Infectious Disease Commons^™

Patient-Reported Outcomes Through 1 Year Of An Hiv-1 Clinical Trial Evaluating Long-Acting Cabotegravir And Rilpivirine Administered Every 4 Or 8 Weeks (Atlas-2m), Vasiliki Chounta, Edgar T. Overton, Anthony Mills, Susan Swindells, Paul D. Benn, Simon Vanveggel, Rodica Van Solingen-Ristea, Yuanyuan Wang, Krischan J. Hudson, Mark S. Shaefer, David A. Margolis, Kimberly Y. Smith, William R. Spreen

Journal Articles: Infectious Diseases

BACKGROUND: Advances in HIV-1 therapeutics have led to the development of a range of daily oral treatment regimens, which share similar high efficacy rates. Consequently, more emphasis is being placed upon the individual's experience of treatment and impact on quality of life. The first long-acting injectable antiretroviral therapy for HIV-1 (long-acting cabotegravir + rilpivirine [CAB + RPV LA]) may address challenges associated with oral treatment for HIV-1, such as stigma, pill burden/fatigue, drug-food interactions, and adherence. Patient-reported outcomes (PROs) collected in an HIV-1 clinical trial (ATLAS-2M; NCT03299049) comparing participants' experience with two dosing regimens (every 4 weeks [Q4W] vs. every …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …

Clinical Consequences And Determinants Of False Positive Blood Cultures In Adult Hospitalized Patients, Sidra Liaquat

Theses & Dissertations

Blood cultures are the gold standard for detecting blood stream infections. However, in the US, 0.6-6% of all blood cultures get contaminated leading to adverse clinical outcomes such as unnecessarily prolonged hospital stay and antibiotic therapy. Using electronic medical records, we explored the clinical outcomes and patient-specific risk factors of contaminated blood cultures in an era where rapid blood culture testing was being utilized to provide blood culture results within hours. Rapid blood culture test results can help clinicians in early and more effective management of patients with contaminated blood cultures, thus improving clinical outcomes. We also studied the impact …

Fire Service Covid-19 Infection Prevention And Control Policy Comparison, Saaddedine Dichari

Theses & Dissertations

To date, there have been over 2.7 million deaths and more than 126 million cases attributed to the COVID-19 pandemic (JHU, 2021). This pandemic has affected nearly every aspect of daily life. Among those impacted are U.S. firefighters, as they provide many services beyond simply extinguishing structure fires and are frequently dual certified as emergency medical technicians. Many of the victims of this pandemic have relied on first responders to provide them with emergency medical care and hospital transport. When caring for these infected patients, firefighters have an increased risk of exposure and must be provided with adequate …

Multi-Level Considerations For Optimal Implementation Of Long-Acting Injectable Antiretroviral Therapy To Treat People Living With Hiv: Perspectives Of Health Care Providers Participating In Phase 3 Trials, Andrea Mantsios, Miranda Murray, Tahilin S. Karver, Wendy Davis, Noya Galai, Princy Kumar, Susan Swindells, U. Fritz Bredeek, Rafael Rubio García, Antonio Antela, Santiago Cenoz Gomis, Miguel Pascual Bernáldez, Maggie Czarnogorski, Krischan Hudson, Nicki Walters, Deanna Kerrigan

Journal Articles: Infectious Diseases

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings.

METHODS: This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M …

The Promise Of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are The Data?, Kimberly Scarsi, Susan Swindells

Journal Articles: Infectious Diseases

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community …

A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells

Journal Articles: Infectious Diseases

During the COVID-19 pandemic, HIV clinics had to transform care delivery for people with HIV (PWH). We developed a multifaceted telehealth implementation strategy and monitored number of out of care patients (OOC), medical visit frequency (MVF), gap in care (GiC) and viral suppression (VS), and compared measures to baseline data. Between April and October 2020, 1559 visits were scheduled; 328 (21%) were missed, and 63 (4%) were new to care. Of the remaining 1168 follow-up visits, 412 (35%) were telehealth visits. As of October 2020, there were 53 patients OOC, MVF was 55% and GiC was 24% compared to 34, …

