Browsing by Subject "HIV"
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Item African Americans and HIV/AIDS-related bereavement: an exploratory study of loss, coping, and help-seeking(2009-08) Allen, Sydnye Dyan; Hazen, HazenThe purpose of this study was to understand how individuals from African American families process the HIV/AIDS-related bereavement of a loved one. A sample of African American adults age 18 and older who experienced the loss of a loved one to HIV/AIDS-related death were interviewed for this study. Qualitative methodology was employed for data collection and thematic analysis was used to identify central themes. Due to the exploratory nature of the study, emergent themes regarding AIDS related bereavement were expected. It was postulated that African American individuals shared experiences related to HIV/AIDS-related loss. Individuals were also expected to report unique bereavement experiences. In particular, prolonged grief and internalized coping strategies were expected to impact bereavement experiences of individuals in families acutely affected by HIV/AIDS-related stigmatization. Secrecy about a loved one’s HIV/AIDS-related death was expected to impact the ability of bereaved persons to process and effectively cope with loss; results yielded evidence of protracted states of shame or blame regarding loss. The findings of this study are useful for identifying methods for targeting bereavement resources toward individuals who are underrepresented in HIV/AIDS-related intervention programs.Item Analyses of infectious disease data with attention to heterogeneity(2013-08) O'Dea, Eamon Brendin; Wilke, C. (Claus); Meyers, Lauren AncelThis work comprises three projects that extend previous models to include features of practical significance for the statistical analysis of infectious disease data. In the first, we find from a simulation study how the degree of heterogeneity in the number contacts that individuals have affects the relationship between estimates of a pathogen's effective population size based on coalescent theory and the true prevalence and incidence of that pathogen. In the second, we find that aggregating data from many small outbreaks allows the parameters of stochastic epidemic models to be consistently estimated with a generalized linear model. Application of this method to a set of 77 small norovirus outbreaks reveals interesting differences in the transmission parameters between hospital and nursing-home outbreaks. In the third project, we gain insight into HIV contact networks in the United States by fitting data from a number of surveys to a simple stochastic model of a dynamic network.Item The application of aptamer microarraying techniques to the detection of HIV-1 reverse transcriptase and its mutant variants(2010-08) Syrett, Heather Angel; Ellington, Andrew D.; Kitto, George B.; Willets, Katherine A.; Iyer, Vishwanath R.; Yin, Yuhui W.The work described here details the experimental progress toward an improved means of HIV-1 diagnosis and an explanation of the experimental approaches taken to advance a previously developed HIV-1 reverse transcriptase detection assay using RNA aptamers for protein capture. After characterization of the identity and function of the aptamer samples to be used, we first set about clarifying the nature of the assay and pinning down sources of variability inherent in the original Aptamer Antibody Sandwich Assay (AASA) such that through the course of this work we might bring the assay to a point of high reproducibility. In doing so, we devised a set of criteria for data analysis and filtration and established a process to examine whether modifications to the method resulted in measurable improvement. Two new methods were tested in the hope that they might later be extended to our ultimate project goal of distinguishing binding affinity variations among HIV-1 reverse transcriptase protein and its mutant variants. Both method modifications involved the addition of a fluorescently labeled Cy5 probe to the immobilized aptamer construct. The addition of a fluorescent label to each printed aptamer allowed for detection of aptamer presence in addition to protein binding, essentially serving as a simple internal control for aptamer-protein binding. After optimizing the AASA aptamer construct and experimental procedure, the AASA was extended to a multiplexed array format. Using four groups of aptamers selected against two HIV-1 RT variants (wild-type and mutant 3) we tested the hypothesis that immobilized anti-HIV-1 aptamers might be capable of binding HIV-1 RT variants and regardless of their selective target. The experiments described here are the first example of these aptamers being used in a multiplexed array format, and the results are not only a clear exemplification of the capacity of RNA aptamers for detection in this novel, immobilized assay format, but also an indicator of the utility and flexibility of RNA aptamer functionality. The promising results described in these preliminary studies are the starting block from which several interesting aptamer-protein interaction and drug-competition studies have begun.Item Assessing the Efficacy of Interleukin-7 as an Immunotherapeutic