Immune System Diseases Commons^™

Epigenetic Mechanisms Underlying Hiv-Infection Induced Susceptibility Of Cd4+ T Cells To Enhanced Activation-Induced Fasl Expression And Cell Death., Smita Ghare, Paula M. Chilton, Aakarsha V. Rao, Swati Joshi-Barve, Paula Peyrani, Andrea Reyes-Vega, Craig J. Mcclain, Kendall Bryant, Robert L. Cook, Mathew Freiberg, Shirish Barve

Faculty and Staff Scholarship

Background:

Chronic immune activation and CD4⁺ T cell depletion are significant pathogenic features of HIV infection. Expression of Fas ligand (FasL), a key mediator of activation-induced cell death in T cells, is elevated in people living with HIV-1 infection (PLWH). However, the epigenetic mechanisms underlying the enhanced induction of FasL expression in CD4⁺ T lymphocytes in PLWH are not completely elucidated. Hence, the current work examined the effect of HIV infection on FasL promoter-associated histone modifications and transcriptional regulation in CD4⁺ T lymphocytes in PLWH.

Method:

Flow cytometric analysis was performed to examine the Fas-FasL expression on …

Molecular Virology Of Kshv In The Lymphocyte Compartment—Insights From Patient Samples And De Novo Infection Models, Farizeh Aalam, Jennifer Totonchy

Pharmacy Faculty Articles and Research

The incidence of Kaposi’s sarcoma-associated herpesvirus (KSHV)-associated Kaposi Sarcoma has declined precipitously in the present era of effective HIV treatment. However, KSHV-associated lymphoproliferative disorders although rare, have not seen a similar decline. Lymphoma is now a leading cause of death in people living with HIV (PLWH), indicating that the immune reconstitution provided by antiretroviral therapy is not sufficient to fully correct the lymphomagenic immune dysregulation perpetrated by HIV infection. As such, novel insights into the mechanisms of KSHV-mediated pathogenesis in the immune compartment are urgently needed in order to develop novel therapeutics aimed at prevention and treatment of KSHV-associated lymphoproliferations. …

From Caregiver To Patient And Back Again ... My Covid Experience, Marie B. Thornton

Journal of Interprofessional Practice and Collaboration

As a Registered Nurse and a member of the nursing faculty at a public university, my primary role and instinct is to be a caregiver. Here is my story about becoming a patient with COVID-19 and finally returning to be a caregiver once again.

Can Viruses Cause Lupus?, Stephen I. Reeder

Selected Honors Theses

Like so many autoimmune diseases, the exact cause of systemic lupus erythematosus (SLE) remains unknown. Evidence points to both genetics and environment playing roles in the onset of the disease, but neither acts independent of the other. Genetics are the easier of the two to study with recent advances in the field making it easier to isolate genes shared by individuals with the disease. However, genetic studies reveal that there is almost certainly an environmental component to the development of SLE. The underlying pathology and existing research on environmental contributors to the development of SLE suggest that viruses could potentially …

Haiti's Hiv Surveillance System: Past, Present, And Future, Chris Delcher, Ermane G. Robin, Daniella Myriam Pierre

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Adherence To Hiv Antiretroviral Therapy Among Pregnant And Postpartum Women During The Option B+ Era: 12-Month Cohort Study In Urban South Africa And Rural Uganda, Lynn T. Matthews, Catherine Orrell, Mwebesa B. Bwana, Alexander C. Tsai, Christina A. Psaros, Stephen Asiimwe, Gideon Amanyire, Nicholas Musinguzi, Kathleen Bell, David Bangsberg, Jessica E. Haberer

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction: We conducted a cohort study to understand patterns of anti-retroviral therapy (ART) adherence during pregnancy, postpartum and non-pregnancy follow-up among women initiating ART in public clinics offering Option B+ in rural Uganda and urban South Africa. Methods: We collected survey data, continuously monitored ART adherence (Wisepill), HIV-RNA and pregnancy tests at zero, six and twelve months from women initiating ART in Uganda and South Africa, 2015 to 2017. The primary predictor of interest was follow-up time categorized as pregnant (pregnancy diagnosis to pregnancy end), postpartum (pregnancy end to study exit) or non-pregnancy-related (neither pregnant nor postpartum). Fractional regression …

Insights From Individuals With Chronic Conditions In The Context Of Covid-19, B. Stephen Burton, Jonathan Patterson, Mackenzie Robinson, Dhiren Patel, Matt Allison, Kelly J. Brassil

Patient Experience Journal

The objective of this prospective survey series was to evaluate knowledge and concerns related to the COVID-19 pandemic among individuals with one or more chronic conditions, including cardiometabolic, autoimmune, respiratory and cancer diagnoses. Two surveys were distributed consisting of up to 55 items (March; n=1069) and up to 71 items (April, n=1126), with 24 items repeated from the first survey. Questions focused on healthcare access, barriers and concerns related to the COVID-19 virus. Descriptive analysis evaluated central tendencies, spread, and frequencies of the demographic data, disease states, and survey results within and between the two survey timepoints. Results from 416 …