Pandemic Driven Innovation: Development Of An Alternative Respiratory Pathogen Self-Collection Device, Thang Nguyen

Theses & Dissertations

The SARS-CoV-2 virus outbreak has underscored numerous weak links in our biodefense countermeasures against highly communicable diseases. Many believe it was our lack of an effective testing model that allowed the virus to become a global pandemic within a short period. The gold standard collection method for the SARS-CoV-2 virus involves mechanical debridement of the nasopharyngeal cavity with a stiff swab applicator, which has been known to cause pain and injury to patients, subsequently resulting in low patient acceptance of the procedure. Due to the invasive nature of the nasopharyngeal swab collection method, it may not be conducive to the …

Nontuberculous Mycobacterium (Ntm) Infection In Aquatic Workers With Purified Protein Derivative (Ppd) And Gold Quantiferon Tests., Lavanya Ravipati, Sarah A. Howard

Graduate Medical Education Research Journal

Background: Nontuberculous mycobacteria (NTM) infections are commonly caused by Mycobacterium marinum and fortuitum with M. marinum more likely to cause skin infections. Aquatic environments are a potential source of contact with M. marinum and fortuitum. Patients with NTM infections may present with positive tuberculin purified protein derivative (PPD) and/or gold QuantiFERON tests. However, PPD cannot differentiate between NTM infection and other tuberculous infections caused by different mycobacterial strains. We present a patient a marine biologist who was asymptomatic and presented for further evaluation as she has a h/o positive PPD and gold QuantiFERON test.

Methods: Patient informed consent was …

Customized Blister Packaging For Patients Living With Hiv: Assessment Of Patient Attitudes And Satisfaction, Holly Groteluschen, Harlan Sayles, Rebecca Osborn, Joshua P. Havens, Sara Bares, Jasmine R. Marcelin

Graduate Medical Education Research Journal

Adherence to antiretroviral medication results in reduced HIV transmission and improved health outcomes, yet challenges with medication adherence remain. A Collaborative Care Program was developed with a community pharmacy integrating a multi-dose adherence packaging service. We surveyed program participants to assess their satisfaction with this program and found an overall positive sentiment toward the program, that the program helped with reducing missed doses, and all patients would recommend the program to others.

Surprisingly Low Levels Of Measles Immunity In Persons With Hiv: A Seroprevalence Survey In A United States Hiv Clinic, Lindsey Rearigh, Jennifer O'Neill, Maureen Kubat, Harlan Sayles, Susan Swindells, Sara Bares

Journal Articles: Infectious Diseases

Background: Measles outbreaks have become increasingly common due to deteriorating vaccination rates, fluctuating herd immunity, and varying antibody decline. Limited knowledge exists regarding prevalence and risk factors associated with measles seronegativity among persons with HIV (PWH).

Methods: This was a cross-sectional study conducted at an academic HIV clinic in Omaha, Nebraska. Participants were screened for the presence of measles IgG antibody. Demographic and clinical information was obtained through electronic medical record review. Simple and multivariable logistic regressions were performed to identify risk factors for measles seronegativity.

Results: Three hundred fifty-one participants were enrolled, with a measles seroprevalence rate of 70.3%. …

Structural Magnetic Resonance Imaging As A Diagnostic Biomarker Of Hiv-Associated Neurocognitive Disorders (Hand), Mikki Schantell

Capstone Experience: Master of Public Health

Objective: The goal of this study was to do an exploratory analysis to determine if gray matter brain volumes and cortical thickness measures obtained from structural magnetic resonance imaging (sMRI) can discriminate people with HIV-associated neurocognitive disorders (HAND), neurocognitively unimpaired people with HIV (NU PWH), and HIV-negative controls (HIV- controls) using linear discriminant analyses.