in the SIV+ Rhesus Macaque Model(2010-01-12T18:54:52Z) 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. [Keywords: HIV/AIDS; SIV; immunotherapy; Interleukin-7 (IL-7); Rhesus Macaque]Item Assessment of CD4+ T Cell Depletion And Monocyte Function During Nonpathogenic SIV Infection of Sooty Mangabeys(2011-02-01T19:36:48Z) Mir, Kiran D.; Sodora, DonaldSIV-infected sooty mangabeys maintain low levels of chronic immune activation and do not progress to AIDS, making them an important model for elucidating the mechanisms contributing to AIDS pathogenesis. The studies presented here utilize the mangabey model of nonpathogenic SIV infection to assess the impact of CD4+ T cell depletion on immune activation in SIV-infected mangabeys and to assess the contribution of monocytes to nonpathogenic SIV infection. The Sodora laboratory previously identified a cohort of SIV-infected sooty mangabeys that experienced a virally-mediated severe decline in CD4+ T cells yet did not develop opportunistic infections or AIDS. Here, we assessed the immune competence of three mangabeys following viral passage from one CD4-low mangabey that resulted in a dramatic decline in CD4+ T cells within 21 days-post-infection. Despite the rapid depletion of CD4+ T cells, all mangabeys maintained low levels of chronic immune activation and mounted adaptive immune responses to SIV and influenza vaccination. To investigate the contribution of monocytes to the low levels of immune activation, we assessed the effector function of monocytes in SIV-infected CD4-low and CD4-healthy sooty mangabeys. We found that, compared to SIV-negative mangabeys, monocytes from SIV-infected mangabeys produced significantly less TNF-alpha upon stimulation with lipopolysaccharide (LPS). In contrast, hosts of a pathogenic infection, including SIV-infected macaques and HIV-infected humans, displayed no change in monocyte TNF-alpha responses relative to uninfected controls. In mangabey PBMC cultures, stimulation with LPS led to increases in CD8+ T cell activation that could be inhibited in a dose-dependent manner by TNF-alpha –blocking antibodies. Taken together, these results suggest that TNF-alpha production from monocytes can contribute to increases in immune activation and that SIV-infected sooty mangabeys regulate the monocyte response to LPS as one means to avoid chronic immune activation during SIV infection. These studies expand the current knowledge of the mechanisms by which SIV-infected natural hosts avoid progression to AIDS and underscore the importance of controlling immune activation during lentiviral infection, which may inform the next generation of therapies and vaccines for HIV patients.Item Assessment of Gamma/Delta T Cell Functionality Following Pathogenic HIV/SIV and Non-Pathogenic SIV Infections(2007-05-22) Kosub, David Alan; Sodora, DonaldPathogenic 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 An assessment of kilocalories and protein in the diets of HIV-infected adults in Kenya(2011-05-15) Elizabeth Mary Vaughan; Victor Cardenas, MD; Harvey Bunce, PhD; Christine Arcari, PhDINTRODUCTION: The detrimental effects of HIV are well known throughout the world. This public health burden is particularly evident in Kenya, Africa, where 6.7% of adults are infected with HIV. One problem of those living with HIV in this resource-poor country is the concurrent existence of malnutrition. Previous investigators undertook many studies to bridge the link between HIV and malnutrition. However, they were unable to gather individual diet information to allow accurate estimation of kilocalorie and protein needs. These deficits hinder accurate dietary interventions for these patients. \r\nMETHODS: Over the period of April 2009 to August 2009, we designed and implemented a dietary instrument (3-day recall survey) to assess the kilocalorie and protein consumption for HIV-infected adults in Kijabe, Kenya. We used this data to compare subject consumption to predicted nutrient needs. We used Harris-Benedict (HB) and Mifflin formulas for kilocalorie need predictions and World Health Organization (WHO) equation for protein need predictions. We then characterized the relationship between dietary intake, BMI and CD4 levels.\r\nRESULTS: A total of 201 patients were surveyed, 122 (60.7% [27% males, 73% females]) met inclusion criteria. There was no statistical difference between HB and Mifflin equations for kilocalories. Males averaged 68.8% (SD 23.3) of estimated kilocalorie requirements (HB) and 100.5% (SD 45.3) of protein. Women averaged 74.4% (SD 24.4) of kilocalorie needs (HB) and 100.5% (SD 42.5) of protein. Differences between genders were not statistically significant (p=0.247 [kilocalorie], p=0.936 [protein]). There was a significant correlation between protein intake and CD4 for males (r=0.7035, p=0.0004) but not for females (r=-0.1911, p=0.1546). There was no statistical significance found between kilocalories (male r=0.104, p=0.654; female r=0.0420, p=0.765) and CD4. No relationship was found between nutrient intake and BMI (male p=0.690; female p=0.477).