Combined Effects Of Gender Affirmation And Economic Hardship On Vulnerability To Hiv: A Qualitative Analysis Among U.S. Adult Transgender Women., Larissa Jennings Mayo-Wilson, Eric G. Benotsch, Sheila R. Grigsby, Sarah Wagner, Fatmata Timbo, Tonia Poteat, Lauretta Cathers, Ashlee N. Sawyer, Shelby A. Smout, Rick S. Zimmerman

School of Nursing Faculty Publications

Background: Transgender women ("trans women"), particularly African-American and Latina trans women, have disproportionately high prevalence of HIV in the United States (U.S.). In order to decrease gender dysphoria and overcome discrimination, trans women affirm their gender through social and medical transition, often in contexts of economic hardship and sexual risk. This study qualitatively examined how gender-affirming behaviors enhance or diminish vulnerability to HIV in light of structural and economic barriers to gender transition.Methods: We conducted individual interviews with 19 adult trans women in two U.S. cities (Richmond, VA and St. Louis, MO) who reported one or more sexual risk behaviors …

Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott

Undergraduate Honors Theses

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …

Investigating The Interactions Between Individual Calmodulin And Hiv-1 Protein Domains, Riley K. Kendall, Jerry Larue

Student Scholar Symposium Abstracts and Posters

The World Health Organization found that 37.9 million people were living with HIV by the end of 2018. HIV is a virus that weakens the immune system through viral replication and the destruction of CD4⁺ T-cells, which are white blood cells that detect infection and make antibodies. A cure for HIV has not yet been discovered. HIV-1 contains a Gag polyprotein which regulates the stages of viral replication. Previous studies suggest that the myristoyl group of a matrix protein peptide found on the Gag polyprotein, MA, forms a complex with a calcium-binding, multifunctional regulatory protein called Calmodulin (CaM). CaM …

Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …

Tobacco/Hiv-1-Induced Myeloid Cell-Derived Extracellular Vesicles In Hiv-1 Pathogenesis, Sanjana Haque

Theses and Dissertations (ETD)

Introduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Super Learner Analysis Of Real-Time Electronically Monitored Adherence To Antiretroviral Therapy Under Constrained Optimization And Comparison To Non-Differentiated Care Approaches For Persons Living With Hiv In Rural Uganda, Alejandra E. Benitez, Nicholas Musinguzi, David Bangsberg, Mwebesa B. Bwana, Conrad Muzoora, Peter Hunt, Jeffrey N. Martin, Jessica E. Haberer, Maya L. Petersen

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction

Real‐time electronic adherence monitoring (EAM) systems could inform on‐going risk assessment for HIV viraemia and be used to personalize viral load testing schedules. We evaluated the potential of real‐time EAM (transferred via cellular signal) and standard EAM (downloaded via USB cable) in rural Uganda to inform individually differentiated viral load testing strategies by applying machine learning approaches.

Methods

We evaluated an observational cohort of persons living with HIV and treated with antiretroviral therapy (ART) who were monitored longitudinally with standard EAM from 2005 to 2011 and real‐time EAM from 2011 to 2015. Super learner, an ensemble machine learning method, …

Hiv Care Continuum Characteristics Among People With Opioid Use Disorder And Hiv In Vietnam: Baseline Results From The Bravo Study, Caroline King, Le Minh Giang, Gavin Bart, Lynn Elizabeth Kunkel, P. Todd Korthuis

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background

Little is known about patient characteristics that contribute to initiating antiretroviral therapy (ART) and achieving viral suppression among HIV people with opioid use disorder in Vietnam. The primary objective of this analysis was to evaluate associations between participant characteristics and the critical steps in the HIV care continuum of ART initiation and HIV viral suppression among people with opioid use disorder and HIV in Vietnam.

Methods

We assessed baseline participant characteristics, ART status, and HIV viral suppression (HIV RNA PCR < 200 copies/mL) enrolled in a clinical trial of HIV clinic-based buprenorphine versus referral for methadone among people with opioid use disorder in Vietnam. We developed logistic regression models to identify characteristics associated with ART status and HIV viral suppression.

Results

Among 283 study participants, 191 (67.5%) were prescribed ART at baseline, and 168 of those on ART (90%) …

Prevalence And Correlates Of Transactional Sex Among Women Of Low Socioeconomic Status In Portland, Or, Timothy Menza, Lauren Lipira, Amisha Bhattarai, Victoria Cali-De Leon, E. Roberto Orellana

School of Social Work Faculty Publications and Presentations

Background: Women who report transactional sex are at increased risk for HIV and other sexually transmitted infections (STIs). However, in the United States, social, behavioral, and trauma-related vulnerabilities associated with transactional sex are understudied and data on access to biomedical HIV prevention among women who report transactional sex are limited.

