STUDY OF SUBCUTANEOUS RECOMBINANT IL-2 IN PATIENTS WITH HIV-1 INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The incomplete recovery of immune function after initiation of antiretroviral therapy among patients with advanced disease is an argument for early use of antiretroviral drugs. However, the clinical benefit of antiretroviral therapy for patients with early, asymptomatic HIV disease has not been evaluated with current clinical strategies. At this disease stage, clinicians and patients face a major dilemma since available therapies are very potent in the short-term, perhaps even for several years. However, due to toxicities and the development of drug resistance, there is substantial risk of exhaustion of available antiretroviral treatments before the time when the risk of serious opportunistic diseases is greatest. Preservation of immune function by direct expansion of CD4+ lymphocytes with interleukin-2, could represent a significant additional strategy for the management of HIV. In addition, it has recently been speculated that IL-2 in combination with potent antiretroviral therapy may be a useful approach for purging HIV from the latently infected CD4+ cells. The hypothesis being tested in ESPRIT is that intervention with IL-2 therapy in combination with antiretroviral therapy at an early stage of HIV infection (CD4+ counts greater than or equal to 300 cells/mm3) will prevent CD4+ T cell depletion and result in fewer AIDS defining illnesses than antiretroviral therapy alone. Recombinant interleukin-2 (rIL-2), with the trade name Proleukin, is a potent immunomodulator currently licensed for the treatment of metastatic natural protein exerts potent in vitro effect on cells derived from patients with HIV. Critically, IL-2 induces proliferation of T-lymphocytes and B-lymphocytes, enhances cytolytic activity against a variety of target cells and increases natural killer cell function. Initial clinical studies coupled with laboratory evaluations identified a regimen for optimal induction of CD4+ T-lymphocyte proliferation. Intermittent administration of rIL-2 to patients with HIV infection based upon a regimen delivered for five days every eight weeks has now been examined in multiple trials. These studies have revealed that this regimen gives rise to significant and sustained increases in peripheral CD4+ cell counts.