Medicine and Health Sciences Commons^™

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) Infection By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4⁺ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Evaluating Racial And Ethnic Disparities In Access To Primary Care Among Gay And Bisexual Men In The Us, A Population At High-Risk Of Hiv Infection, Jessica S. Kiernan, April D. Kimmel

Graduate Research Posters

BACKGROUND: 69% of new HIV diagnoses in the US are among gay and bisexual men, with disparities by race and ethnicity. Primary care providers increasingly provide HIV prevention. Racial and ethnic disparities in primary care access are well-documented, but their persistence among gay and bisexual men is unknown. We examined racial and ethnic disparities in access to primary care among this population.

METHODS: We used nationally representative person-level sociodemographic, health status and utilization data, and data on organizational- and socially determinant barriers to care, from the National Health Interview Survey, 2013-2018. Outcomes were: 1) general physician visit

RESULTS: The sample …

Developing An Evidence-Based Hiv Testing Message For Young African American Women, Melanie P. Moore

Theses and Dissertations

African American women have the highest rates of HIV infection among women of all racial/ethnic groups in the United States, and over 50% of HIV infected young adults are unaware of their infection. HIV testing is a cost-effective mechanism for reducing HIV transmission. Despite this, limited research has been devoted to developing interventions specifically promoting HIV testing. This two-part study proposed to address this gap through developing a culturally tailored HIV testing message aimed at increasing HIV test intentions among young African American women. Study 1 was a quantitative study that examined predictors of HIV testing history and future HIV …

Cellular Mechanisms By Which Alcohol Promotes Hiv Protease Inhibitor-Induced Hepatotoxicity, Michael Hinton

Theses and Dissertations

CELLULAR MECHANISMS BY WHICH ALCOHOL PROMOTES HIV PROTEASE INHIBITOR-INDUCED HEPATOTOXICITY

Michael Hinton, B.S.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University

Virginia Commonwealth University, 2019

Major Director: Huiping Zhou

Professor, Department of Microbiology and Immunology

The development of highly-active-antiretroviral therapy(HAART) has allowed management of HIV and extended the lives of those infected. Alcohol abuse, which is very common in HIV-1 infected patients, is one of the most important co-morbid risk factors for liver injury and has been associated with the occurrence of serious metabolic syndrome and subsequent discontinuation …

How Can The Humanities Treat Hiv/Aids? An Interview With Dale Smith, Amita Rao, Emily Furlich, Dale Smith

Auctus: The Journal of Undergraduate Research and Creative Scholarship

No abstract provided.

Researching The History Of Hiv/Aids: An Interview With Christopher Ewing, Emily Furlich

Auctus: The Journal of Undergraduate Research and Creative Scholarship

No abstract provided.

On Lgbt Studies At Vcu: An Interview With Richard Godbeer, Amita Rao, Emily Furlich

Auctus: The Journal of Undergraduate Research and Creative Scholarship

No abstract provided.

Hiv Induces Expression Of Complement Component C3 In Astrocytes By Nf-Κb-Dependent Activation Of Interleukin-6 Synthesis, Jadwiga Nitkiewicz, Alejandra Borjabad, Susan Morgello, Jacinta Murray, Wei Chao, Luni Emdad, Paul B. Fisher, Mary Jane Potash, David J. Volsky

Pathology Publications

Background

Abnormal activation of the complement system contributes to some central nervous system diseases but the role of complement in HIV-associated neurocognitive disorder (HAND) is unclear.

Methods

We used real-time PCR and immunohistochemistry to detect complement expression in postmortem brain tissue from HAND patients and controls. To further investigate the basis for viral induction of gene expression in the brain, we studied the effect of HIV on C3 expression by astrocytes, innate immune effector cells, and targets of HIV. Human fetal astrocytes (HFA) were infected with HIV in culture and cellular pathways and factors involved in signaling to C3 expression …

Sex Differences In Hiv Effects On Visual Memory Among Substance-Dependent Individuals, Michael K. Keutmann, Raul Gonzalez, Pauline M. Maki, Leah H. Rubin, Jasmin Vassileva, Eileen M. Martin