Methods: In 2016, we conducted a population-based, cross-sectional survey of women of low socioeconomic status recruited via respondent-driven sampling in Portland, Oregon. We calculated the prevalence and, assessed the correlates of, transactional sex using generalized linear models accounting for sampling design. We also compared health outcomes, HIV screening, and knowledge …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

Leveraging Technology To Blend Large-Scale Epidemiologic Surveillance With Social And Behavioral Science Methods: Successes, Challenges, And Lessons Learned Implementing The Unite Longitudinal Cohort Study Of Hiv Risk Factors Among Sexual Minority Men In The United States, H. Jonathon Rendina, Ali J. Talan, Nicola F. Tavella, Jonathan Lopez Matos, Ruben H. Jimenez, S. Scott Jones, Brian Salfas, Drew Westmoreland

Publications and Research

The use of digital technologies to conduct large-scale research with limited interaction (i.e., no in-person contact) and objective endpoints (i.e., biological testing) has significant potential for the field of epidemiology, but limited research to date has been published on the successes and challenges of such approaches. We analyzed data from a cohort study of sexual minority men across the United States, collected using digital strategies during a 10-month period from 2017 to 2018. Overall, 113,874 individuals were screened, of whom 26,000 were invited to the study, 10,691 joined the study, and 7,957 completed all enrollment steps, including return of a …

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

Graduate Theses/Dissertations

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …

Identification Of The Kaposi's Sarcoma-Associated Herpesvirus (Kshv) Surface Glycoprotein Targets Of Human Kshv-Specific Neutralizing Antibody Responses, Yasaman Mortazavi

School of Biological Sciences: Dissertations, Theses, and Student Research

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the etiological agent of Kaposi’s sarcoma (KS), and is also associated with two B cell malignancies, primary effusion lymphoma and multicentric Castleman's disease. The distribution of KSHV varies globally with high prevalence in some areas of sub-Saharan Africa (SSA), where seroprevalence can be as high as 80%. It is estimated that nearly 44,000 new cases of KS emerge annually globally, with the highest incidents occurring in Africa, where KSHV is endemic. Currently, there is no prophylactic vaccine against KSHV, and efforts to develop prophylactic vaccines have been limited. …

Treatment Of Podoconiosis With Complicating Polyinfections Within Rural African Villages: A Case Study, Amanda R. Beering, Abigail R. Florence, Soon Bahrami Md

Journal of Refugee & Global Health

This case study aims to provide a treatment plan for the treatment of podoconiosis with complicating polyinfections in a resource poor setting. A second objective is to help healthcare providers teach preventive measures to villagers in affected regions.

Eugenics In The 21st Century, Jessica Linn Chin

Dissertations, Theses, and Capstone Projects

Eugenics is the science of enhancing the human population through the management of breeding and hereditary traits. This thesis explores the history of eugenics and shows how eugenic practices continue in the 21^st century with advancements in technology and positive eugenic goals that can result in adverse effects on the human body and society. When Sir Francis Galton coined the term eugenics in 1883, he intended to improve British society with the use of positive eugenics. Galton used positive eugenics to encourage people with good mental and physical qualities to produce more children. He avoided negative eugenics, which involved …

Autoimmune Hepatitis In Patients With Human Immunodeficiency Virus Infection, Mohamad Mubder, Mohamed Azab, Mahendran Jayaraj, Chad Cross, Daisy Lankarani, Banreet Dhindsa, Jen-Jung Pan, Gordon Ohning

School of Medicine Faculty Research

Background: Liver disease in patients with HIV is common and typically has complex and multifactorial presentations that represent a major cause of morbidity and mortality. Autoimmune hepatitis (AIH) is rarely reported in patient with HIV and the disease course and clinical outcomes for treatment have not been well characterized. We are aiming to determine the patient characteristics, disease prevalence, and treatment outcomes from published articles of patients with HIV and AIH. Method: A systematic search of PubMed, Web of Science, and Google Scholar through February 20th, 2019 identified 15 studies that reported the outcomes of AIH in patients with HIV. …

Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire

Theses & Dissertations

Antiretroviral therapy (ART) requires lifelong daily dosing to suppress viral replication, restore or maintain immune function and improve quality of life. As an alternative, long-acting (LA) antiretrovirals (ARVs) aim to deliver therapeutic drug concentrations over an extended period, ultimately requiring monthly or even more extended dosing intervals. Specifically, the success of recent clinical trials examining LA cabotegravir and rilpivirine (CAB and RPV LA) highlight the advent of these novel HIV-1 therapeutics. Further optimization of LA dosage forms are required and rests upon improving dosing frequency, injection volumes and tissue distribution to viral compartments. To this end, we report the synthesis …

An Application Of The Modifiable Areal Unit Problem: Optimizing Cluster Method Parameters To Produce Predictive Data For Hiv Outbreaks, Connor J. Chato, Art Fy Poon

Western Research Forum

Background

A popular approach to study HIV outbreaks is to cluster cases based on genetic similarity. However, there is no widely-used statistical criterion which optimizes the parameters for sequence-based clustering methods. The relationship between a cluster-defining similarity threshold and it’s associated set of clusters can be analogized to the aggregation level in the Modifiable Areal Unit Problem (MAUP).

