Browsing by Subject "HIV"
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Item Anti-retroviral therapy of HIV infection(2001-03-15) Keiser, PhilipItem Assessing the Efficacy of Interleukin-7 as an Immunotherapeutic in the SIV+ Rhesus Macaque Model(2010-01-12) Leone, Amanda Kathleen; Sodora, Donald L.Human Immunodeficiency Virus (HIV) infection is known for depleting ‘helper’ CD4+ T cells. Highly active antiretroviral therapy (HAART) reduces viremia and increases CD4+ levels, however, 5-20% of patients fail to reconstitute CD4+ T cell levels despite viral suppression. Interluekin-7 (IL-7), a homeostatic cytokine, increases proliferation and survival of memory T cells. It is also a candidate immune therapeutic to assist CD4+ T cell recovery following HIV infection. Simian immunodeficiency virus (SIV) infection of Rhesus macaques, mimics the disease course of HIV patients and has been used to study HIV pathogenesis and treatment. The goal of this dissertation was to identify a strategy for administering IL-7 to SIV+ anti-retroviral therapy (ART) treated macaques to increase CD4+ T cell levels long-term. Glycosylated recombinant macaque IL-7 was given subcutaneously at 7 day to 6-week intervals. Proliferation, and levels, of naïve and memory CD4+ T cells, as well as other immune cell subsets were assessed. Irrespective of the dosing interval tested IL-7 transiently increased proliferation of memory and naïve cells, in CD4+ and CD8+ subsets without increasing plasma SIV titers. CD4+ T cells proliferated following each IL-7 administration at 6-week intervals, but absolute levels increased only transiently. In contrast, a frequent IL-7 dosing regimen (weekly x 3, with 2 weeks rest repeated twice) induced a single proliferative burst in CD4+ T cells but T cell levels were increased >112 days post IL-7 treatment. This strategy also increased the half-life of bromodeoxy-uridine (BrDU) labeled memory T cells in the blood when compared to ART alone, consistent with enhanced cell survival. Further, we show that untreated SIV+ macaques have attenuated proliferation compared to uninfected macaques (and ART treated macaques) with minimally increased T cell levels following IL-7. Additionally, chronic SIV infection is associated with impaired STAT5 activation, which may possibly decrease cell survival. These data suggest that administering IL-7 at frequent intervals in conjunction with ART is the optimal strategy to obtain sustained increases of memory CD4+ T cell levels. These findings in the SIV-macaque model provide evidence that IL-7 is a potentially broad acting immune therapeutic that could be administered to HIV+ patients that do not fully restore CD4+ T cell levels after HAART treatment.Item Assessment of Gamma/Delta T Cell Functionality Following Pathogenic HIV/SIV and Non-Pathogenic SIV Infections(2007-05-22) Kosub, David Alan; Sodora, Donald L.Pathogenic HIV/SIV infection induces high viral loads, aberrant immune activation, and dysfunction in numerous immunologic cells (including gamma/delta (gamma delta ) T cells) leading to opportunistic infections. gamma delta T cells bridge the innate and adaptive immune responses primarily via cytokines produced in response to microbial phosphoantigens. gamma delta T cells have also been implicated in the control of an SIV challenge infection as evidenced by increased numbers and beta -chemokine expression at mucosal sites in vaccinated macaques. The goal of Aim 1 of this thesis was to assess the impact of an acute SIV infection on the levels of gamma delta T cells at mucosal and lymphoid sites in macaques utilizing quantitative PCR. At two days post-infection, a decrease in gamma delta T cell levels was observed at mucosa sites whereas increased levels were present at regional lymph nodes. Also, an increase in lymphoid homing molecules was observed at these lymph nodes, indicating a mechanism whereby gamma delta T cells migrate away from mucosal sites towards secondary lymphoid tissues following an acute SIV infection. The redistribution of gamma delta T cells may be important for the initiation of an anti-viral immune response and control of rapid viral spread. The goal of Aims 2 and 3 was to assess the ability of gamma delta T cells in HIV-infected patients to express cytokines and compare these results to analysis of the non-pathogenic SIV infection of sooty mangabeys. Following stimulation with the non-specific activators PMA/Ionomycin or the gamma delta TCR specific ligand isopentenyl pyrophosphate, a decrease in the percentages of gamma delta T cells expressing Th1 pro-inflammatory cytokines including TNF-alpha and IFN-gamma was observed in the HIV+ patients (regardless of CD4+ T cell levels). Highly active anti-retroviral therapy (HAART) partially restored the ability of gamma delta T cells from HIV+ patients to express Th1 cytokines. SIV infection of mangabeys results in high viral replication, low levels of immune activation, and generally no signs of progression to AIDS. Evidence for preserved or increased functionality of gamma delta T cells from SIV+ mangabeys (regardless of CD4+ T cell levels) was demonstrated by maintained percentages of gamma delta T cells that expressed Th1 cytokines following ex vivo stimulation. These data suggest that in the absence of aberrant immune activation, controlled Th1 responses by gamma delta T cells from mangabeys may assist in suppressing damage due to the SIV infection as well as inhibiting the onset of opportunistic infections. These data provide rationale for therapies aimed at increasing gamma delta T cell functionality in humans, particularly with regard to Th1 cytokine responses to augment protection against opportunistic infections and HIV disease progression.Item Depression in the HIV/AIDS Community: A Psychometric Study of the Quick Inventory of Depressive Symptomatology and Assessment of Risk Factors for Depression(2007-12-18) Merlock, Megan Christine Viola; Collins, MichelleOver the last two decades, medical advancements in the detection and treatment of Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) have allowed patients with HIV/AIDS to live longer such that the disease is now viewed as a chronic, manageable illness.research has overwhelmingly shown that depression in this population is associated with poorer course of illness and shorter lifespan. Despite