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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinicians have used combination antiretroviral therapy to treat HIV infection since 1996, and these drugs can produce a significant reduction in viral load as well as mitigate immune deficiency caused by HIV. For many patients, however, combination therapy fails to provide adequate immune system restoration, an important part of HIV infection management. The immune-based therapy most studied for treatment of HIV is interleukin-2 (IL-2), a cytokine licensed for the treatment of renal cell carcinoma. Chiron Corporation manufactures recombinant IL-2 under the brand name Proleukin. Characteristics and biological activity of IL-2 are detailed, along with the rationale for including the drug in anti-HIV treatments. Data from clinical trials are presented. Practical steps to diminishing toxicity of IL-2, and the controversy surrounding its approval by the U.S. Food and Drug Administration (FDA) are detailed.
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PMID:Interleukin-2 for the treatment of HIV infection. 1136 80

Despite the effectiveness of antiviral drugs, and the determination that an individual has HIV levels below the limit of detection, HIV capable of replicating may remain in a resting state in T-cells. In this resting state, neither the immune system nor HIV drugs identify these cells as infected, so they do not challenge the HIV infection. Interleukin-2 (IL-2, Proleukin) transforms resting cells into active ones, exposing HIV and the cells, which HIV drugs and the immune system can detect and combat. Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), conducted a study comparing people taking Highly Active Anti-HIV Therapy (HAART) plus IL-2 and those taking HAART alone, and found that those who also took IL-2 had no detectable HIV resting cells. Studies of IL-2 have also demonstrated significant increases in CD4+ cell counts. A trial to measure whether the increases in CD4+ counts have an effect on reducing risk of related infections is enrolling through a community based clinical trial network (CPCRA). Contact information is provided. A fact sheet is available by request through Project Inform's National HIV/AIDS Treatment Hotline.
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PMID:Interleukin-2 (IL-2): a path toward functional eradication? 1136 94

The Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) is a large ongoing randomized trial of subcutaneous interleukin-2 (IL-2) plus antiretroviral therapy versus antiretroviral therapy alone in patients with HIV (human immunodeficiency virus) disease and CD4 cell counts of at least 300 cells/mm(3). The primary objective is to determine whether the addition of IL-2 to combination antiretroviral therapy improves morbidity and mortality. The aim is to recruit 4000 participants and follow them for an average of 5 years. Eligible subjects will be recruited at 275 investigational sites in 23 countries around the world. Coupled with broad eligibility criteria this will ensure widely applicable results. A range of secondary objectives will also be addressed in this setting that will include the conduct of observational studies and nested substudies with a public health focus. This article describes the rationale supporting the trial in addition to reviewing the study design, coordination, and governance.
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PMID:The evaluation of subcutaneous proleukin (interleukin-2) in a randomized international trial: rationale, design, and methods of ESPRIT. 1194 48

A recombinant human IL-2 analog (rIL-2, Proleukin) is currently being evaluated for clinical benefit in HIV infected patients. It is approved for therapy of patients with metastatic melanoma and renal cell carcinoma. Treatment of cancer patients with rIL-2 results in durable responses but is associated with life-threatening toxicity, which limits its use to patients in relatively good health. Antitumor efficacy associated with rIL-2 therapy are hypothesized to be mediated by distinct types of cells that express structurally different forms of the IL-2 receptor. This hypothesis suggests that it might be possible to engineer an IL-2 variant addressing the risks associated with the therapeutic use of IL-2. In this article, we review the clinical experience with IL-2 and its analogs, the evidence that different IL-2 receptors may dissociate efficacy and toxicity, and describe the generation of a novel IL-2 variant with the potential for a superior therapeutic index.
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PMID:Therapeutic enhancement of IL-2 through molecular design. 1236 61

Recombinant interleukin-2 (IL-2) (aldesleukin, Proleukin, Chiron, Emeryville, CA) is approved for treatment of cancer patients and under investigation in HIV-infected individuals. However, treatment with aldesleukin is associated with toxicity, which may be due to its elicitation of inflammatory mediators from cells that express the intermediate-affinity IL-2 receptor. BAY 50-4798, a novel IL-2 analog, is a selective agonist for the high-affinity receptor. It induces the proliferation of activated T cells with a potency similar to that of aldesleukin but has reduced activity on cells expressing the intermediate-affinity receptor. In the current study, we compared cytokine responses elicited in peripheral blood mononuclear cell (PBMC) cultures stimulated with BAY 50-4798 or aldesleukin. BAY 50-4798 induced approximately 5-fold lower mean levels of endogenous IL-2 than aldesleukin, and at least 50% lower levels of proinflammatory cytokines, such as tumor necrosis fctor-alpha (TNF-alpha), IL-1beta, IL-6, and interferon-gamma (IFN-gamma). Furthermore, statistically significant reductions in the levels of IL-5, IL-8, IL-10, IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were observed in response to BAY 50-4798. These findings increase our understanding of the biologic action of BAY 50-4798 and suggest a mechanism by which it may exhibit better safety than aldesleukin in humans.
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PMID:Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. 1654 39

The 16th Conference on Retroviruses and Opportunistic Infections maintained its tradition of being recognized as the preeminent forum for detailing the state-of-the-art of antiretroviral therapy. Abundant new and updated information was presented on investigational drugs, approaches to the management of treatment-naive and -experienced patients, the use of drugs for prevention of mother-to-child HIV-1 transmission, and antiretroviral drug resistance. Of particular note were the continued advances in antiretroviral treatment and research emanating from resource-limited settings and the presentation of the results of 2 much-anticipated, phase III trials of interleukin-2, ESPRIT (Evaluation of Subcutaneous Proleukin in a Randomized International Trial) and SILCAAT (Subcutaneous, Recombinant Human Interleukin-2 in HIV-Infected Patients With Low CD4+ Counts Receiving Active Antiretroviral Therapy).
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PMID:Advances in antiretroviral therapy. 1940 9