\r\nCONCLUSIONS: A 3-day recall dietary assessment appears to be an adequate method to obtain dietary information for adult HIV patients in East Africa. Further, we conclude that current predictive formulas for protein underestimate needs in the male HIV population. \r\nItem Brazil's HIV/ AIDS model : Is it working Fortaleza? - Spatial analysis of HIV/ AIDS(2012-05) Ponte, Renata Cidrão; Miller, Jennifer A. (Jennifer Anne); Batnitzky, AdinaThe prevalence rate of the Human Immunodeficiency Virus (HIV) in Brazil has stabilized since the year 2000 at approximately 0.35 percent of the total population (600,000 people). Most researchers and political actors agree that the success in HIV management has been highly correlated with some of the policies that the Brazilian government has implemented concerning the HIV/ AIDS positive population (Levi et al 2002; Dourado 2006; Parker 2009). With worldwide recognition of this accomplishment, one must wonder why it is that the North and Northeast regions of Brazil have been experiencing trends of increasing HIV/ AIDS incidence in the past decade (Nunn et al 2009). This study concentrates on the spatial distribution of HIV incidence in the year 2000, as it uncovers how HIV distribution can be related to aspects of marginalization in the second-most populous Northeastern municipality; Fortaleza, Brazil. The central hypothesis of this research states that HIV incidence is positively correlated with rate of marginalization. Marginalization is considered as the sector of population without access to basic social services, such as education, running water, and appropriate housing. Spatial patterns of HIV and marginalization are examined and interpreted in the context of the Brazilian Model. This research suggests that although marginalization has a strong spatial pattern, HIV is not demographically or geographically discriminatory.Item Characterization of HIV-1 Reverse Transcriptase substrate specificity by conformationally sensitive fluorescence(2010-12) Kellinger, Matthew William; Johnson, Kenneth Allen; Dalby, Kevin; Robertus, Jon; Russell, Rick; Zhang, Yan JessieWe have engineered a mutant of HIV Reverse Transcriptase that can be fluorescently labeled by covalent attachment of the environmentally sensitive fluorophore 7-diethylamino-3-((((2-maleimidyl)ethyl)amino)carbonyl)coumarin (MDCC). The result is a polymerase that is kinetically indistinguishable from the wild-type enzyme, but provides a signal to monitor changes in enzyme structure that result from conformational changes induced by substrate binding. Using this system, we have expanded the kinetic model governing nucleotide binding to include an enzymatic isomerization following initial nucleotide binding. In doing so, we define the role of induced-fit in nucleotide specificity and mismatch discrimination. Additionally, we have characterized the kinetics governing the specificity and discrimination of several widely administered Nucleotide Reverse Transcriptase Inhibitors (NRTI’s) used to combat HIV infection including 3TC (Lamivudine), FTC (Emtricitabine), and AZT (Zidovudine) for the wild-type polymerase and mutants with clinical resistance to these compounds. Our findings resolve the apparent tighter binding of these inhibitor compounds compared to the correct nucleotide by showing that the affinity for the correct nucleotide is stronger than the inhibitors. The apparent weaker binding of the correct nucleotide is a result of a incomplete interpretation of binding data that fails to account for the importance of the reverse rate of the conformational change. The apparent Kd (Kd,app) measurements for correct nucleotide estimates Km rather than Kd because nucleotide binding does not reach equilibrium. The conformationally sensitive enzyme has also been used to characterize the kinetics governing DNA association. We show that DNA binding is governed by a two-step process where a fast initial association is followed by a second, slow isomerization that is off the pathway for nucleotide binding and incorporation. Finally, we have implemented single molecule techniques using fluorophore labeled nucleotides to study the effects of AZT incorporation on the DNA translocation dynamics of the polymerase. We find that primer termination with AZT results in DNA that fails to translocate, therefore occluding the next nucleotide from binding. This shift in translocation equilibrium exposes the newly formed phosphodiester bond to ATP- or pyrophosphate-mediated AZT excision; thereby rescuing productive polymerization. This finding represents the first kinetic measurement of DNA translocation by a polymerase.Item Characterization of Viral Entry Inhibitors(2014-08-06) Chamoun Emanuelli, Ana MHepatitis C virus (HCV), Human Immunodeficiency virus (HIV) and Herpes Simplex virus (HSV) are pathogenic viruses known to cause liver disorder, acquired immunodeficiency and skin lesions, respectively. Although current therapies have played substantial roles in the fight against these pathogens, their use is limited and for the most part does not result in viral eradication. Moreover, most antivirals target viral encoded structures which overtime foster the development of resistant strains. Hence, antivirals aimed at preventing initial infection represent a promising strategy for viral combat. This dissertation focuses on the