such findings, few studies have addressed the utility of assessment tools which may assist clinicians in assessing depression among HIV/AIDS patients. The present study is the first to evaluate the psychometric properties of the Quick Inventory of Depressive Psychology-Self-Report (QIDS-SR) version which is a 16 - item measure of depressive severity, in HIV/AIDS patients. Three hundred and seventy one male outpatient seeking mental health treatment at a community-based HIV/AIDS clinic were recruited for the study. Patients completed the QIDS-SR and a subset also completed the Beck Depression Inventory Second Edition (BDI-II) along with a demographic questionnaire. Statistical analyses indicated that a cutoff score of 8.0 on the QIDS-SR distinguishes between depressed and not depressed patients with 95-97% sensitivity and84-88% specificity. Factor analysis revealed the QIDS-SR to be unidimensional in this sample.Total scores for the QIDS-SR showed high correlations with diagnosis of depresion by psychiatrists (.71) and total socres on the BDI-II (.90). Internal consistency was strong for the QIDS-SR (Cronbach's alpha=.85). Risk factors commonly associated with depression in the general population - unemployment and low education achieved - were not predictive of depression and the sample of male HIV/AIDS outpatients, nor were additional factors of sexual orientation and ethnic minority status. Thus, the QIDS-SR demonstarted acceptable concurrent and convergent validity and internal consistency. These strong psychometric properties along with the self-report format, brief administrations time, and unifactorial structure make the QIDS-SR a valuable clinical instrument for use in the HIV/AIDS population.Item HIV anti-retroviral trials: a paradigm for clinical research(1995-02-09) Keiser, PhilipItem HIV in the lower Rio Grande Valley(2002-10-24) Sinclair, GaryItem HIV-Associated metabolic abnormalities: prevalence, pathogenesis, cardiovascular risk and management(2006-11-17) Bedimo, RogerItem HIV-associated neurocognitive disorder(2013-01-18) Kitchell, EllenItem Lipodystrophy and metabolic syndrome in HIV-infected patients(2000-09-28) Garg, AbhimanyuItem [News](1988-11-18) Fenley, BobItem A Novel Platform to Generate Synthetic Vaccine Candidates(2012-07-10) Case, Allison Carroll; Vitetta, Ellen S.Vaccination remains the optimal means to prevent infectious disease by inducing antibodies that confer protective immunity against the pathogen in question [1-3]. However, there remain viruses against which no effective vaccines exists including human immunodeficiency virus (HIV), West Nile Virus (WNV) and hepatitis C virus (HCV). These viruses and others evade the immune response by undergoing rapid mutations in immunodominant epitopes [4-6]. In addition, although they usually express conserved epitopes that are important for inducing neutralizing antibodies, in many cases these are not immunodominant. Traditional techniques in vaccine development have not been able to overcome these barriers for these and other viruses. Subunit and peptide vaccines are very safe but it is often difficult to identify the key epitopes needed to make them effective. New approaches to developing safe vaccines that induce broadly neutralizing antibodies are needed. Therefore, the long term goal of this project was to generate vaccine candidates for any virus for which a neutralizing antibody existed or could be made without prior knowledge of the protective epitope(s). Furthermore, we desired a way to administer these vaccine candidates safely and before exposure so as to induce neutralizing antibodies. To accomplish these goals, we began with the development of a platform to generate synthetic vaccine candidates. This platform consisted of 1) libraries of B cell epitopes or “shapes” prepared by displaying peptoid sequences on beads, 2) neutralizing monoclonal antibodies (MAbs) to select the peptoids that bound to the antibody’s antigen-combining site, and 3) protein G dynabeads (PGDs) and a magnet to bind and isolate antibody bound peptoid beads. Any sequences identified in the platform as potential B cell mimetics were further evaluated in two validation assays. The first consisted of a “color screening” assay to determine that the isolated on-bead peptoids were bound by antibody. The second confirmed that these peptoids would fail to be bound by antibody if an excess of the native antigen was added (i.e. that peptoid sequences were bound by the antibody’s binding sites). The major accomplishments to emerge from this study were 1) the creation of an optimized magnetic screening platform for the isolation of peptide B cell epitopes from an on-bead library, 2) a magnetic screening platform optimized for the isolation of peptoid B cell epitopes from a peptoid library, and 3) the identification of potential peptoid B cell epitope mimetics of FLAG peptide from a peptoid library using a MAb. Taken together, a sensitive, specific, and reproducible platform to identify vaccine candidates from a peptoid library was created. This platform is particularly important for viruses like HIV, HCV, and WNV where mutation makes foreknowledge of conserved, neutralizing epitopes difficult. Once sufficiently large and diverse libraries are created, the B cell epitope mimetics (vaccine candidates) identifiable by this platform will have several advantages over their peptide counterparts. These peptoid-based vaccines are “safe” as there is no potential for reversion, they are less expensive and faster to synthesize than peptides, they are not dependent on the twenty amino acids, and the B cell epitopes identified with this platform can be conjugated to carrier in such a way that the multivalency and immunodominance can be controlled making this platform advantageous both to the generation of new vaccine candidates and in reformulating current vaccines.Item Item [Southwestern News](1997-04-28) Stieglitz, HeatherItem [Southwestern News](2000-01-24) Baxter, MindyItem [Southwestern News](1999-10-15) Steeves, Susan A.Item [Southwestern News](1999-09-14) McNeill, Bridgette RoseItem [Southwestern News](1998-05-20) Stieglitz, HeatherItem [Southwestern News](2002-07-24) Baxter, MindyItem [UT Southwestern Medical Center News](2010-09-10) Shear, Kristen HollandItem [UT Southwestern Medical Center News](2006-10-12) Rian, Russell