Hypothesis

Based on the selection of aggregation level for study partitions in MAUP, we present a statistical framework to optimize the similarity threshold for pairwise distance algorithm TN93 (http://github.com/veg/tn93). We hypothesize that defining this threshold includes case connections such that …

The Effect Of Disclosure On Adherence To Antiretroviral Therapy Among Adults Living With Hiv In Ethiopia: A Systematic Review And Meta-Analysis., Getenet Dessie, Fasil Wagnew, Henok Mulugeta, Dessalegn Amare, Dube Jara, Cheru Tesema Leshargie, Ayenew Negesse, Swati Rayasam, Sahai Burrowes

BACKGROUND: Several factors have been identified as being associated with increased adherence to antiretroviral therapy, including sero-status disclosure; however, studies examining the effect of disclosure on ART adherence in Ethiopia have had inconsistent findings. This systematic review and meta-analysis therefore aims to estimate the pooled effect of disclosure on adherence to ART among adults living with HIV in Ethiopia.

METHODS: We performed a systematic search for articles reporting on peer-reviewed, quantitative, English-language observational studies of reporting the association between self sero-status disclosure and good ART adherence in adults living with HIV/AIDS in Ethiopia during published from 2010 to 2015. We …

Male Determining Gene Nix May Bring An End To Transmission Of Diseases Through Mosquitoes, Mohammed Mahdi

Thinking Matters Symposium Archive

Female mosquitoes take blood from humans to gain protein needed to produce eggs, and in the process they can transmit viruses, such as Zika, Dengue, and chikungunya, or parasites, such as malaria. Male mosquitoes do not transmit diseases. This literature review will examine what is known about how sex is determined in mosquitoes and how this can be used to manipulate the females that spread diseases to humans. Using CRISPR Cas9, the lab of Zhijian Tu removed the Nix gene from mosquito embryos; all of these were feminized. Ectopic overexpression of Nix gene product in mosquito embryos caused even genetically …

Internalized Hiv Stigma, Art Initiation And Hiv-1 Rna Suppression In South Africa: Exploring Avoidant Coping As A Longitudinal Mediator, Valerie A. Earnshaw, Laura M. Bogart, Jean-Philippe Laurenceau, Brian T. Chan, Brendan G. Maughan-Brown, Janan Dietrich, Ingrid Courtney, Gugu Tshabalala, Catherine Orrell, Glenda E. Gray, David Bangsberg, Ingrid T. Katz

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction: Cross‐sectional evidence suggests that internalized HIV stigma is associated with lower likelihoods of antiretroviral therapy (ART) initiation and HIV‐1 RNA suppression among people living with HIV (PLWH). This study examined these associations with longitudinal data spanning the first nine months following HIV diagnosis and explored whether avoidant coping mediates these associations.

Methods: Longitudinal data were collected from 398 South African PLWH recruited from testing centres in 2014 to 2015. Self‐report data, including internalized stigma and avoidant coping (denying and distracting oneself from stressors), were collected one week and three months following HIV diagnosis. ART initiation at six months and …

Hla-C Downregulation By Hiv-1 Adapts To Host Hla Genotype, Nathaniel D. Batchel, Gisele Umviligihozo, Suzanne Pickering, Talia Mota, Hua Liang, Gregory Q. Del Prete, Pramita Chatterjee, Guinevere Q. Lee, Rasmi Thomas, Mark A. Brockman, Stuart Neil, Mary Carrington, Bosco M. Bwana, David Bangsberg, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

HIV-1 can downregulate HLA-C on infected cells, using the viral protein Vpu, and the magnitude of this downregulation varies widely between primary HIV-1 variants. The selection pressures that result in viral downregulation of HLA-C in some individuals, but preservation of surface HLA-C in others are not clear. To better understand viral immune evasion targeting HLA-C, we have characterized HLA-C downregulation by a range of primary HIV-1 viruses. 128 replication competent viral isolates from 19 individuals with effective anti-retroviral therapy, show that a substantial minority of individuals harbor latent reservoir virus which strongly downregulates HLA-C. Untreated infections display no change in …

Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland

Publications

A small percentage of babies born to Zika virus (ZIKV)-infected mothers' manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had …