characterization of viral entry inhibitors and their potential use. The first compounds evaluated come from the phenothiazines family, widely used as antipsychotic drugs. Phenothiazines were shown to suppress HCV entry by intercalating into cholesterol-rich membrane domains of target cells thus reducing viral-host fusion. The second candidates studied are two members of the H1-anthistamines currently used for allergy treatment. Both compounds strongly reduce HCV entry, likely at the fusion step, and its inhibition was associated with cholesterol content in the virion and host cells, pointing to the use of an NPC1L1-receptor dependent mechanism. Lastly, we evaluated the antiviral activity of PD 404,182 (PD) as an alternate treatment for HCV-HIV coinfected patients as well as its potential use as an anti-HIV microbicide. PD is able to reduce viral entry of the three pathogens through physical disruption of virions releasing the nucleic acids into the surrounding medium. Moreover, PD possesses several qualities pointing to its use as a potential microbicide.Item Conformational dynamics plays a significant role in HIV reverse transcriptase resistance and substrate selection(2012-12) Nguyen, Virginia Myanh; Johnson, Kenneth AllenHuman immunodeficiency virus reverse transcriptase (HIV RT) is a virally encoded polymerase responsible for replicating the HIV genome. Most HIV treatments include nucleotide RT inhibitors (NRTIs) which inhibit HIV RT replication by serving as a substrate for the polymerase reaction but then blocks subsequent polymerization after incorporation. However, resistance to these NRTIs may occur through specific mutations in HIV RT that increase the discrimination of HIV RT for natural nucleotides over NRTIs. The role of enzyme conformational dynamics in specificity and substrate selection was studied using transient kinetic methods on HIV RT enzymes that have been site-specifically labeled with a conformationally sensitive fluorophore, to measure the rates of binding and catalysis. First, HIV RT with the mutation of lysine to arginine at the residue position 65 (K65R) was examined for its resistance against the NRTI tenofovir diphosphate (TFV), an acyclic deoxyadenosine triphosphate (dATP) analog. It was found that HIV RT K65R resistance to TFV was achieved through decreased rates of catalysis and increased rates of dissociation for TFV over dATP when compared with the kinetics of wild-type HIV RT. Moreover, global fitting analysis confirmed a mechanism where a large conformational change, after initial ground state binding of the substrate, contributed significantly to enzyme specificity. This led to our investigation of the molecular basis for enzyme specificity using HIV RT as a model system. Again, transient kinetic methods were applied with the addition of molecular dynamics simulations. The simulated results were substantiated by the corroborating experimental results. It was found that a substrate-induced conformational change in the transition of HIV RT from an open nucleotide-bound state to a closed nucleotide-bound state was the major determinant in enzyme specificity. The molecular basis for substrate selection resulted from the molecular alignments of the substrate in the active-site, which induced the conformational change. When the correct nucleotide was bound, optimal molecular interactions in the active-site yielded a stably closed complex, which promoted nucleotide incorporation. In contrast, when an incorrect nucleotide was bound, the molecular interactions at the active-site were not ideal, which yielded an unstable closed complex, which promoted substrate dissociation rather than incorporation.Item Constructing spirit-level interventions for African American women living with HIV(2012-05) Runnels, Ratonia Cheryl; Pomeroy, Elizabeth Cheney, 1955-African Americans are disproportionately affected by HIV comprising only 12% of the U.S. population but accounting for nearly 50% of all HIV cases (CDC, 2009). HIV surveillance data estimate that one in 30 Black women will be diagnosed with HIV during their lifetime. For many HIV positive African American women, treatment of HIV infection and the subsequent psychological stress is complicated by lack of resources and competing life priorities. These women also face additional challenges such as fear of disclosure and lack of adequate social support. The complexity of challenges faced by African American women who are HIV positive highlight the need to explore their preferred ways of coping. Studies show that minority women tend to utilize alternative coping strategies when faced with dual mental and physical health challenges. Spirituality has been found to have a direct relationship with cognitive and social functioning and inversely related to HIV symptoms among African American women. Psychosocial interventions are a key component to improved quality of life for women living with HIV and spirit-level interventions are shown to buffer psychosocial distress experienced by HIV positive persons. This dissertation will consist of three publishable quality articles that examine issues associated with the function of spirituality in HIV positive women. This first article will review