Psychiatry Publications

HIV’s effects on episodic memory have not been compared systematically between male and female substance-dependent individuals. We administered the Brief Visuospatial Memory Test–Revised (BVMT–R) to 280 substance-dependent HIV+ and HIV– men and women. Groups were comparable on demographic, substance use, and comorbid characteristics. There were no significant main effects of sex or HIV serostatus on BVMT–R performance, but HIV+ women performed significantly more poorly on delayed recall. This effect was most prominent among cocaine-dependent HIV+ women. Our findings are consistent with recent speculation that memory impairment may be more common among HIV+ women, particularly those with a history of cocaine …

Effects Of Hiv And Drugs Of Abuse On The Blood-Brain Barrier, Gopika Hari

Undergraduate Research Posters

Despite effective systemic therapy, HIV-1 infection within the brain results in neuronal degradation and neurocognitive dysfunction. This neurocognitive dysfunction is worsened in the setting of opiate abuse. The central nervous system (CNS) is protected by the blood-brain barrier (BBB), a selective barrier regulating the passage of substances from peripheral circulation into the CNS. The BBB is composed of microvascular endothelial cells encased by basal lamina, pericytes, and perivascular astrocyte endfeet. Intracellular junctional complexes comprising of adherens and tight junctions are located between the endothelial cells and form tight barrier, preventing traffic of compounds between cells (paracellular flux). Clinical and in …

Enhancement Of The Placental Transmission Of Lopinavir Using A Transporter Targeted Prodrug Strategy, Meng Wang

Theses and Dissertations

Lopinavir (LPV) is a potent protease inhibitor specific for HIV-1. However, LPV has poor placental penetration due to substrate activity for efflux transporter by P-glycoprotein (P-gp). Since fatty acid transporters are highly expressed in the placenta during pregnancy, we designed fatty acid ester prodrug of lopinavir as substrates of fatty acid transporter in order to improve their uptake into placenta. Seven dicarboxylic acid esters of lopinavir have been made in our lab. The structures were characterized by ¹H-NMR, ¹³C-NMR, LC-MS/MS, HRMS, IR and melting points. After making the prodrugs, an LC-MS/MS method with high specificity and sensitivity, as …

The Role Of P2x Receptors In Hiv And Opiate-Related Neurotoxicity, Mary Sorrell

Theses and Dissertations

Emerging evidence suggests that opioid drugs can exacerbate neuroAIDS. Microglia are the principal neuroimmune effectors thought to be responsible for neuron damage in HIV-infected individuals, and evidence suggests that drugs acting via opioid receptors in microglia aggravate the neuropathophysiological effects of HIV. The P2X family of ATP activated ligand-gated ion channels regulates key aspects of microglial function. In addition, opioid-dependent microglial activation has been reported to be mediated through P2X4 signaling, prompting us to investigate P2X receptors contribution to the neurotoxic effects of HIV and morphine. In vitro experiments showed treatment with TNP-ATP prevented the neurotoxic effects of morphine and/or …

Hiv And Opiates-Mediated Neurotoxicity: Gsk3Β Is A Potential Therapeutic Target, Ruturaj Masvekar

Theses and Dissertations

HIV-1 enters the CNS soon after initial systemic infection. HIV-1 can induce a wide range of neurological deficits, collectively known as HIV-1-associated neurocognitive disorders (HAND). Mature neurons are not infected by HIV-1; instead, infected and/or activated glial cells release various viral and cellular factors that induce direct and/or indirect neuronal toxicity, leading to HAND. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes …

Development Of Antagonists Targeting Chemokine Receptor Ccr5 And The Chemokine Receptor Ccr5 – Mu Opioid Receptor Heterodimer, Christopher Kent Arnatt

Theses and Dissertations

The chemokine receptor CCR5 (CCR5) plays an integral role within the inflammatory network of cells. Importantly, CCR5 is a mediator in several disease states and can be targeted using small molecule antagonists. Within this work, CCR5’s role in prostate cancer and HIV/AIDS has been exploited in order to develop potential therapeutics and probes. First, a series of novel compounds was designed by using pharmacophore-based drug design based upon known CCR5 antagonists and molecular modeling studies of the CCR5 receptor’s three-dimensional conformation. Once synthesized, these compounds were tested for their CCR5 antagonism and their anti-proliferative effects in several prostate cancer cell …

Microglial Activation Decreases Retention Of The Protease Inhibitor Saquinavir: Implications For Hiv Treatment, Shannon Dallas, Michelle L. Block, Deborah M. Thompson, Marcelo G. Bonini, Patrick T. Ronaldson, Reina Bendayan, David S. Miller

Anatomy and Neurobiology Publications

Background

Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide.