Methods: A total of 231 participants, including 110 PWH and 121 HIV- controls, completed a neuropsychological (NP) battery and an sMRI protocol. The bilateral gray matter volumes and cortical thickness brain regions were analyzed using 18 linear discriminant models to assess the discriminability of gray matter …

Planning And Facilitating The Training Of Emergency Medical Services On The Safe Transport Of Patients With Highly Infectious Diseases, Mohammed Alhallaf

Theses & Dissertations

Emergency Medical Services (EMS) personnel are the first line of treatment and are the first exposed health care workers to infectious diseases (IDs). Consequently, the EMS setting is a relatively vulnerable environment for disease transmission and cross-contamination. Also, serious and emerging IDs, such as highly pathogenic viral hemorrhagic fevers and novel Coronaviruses, in a time of increased globalization, require comprehensive EMS training and preparedness. This project had the objective of identifying best practices for the EMS transport of patients with IDs. The methods for this project were done in two phases. In the first stage, we …

Sé Un Héroe Tú También, Samantha S. Rohe, Sophie Cemaj

Books: Pediatrics

This children's book explains COVID-19 and how to decrease the incidence of transmissions.

Be A Hero Too, Samantha S. Rohe, Sophie Cemaj

Books: Pediatrics

This children's book explains COVID-19 and how to decrease the incidence of transmissions.

Improving Antimicrobial Stewardship Programs In Small Community Hospitals Through An Assessment And Feedback Model, Philip Chung, Kate Tyner, Scott Bergman, Terry Micheels, Mark Rupp, Michelle Schwedhelm, Maureen Tierney, Muhammad Salman Ashraf, Trevor Van Schooneveld

Posters and Presentations: Nebraska ASAP

Small community hospitals often lack expertise and resources for antimicrobial stewardship program implementation. Using an assessment-and-feedback model, Nebraska ASAP performed onsite assessment of antimicrobial stewardship efforts in 5 small community hospitals and provided facility specific feedback on implementation/augmentation of antimicrobial stewardship program. As a result of this model, participating small community hospitals were able to increase the number of antimicrobial stewardship core elements implemented while reducing antibiotic use and incidence of CDI.

Controlling Latent Tb Tuberculosis Infection In High-Burden Countries: A Neglected Strategy To End Tb, Gavin J. Churchyard, Susan Swindells

Journal Articles: Infectious Diseases

In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries.

Acceptability And Feasibility Of A Pharmacist-Led Hiv Pre-Exposure Prophylaxis (Prep) Program In The Midwestern United States, Joshua P. Havens, Kimberly Scarsi, Harlan Sayles, Donald G. Klepser, Susan Swindells, Sara H. Bares

Journal Articles: Infectious Diseases

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services.

METHODS: Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and two community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended CDC guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized and participant satisfaction and pharmacist acceptability with the P-PrEP …

Patient Care In High-Level Containment Care Units: In A Resourced Setting, Angela M. Vasa, Kate C. Boulter, Jolene M. Horihan, David S. Cates, Craig A. Piquette, James N. Sullivan, Daniel W. Johnson, Angela L. Hewlett

Books and Book Chapters: Nebraska Medicine

Vasa, A., Boulter, K., Horihan, Cates, D., Piquette, C., Sullivan, J., Johnson, D, & Hewlett, A. (2019). Patient Care in High-Level Containment Care Units. In T. Cieslak, M. Kortepeter, C. Kratochvil, & J. Lawler (Eds.), Nebraska Isolation and Quarantine Manual (pp. 87-101). Lincoln, NE: University of Nebraska Press.

Determinants Of Facilitated Health Insurance Enrollment For Patients With Hiv Disease, And Impact Of Insurance Enrollment On Targeted Health Outcomes., Renae Furl, Shinobu Watanabe-Galloway, Elizabeth Lyden, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: The introduction of the Affordable Care Act (ACA) has provided unprecedented opportunities for uninsured people with HIV infection to access health insurance, and to examine the impact of this change in access. AIDS Drug Assistance Programs (ADAPs) have been directed to pursue uninsured individuals to enroll in the ACA as both a cost-saving strategy and to increase patient access to care. We evaluated the impact of ADAP-facilitated health insurance enrollment on health outcomes, and demographic and clinical factors that influenced whether or not eligible patients enrolled.