published spiritually oriented interventions and compare, contrast, and critique the various components, sample, and intervention methods to determine the applicability and replicability of these interventions as a basis for increasing treatment options for co-morbid African American women. The second article will offer a conceptual framework incorporating the health belief model and a discussion of Lazarus & Folkman's stress and coping model to examine theoretical frameworks for integrating spirituality into social work practice interventions for HIV positive women. The third article for this dissertation seeks to contribute new information to the literature on the spirituality in the lives of HIV positive women. This article will present data that identifies, defines, and describes various uses of spirituality as a coping mechanism. The article will also discuss historical factors that influence the use of religion and spirituality among African Americans.Item Coping strategies among Mexican American women living with HIV(2010-12) Rodríguez-Escobar, Yolanda 1954-; Pomeroy, Elizabeth Cheney, 1955-The literature has documented the disproportionate rate of HIV infection among women of color, mainly, African American women and Latinas. The current trend shows that the number of cases affecting these sub-populations will continue to increase. A gap exists in the literature in understanding the coping strategies of Mexican American women living with HIV. Using an ethnographic approach, this research answers the central question of how Mexican American women live with and make meaning of their HIV status. This researcher used a sample of 15 Mexican American women living with HIV who had participated in the Mujeres Unidas support group in San Antonio, Texas. The most common theme found was how the role of faith was central to their lives. It was clear that this belief served as their primary source of strength. The findings suggest the need for social workers to examine new paradigms, strategies, and interventions that focus on the broad social, economic, and community factors that put Mexican American women disproportionately at risk for HIV. These factors include poverty, income and wealth inequality, poor quality of life, racism, sexism, and low socioeconomic status, which are all major risk factors for ill health and health disparities. This research demands that social workers and other researchers examining coping skills address the issues of resiliency and strengths perspective in understanding the ways in which the life journey unfolds for Mexican American women living with HIV. Although, this study focused on Mexican American women, future research is needed to compare this group to other women living with HIV as there may be cultural differences that exist. Additional research is needed in studying the role that religion plays in the lives of Mexican American women living with HIV as many of the participants revealed that they left things up to “God’s will.” Among the unexpected findings, the theme of viewing their situation from the perspective of “Un dia a la vez” (One day at a time) suggests that the belief that the course of their lives is not necessarily under their control which could be related to fatalism (fatalism).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 “The gay Facebook” : friendship, desirability, and HIV in the lives of the gay Internet generation(2013-12) Robinson, Brandon Andrew; González-López, Gloria, 1960-Why are men seeking other men online? And how does the Internet influence these men and their sexuality? These are the two underlying questions driving this thesis. To answer these general questions, I conducted a qualitative study, which used in-depth individual interviews with 15 men who have sex with other men who self-identified as gay, queer, or homosexual. Through employing a theoretical framework that is inspired in queer theory, I uncovered three main topics in these men’s lives that are intimately shaped by their use of the Internet: friendship, racial and bodily desire, and HIV. First, I show the creative ways gay men are using the Internet, and specifically a sexualized space, in order to build relations with other gay men, despite the larger obstacles a heteronormative society puts in these men’s way to forge these friendships. In using their gay identity to try to establish relationalities with other gay identified men, the informants in this study challenge the impersonable traits associated with modernity, while seeking to build new alliances that could potentially radically disrupt heteronormative society. Secondly, I highlight how the social exclusionary practices toward people of color and non-normal bodies on Adam4Adam.com reifies whiteness and masculinity, which in turn, reifies heteronormativity. Here, I unmask how the structure of Adam4Adam.com, especially its filtering system, normalizes these discriminatory practices in users’ lives. Thirdly, I examine the role and meaning of HIV and sexual health in the lives of my informants. I incorporate the term “doing sexual responsibility” to show how my gay informants manage their anxiety-ridden lives when navigating their sexuality and sexual