL-2 to increase the number of CD4+ T cells has become apparent in recent studies from several Labs, including our own in this protocol.