METHODS: During the inaugural open enrollment period for the ACA, 284 Nebraska ADAP …

A Pharmacist-Led Medication Switch Protocol In An Academic Hiv Clinic: Patient Knowledge And Satisfaction, Sarah S. Lee, Joshua P. Havens, Harlan R. Sayles, Jennifer L. O'Neill, Anthony T. Podany, Susan Swindells, Kimberly K. Scarsi, Sara H. Bares

Journal Articles: Infectious Diseases

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF's recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored.

METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration's (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with …

Frequently Identified Gaps In Antibiotic Stewardship Programs In Critical Access Hospitals, Philip Chung, Regina Nailon, Kate Tyner, Sue Beach, Scott Bergman, Margaret Drake, Teresa Fitzgerald, Elizabeth Lyden, Mark Rupp, Michelle Schwedhelm, Maureen Tierney-Brenran, Trevor Van Schooneveld, Muhammad Salman Ashraf

Posters and Presentations: Nebraska ASAP

Background: Nebraska (NE) Infection Control Assessment and Promotion Program (ICAP) is a CDC funded project. ICAP team works in collaboration with NE Department of Health and Human Services (NEDHHS) to assess and improve infection prevention and control programs (IPCP) in various health care settings including resource limited settings like critical access hospitals (CAH). Little is known about the existing gaps in antimicrobial stewardship programs (ASP) of CAH. Hence, we decided to study the current level of ASP activities and factors associated with these activities in CAH.

Methods: NE ICAP conducted on-site surveys in 36 CAH from October 2015 to February …

Aberrant Neuronal Dynamics During Working Memory Operations In The Aging Hiv-Infected Brain., Tony W. Wilson, Amy L. Proskovec, Elizabeth Heinrichs-Graham, Jennifer O'Neill, Kevin R. Robertson, Howard S. Fox, Susan Swindells

Journal Articles: Infectious Diseases

Impairments in working memory are among the most prevalent features of HIV-associated neurocognitive disorders (HAND), yet their origins are unknown, with some studies arguing that encoding operations are disturbed and others supporting deficits in memory maintenance. The current investigation directly addresses this issue by using a dynamic mapping approach to identify when and where processing in working memory circuits degrades. HIV-infected older adults and a demographically-matched group of uninfected controls performed a verbal working memory task during magnetoencephalography (MEG). Significant oscillatory neural responses were imaged using a beamforming approach to illuminate the spatiotemporal dynamics of neuronal activity. HIV-infected patients were …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …

A Survey Of Tuberculosis Infection Control Practices At The Nih/Niaid/Daids-Supported Clinical Trial Sites In Low And Middle Income Countries., Catherine Godfrey, Gail Tauscher, Sally Hunsberger, Melissa Austin, Lesley Scott, Jeffrey T. Schouten, Anne F. Luetkemeyer, Constance Benson, Robert Coombs, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement.

METHODS: A survey was developed that assessed IC activities in three domains: facility …

Predictors And Outcomes Of Mycobacterium Tuberculosis Bacteremia Among Patients With Hiv And Tuberculosis Co-Infection Enrolled In The Actg A5221 Stride Study., John A. Crump, Xingye Wu, Michelle A. Kendall, Prudence D. Ive, Johnstone J. Kumwenda, Beatriz Grinsztejn, Ute Jentsch, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: We evaluated predictors and outcomes of Mycobacterium tuberculosis bacteremia among participants undergoing baseline mycobacterial blood culture in the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with later ART among HIV-infected patients suspected of having tuberculosis with CD4-positive T-lymphocyte counts (CD4 counts)/mm(3). We conducted a secondary analysis comparing participants with respect to presence or absence of M. tuberculosis bacteremia.

METHODS: Participants with a baseline mycobacterial blood culture were compared with respect to the presence or absence of M. tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were identified and participant outcomes were compared by mycobacteremia status.

RESULTS: …