health. I also show how the gay men in this study engage in online foreplay as a pleasurable way to manage this anxiety and how trust and hegemonic masculinity are unintended consequences of this danger discourse on sexuality. As these men’s narratives and this thesis illustrate, society is still structured through heteronormative standards, but the Internet provides a new space for gay men to navigate their marginalized status in society.Item HIV and AIDS in the Russian Federation : prisons as a case study of risk environments and agency(2011-05) Severson, Jamie LeeAnn; Buckley, Cynthia J.; Angel, Jacqueline LThis thesis explores Russian prisons as risk environments for the spread of HIV through intravenous drug use. The Russian HIV epidemic is extremely fast growing, and though exact prevalence rates are unknown, the epidemic is now considered generalized as estimated prevalence rates exceed one percent of the Russian population. After decades of foreign-aid and interventions in African nations have largely failed to address the HIV epidemic, social scientists now attribute HIV infection to risk environments created by low levels of social cohesion and a lack of agency. Within my research, I explore Russian male prisons and the role risk environments and agency play in the spread of HIV. I review recently published literature, government statistics, as well as reports published by non-governmental organizations. I then analyze and interpret these data, draw conclusions and inferences regarding the spread of HIV within Russian prison risk environments.Item Improving secondary structure prediction with covariation analysis and structure-based alignment system of RNA sequences(2013-12) Shang, Lei, active 2013; Gutell, RobinRNA molecules form complex higher-order structures which are essential to perform their biological activities. The accurate prediction of an RNA secondary structure and other higher-order structural constraints will significantly enhance the understanding of RNA molecules and help interpret their functions. Covariation analysis is the predominant computational method to accurately predict the base pairs in the secondary structure of RNAs. I developed a novel and powerful covariation method, Phylogenetic Events Count (PEC) method, to determine the positional covariation. The application of the PEC method onto a bacterial 16S rRNA sequence alignment proves that it is more sensitive and accurate than other mutual information based method in the identification of base-pairs and other structural constraints of the RNA structure. The analysis also discoveries a new type of structural constraint – neighbor effect, between sets of nucleotides that are in proximity in the three dimensional RNA structure with weaker but significant covariation with one another. Utilizing these covariation methods, a proposed secondary structure model of an entire HIV-1 genome RNA is evaluated. The results reveal that vast majority of the predicted base pairs in the proposed HIV-1 secondary structure model do not have covariation, thus lack the support from comparative analysis. Generating the most accurate multiple sequence alignment is fundamental and essential of performing high-quality comparative analysis. The rapid determination of nucleic acid sequences dramatically increases the number of available sequences. Thus developing the accurate and rapid alignment program for these RNA sequences has become a vital and challenging task to decipher the maximum amount of information from the data. A template-based RNA sequence alignment system, CRWAlign-2, is developed to accurately align new sequences to an existing reference sequence alignment based on primary and secondary structural similarity. A comparison of CRWAlign-2 with eight alternative widely-used alignment programs reveals that CRWAlign-2 outperforms other programs in aligning new sequences with higher accuracy. In addition to aligning sequences accurately, CRWAlign-2 also creates secondary structure models for each sequence to be aligned, which provides very useful information for the comparative analysis of RNA sequences and structures. The CRWAlign-2 program also provides opportunities for multiple areas including the identification of chimeric 16S rRNA sequences generated in microbiome sequencing projects.Item 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. [Keywords: vaccine, novel, peptoid(s), mimetic(s), human immunodeficiency virus (HIV), platform, B cell epitopes, peptide]Item Persistent “hijacking” of brain proteasomes in HIV-associated dementia(2008-11-05) Trung Phuoc Nguyen; Benjamin B. Gelman, MD, PhD; Miles W. Cloyd, PhD; Dennis L. Kolson, MD, PhD; David J. McAdoo, PhD; Claudio A. Soto, PhDHuman immunodeficiency virus-1 (HIV) infection of the central nervous system results in a syndrome of neuropsychological impairment, motor deficits, and behavioral changes diagnosed as HIV-associated dementia. Findings of increased ubiquitin-stained deposits and high molecular weight ubiquitin-protein conjugates in brains of HIV-positive subjects suggest impaired protein turnover by the ubiquitin-proteasome system analogous to neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. HIV infection