Methods

To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent …

Patient- And Population-Level Health Consequences Of Discontinuing Antiretroviral Therapy In Settings With Inadequate Hiv Treatment Availability, April D. Kimmel, Stephen C. Resch, Xavier Anglaret, Norman Daniels, Sue J. Goldie, Christine Daniel, Angela Y. Wong, Kenneth A. Freedberg, Milton C. Weinstein

Health Behavior and Policy Publications

Background

In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes.

Methods

In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the …

Living With Hiv: Views Through The Blog, Linda Eastham

Theses and Dissertations

The purpose of this qualitative descriptive study was to develop a greater clarity of how HIV infected individuals live and work within the sphere of HIV infection as represented through unsolicited, personal narratives posted on blogs. Existing, single author, personal blogs were identified via a search engine. Blogs were defined as the blog author's postings and all responses, whether written by the blog author or a reader respondent. Inclusion and exclusion criteria were developed to respect indicators of bloggers' intentions for privacy, e.g., blogs which required a password were excluded. A total of 14 blogs met inclusion criteria. Actions to …

Regional Heterogeneity And Diversity Of Astrocytes In Response To Hiv-1 Proteins And Morphine, Wen Chen

Theses and Dissertations

HIV-infected individuals who abuse opiates have been found to have a higher incidence and a faster progression of HIV encephalitis. Astrocytes, the major support cells in the CNS, are known to play a critical role in the HIV neuropathy. Although astrocytes tend not to be productively infected by the HIV-1 virus, dysregulation of their pro- and anti- inflammatory cytokines/chemokines secretion is usually neurotoxic. Glutamate transport in astrocytes is reported to be impaired as well, which result in extrasynaptic excitatory neurotransmitter accumulation and over stimulation of postsynaptic neurons. It is long known that astrocytes from different brain regions have diverse responses …

Machismo As A Determinant For Hiv/Std Risk Behavior Among Latino Msm, Jacqueline L. Sears

Theses and Dissertations

Objective: Male-to-male sexual contact is the most common mode of transmission for HIV among Latino men. Psychosocial factors such as machismo, homophobic discrimination, and internalized homophobia have been hypothesized to greatly impact sexual behaviors among Latinos. However, studies investigating the relationship between these psychosocial factors and risky sexual behaviors are limited. This study examined the impact of machismo on risky sexual behaviors among Latino Male who have Sex with Men (MSM).Methods: This study utilized data collected from 254 Latino MSM in 1999 from selected cities within Virginia. The analysis focused on respondent demographic characteristics, psychosocial factors, acculturation, and sexual risky …

Factors Associated With High Sexual Risk Behavior In Single Women, Thomas B. M. Leecost

Theses and Dissertations

Objective: This study was to identify factors associated with High Sexual Risk Behavior (HSRB) in single Afro American women seen in an Epidemiology/Sexual transmitted disease (EPID/STD) Clinic in Richmond, Virginia from January 2006 through April 2006.Method: Participants were 154 single women (no history of marriage) between the ages of 18-30 visiting the EPID/STD clinic for the first time.Demographic information was obtained from their records. A volunteer interview was given that contained 101 variables to evaluate for High Sexual Risk Behavior (HSRB). HSRB was defined to response 'yes' to the question, "During the past 3 months did you have sex with …

Lack Of Knowledge Of Mother-To-Child Transmission In Kenya Among Women Ages 15-49, Nisha Warrier

Theses and Dissertations

Purpose: The epidemic of mother-to-child transmission (MTCT) of HIV/AIDS in resource-poor countries is dramatic; it is responsible for nearly 90% of childhood infections. The primary purpose of analysis was to understand the distribution of factors and their association with lack of knowledge of MTCT in Kenya. In parallel, another aim was to identify the relationship between media, particularly frequency of radio exposure, and lack of knowledge.Methods: This study used the 2003 Kenya Demographic and Health Survey (DHS) collected for 8,195 women, ages 15-49. Descriptive analysis, univariate analysis, and logistic regression were completed on SPSS 14 software.Results: In the sample, 1151 …