Most would agree that the critical deficit induced by HIV-1 is a loss of antigen-specific, CD4+ helper T cells. An absence of helper cells likely compromises defenses towards opportunistic infections and HIV-1 itself. While much effort is being given to the possibility of vaccination against HIV-1, to prevent infection at its outset, our protocols are directed to using the residual intact elements of the immune system to provide therapy for patients with ongoing infection with HIV-1. In so doing, we also hope to better understand the resistance pathways that should be elicited by vaccination. 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.

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Bagdade, John D; Jilma, Bernd; Hudgins, Lisa C et al. (2018) LpA-II:B:C:D:E: a new immunochemically-defined acute phase lipoprotein in humans. Lipids Health Dis 17:127
Butelman, Eduardo Roque; Bacciardi, Silvia; Maremmani, Angelo Giovanni Icro et al. (2017) Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity? Am J Addict 26:632-639
Ansar, Muhammad; Raza, Syed Irfan; Lee, Kwanghyuk et al. (2015) A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair. J Med Genet 52:676-80
Rosenbaum, Michael; Leibel, Rudolph L (2014) 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol 223:T83-96
Ohmatsu, Hanako; Humme, Daniel; Gulati, Nicholas et al. (2014) IL32 is progressively expressed in mycosis fungoides independent of helper T-cell 2 and helper T-cell 9 polarization. Cancer Immunol Res 2:890-900
Alemán, José O; Eusebi, Leonardo H; Ricciardiello, Luigi et al. (2014) Mechanisms of obesity-induced gastrointestinal neoplasia. Gastroenterology 146:357-373
Barbuto, Scott; Idoyaga, Juliana; Vila-Perelló, Miquel et al. (2013) Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells. Nat Chem Biol 9:250-6
Guo, Xiuyang; Dhodapkar, Kavita M (2012) Central and overlapping role of Cathepsin B and inflammasome adaptor ASC in antigen presenting function of human dendritic cells. Hum Immunol 73:871-8
Dustin, Lynn B; Charles, Edgar D (2012) Primary, post-primary and non-specific immunoglobulin M responses in HCV infection. Antivir Ther 17:1449-52
Pendyala, Swaroop; Walker, Jeanne M; Holt, Peter R (2012) A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology 142:1100-1101.e2

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