of the brain and the consequent inflammatory response was hypothesized to alter the ubiquitin-proteasome system, leading to altered brain protein turnover and neuronal function. Investigations into the ubiquitin-proteasome system in HIV-infected brains were performed using the resources of the Texas NeuroAIDS Research Center and the National NeuroAIDS Tissue Consortium, including clinical data and frontal cortex brain tissue from 153 autopsy cases. Assessment of frontal cortex proteasome proteolytic activity revealed an abnormal catalytic profile that was more severe in those with HIV-associated neuropsychological impairment or HIV encephalitis. Proteasome subunit composition analysis by immunoblotting showed increases in immunoproteasome subunits LMP7 and PA28 alpha and decreases in constitutive proteasome regulatory subunit Rpn2 in the frontal cortex of HIV-positive subjects that correlated with the abnormal proteasome proteinase profile and were associated with neuropsychological impairment and HIV encephalitis. Immunoproteasome increases correlated with lower performance on neurocognitive tests specific for frontal lobe functioning domains, providing indications of regional specificity. Immunoproteasome increases also correlated with increases in frontal cortex tissue HIV loads. Immunoproteasomes were localized by immunofluorescence to the perikarya and distal processes of neurons, as well as to oligodendrocytes, astrocytes, and microglia. The potential consequence of immunoproteasomes in neurons was investigated with the analysis of synaptic proteins. Decreases in synaptophysin correlated with immunoproteasome increases, indicating the potential for synaptic protein alterations associated with immunoproteasomes. Analysis of isolated nerve endings, or synaptosomes, revealed immunoproteasome increases in synapses of HIV-positive subjects that correlated with increases in 14-3-3 zeta and decreases in synapsin 1. These findings suggest “hijacking” of constitutive proteasomes by immunoproteasomes with the persistent inflammatory response in HIV-infected brains. Ubiquitin-mediated protein turnover by constitutive proteasomes is consequently impaired, resulting in the dysregulation of neuronal and synaptic protein composition that leads to neuronal dysfunction.Item A retrospective evaluation of the relationship between mental disorders and patient adherence to antiretroviral therapy(2009-12) Fowler, Jill Aglaia; Crismon, M. Lynn; Barner, Jamie C.; Argo, Tami R.; Smith, Tawny B.Adherence to combination antiretroviral therapy is important for achieving optimal HIV-related outcomes. Epidemiologic data indicate that persons with mental disorders are disproportionately affected by HIV/AIDS, which is concerning since having a mental disorder has been associated with poor adherence to medications for treatment of chronic disease states. The purpose of this study was to examine the relationship between the presence of mental disorders and adherence to combination antiretroviral therapy. Additionally, this study examined the relationship between adherence to psychotropic medications and adherence to antiretroviral therapy. Study data were collected from the Texas Medicaid Vendor Drug Program database and Texas Medicaid enrollment files. Adherence to and persistence with antiretroviral therapy, as well as adherence to psychotropic medications when applicable, were evaluated over a 12-month period in 1,321 patients starting a new combination antiretroviral regimen. The presence of a mental disorder was defined based on prescription claims for psychotropic medications. Proportion of days covered was used to calculate adherence, while persistence was defined as the number of days persistent with all antiretrovirals in the index regimen. Logistic regression was used to evaluate the relationship between psychotropic medication use and adherence to antiretroviral therapy (90% cut-off), as well as the relationship between adherence to psychotropic medications (80% cut-off) and adherence to antiretroviral therapy. The relationship between antiretroviral persistence and psychotropic medication use was evaluated using multiple linear regression. Factorial ANOVA was used to evaluate the interactions between race/ethnicity, gender, and psychotropic medication use in their effects on adherence to and persistence with antiretroviral therapy. No significant relationship was found between the presence of a mental disorder and adherence to or persistence with combination antiretroviral therapy in this study. However, the limitations of using psychotropic medication use as a proxy for mental disorders may have affected the results. Adherence to psychotropic medications overall (n = 501; OR = 3.37, 95% CI: 1.86 – 6.10; p < 0.001) and specifically to antidepressants (n = 443; OR = 4.23, 95% CI: 2.31 – 7.75; p < 0.001) was significantly associated with adherence to antiretroviral therapy, indicating a possible relationship between effective treatment for mental disorders and combination antiretroviral therapy adherence. While additional research is needed to clarify this relationship, these data support the need for an integrated approach to treatment of mental disorders and HIV/AIDS.