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Full-Text Articles in Virus Diseases

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec Aug 2023

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec

School of Medicine Faculty Publications

Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …


Unknown Rectal Lesions: A Case Of Severe Proctitis Secondary To Mpox In The Setting Of Concomitant Hiv, Syphilis, Hsv, And Chlamydia, Nicole Robertson Mph, James Crosby Do, Cynthia R. Young Md, Msc, Anne E. Sayers Md, Nicholas J. Van Sickles Md Aug 2023

Unknown Rectal Lesions: A Case Of Severe Proctitis Secondary To Mpox In The Setting Of Concomitant Hiv, Syphilis, Hsv, And Chlamydia, Nicole Robertson Mph, James Crosby Do, Cynthia R. Young Md, Msc, Anne E. Sayers Md, Nicholas J. Van Sickles Md

ePublications of Emerging Medical Research Scholars

Introduction:

Mpox emerged as a public health crisis with limited research describing co-occurring HIV and sexually transmitted infections (STIs). We present a case of severe proctitis secondary to Mpox with concomitant HIV (Human Immunodeficiency Virus), syphilis, HSV (Herpes Simplex Virus), and chlamydia and review presentation, diagnosis, treatment, and prevention of Mpox with concurrent STIs.

Case Presentation:

34-year-old male living with HIV (LWH) presenting with worsening rectal pain, multiple anal papules, and fever. His laboratory workup revealed simultaneous positive results for orthopoxvirus, chlamydia, and HSV-1 PCR. We initiated tecovirimat due to rectal involvement and uncontrolled pain. He subsequently developed lesions on …


Under One Roof – An Integrated Clinic For Substance Use Disorder And Viral Hepatitis/Hiv Treatment, Sarah Hipkens, Emily Caron, Wendy Craig, Kinna Thakarar Aug 2023

Under One Roof – An Integrated Clinic For Substance Use Disorder And Viral Hepatitis/Hiv Treatment, Sarah Hipkens, Emily Caron, Wendy Craig, Kinna Thakarar

Journal of Maine Medical Center

Introduction: Integration of viral hepatitis/HIV care and substance use disorder (SUD) treatment has been shown to improve patient outcomes, but data are lacking in rural states like Maine. Our study objective was to assess the baseline characteristics and outcomes of patients with SUD who receive combined substance use and viral hepatitis/HIV treatment at a recently established “Bridge Program” in our rural state.

Methods: We conducted a retrospective chart review of patients enrolled in the Bridge Program between January 2020 and November 2021. We then performed a descriptive analysis of demographics, health characteristics, preventive services, and treatment outcomes.

Results: A total …


Independent Effects Of Hiv And Antiretroviral Therapy On The Oral Microbiome Identified By Multivariate Analyses, Clifford J. Beall, Elizabeth A. Lilly, Carolina Granada, Kelly Treas, Kenneth R. Dubois, Shahr B. Hashmi, Jose A. Vazquez, Michael E. Hagensee, Ann L. Griffen, Eugene J. Leys, Paul L. Fidel Apr 2023

Independent Effects Of Hiv And Antiretroviral Therapy On The Oral Microbiome Identified By Multivariate Analyses, Clifford J. Beall, Elizabeth A. Lilly, Carolina Granada, Kelly Treas, Kenneth R. Dubois, Shahr B. Hashmi, Jose A. Vazquez, Michael E. Hagensee, Ann L. Griffen, Eugene J. Leys, Paul L. Fidel

School of Dentistry Faculty Publications

The oral microbiome is an important predictor of health and disease. We recently reported significant yet modest effects of HIV under highly active antiretroviral therapy (ART) on the oral microbiome (bacterial and fungal) in a large cohort of HIV-positive (HIV+) and matched HIV-negative (HIV-) individuals. As it was unclear whether ART added to or masked further effects of HIV on the oral microbiome, the present study aimed to analyze the effects of HIV and ART independently, which also included HIV- subjects on preexposure prophylaxis (PrEP) therapy. Cross-sectional analyses of the effect of HIV devoid of ART (HIV+ ART- versus matched …


Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista Apr 2023

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …


Attitudes Towards Hiv Testing In Pregnant And Non-Pregnant Women, Sashia Malone, Susan Greene Jan 2023

Attitudes Towards Hiv Testing In Pregnant And Non-Pregnant Women, Sashia Malone, Susan Greene

South Atlantic Division GME Research Day 2023

No abstract provided.


Perspectives On The Use Of Molecular Hiv Data For Public Health, Margaret Watson Jan 2023

Perspectives On The Use Of Molecular Hiv Data For Public Health, Margaret Watson

College of Graduate Studies: Theses & Dissertations

Background. Effective HIV treatment and pre-exposure prophylaxis can drastically reduce the risk of acquiring HIV and prevent most future transmission, but these advances are not accessible to many who could most benefit from them. Advances in use of molecular sequence data to inform prevention efforts, paired with supportive interventions, have the potential to identify clusters of rapid HIV transmission and focus prevention resources toward areas of highest need. Although molecular cluster detection has been successfully used in other areas of public health, advocates for people with HIV have raised concerns about the application of this approach because of HIV …


A Systematic Review To Study The Global Patterns And Policies Of Hiv Harm Reduction Programs And Their Impact Among People Who Inject Drugs, Noura Shaltout, Rania Soliman, Lamia Refaey, Rim Ghazal, Mirna Atteya, Nahla Elmedany Jan 2023

A Systematic Review To Study The Global Patterns And Policies Of Hiv Harm Reduction Programs And Their Impact Among People Who Inject Drugs, Noura Shaltout, Rania Soliman, Lamia Refaey, Rim Ghazal, Mirna Atteya, Nahla Elmedany

Papers, Posters, and Presentations

Aim: This study aims to provide an updated estimate of HIV prevalence among people who inject drugs (PWID) globally, as well as investigate different policies and methods for applying harm reduction. This article focuses on the two major and the most frequently used harm reduction techniques, Syringe-Service Programs (SSPs) and Opioid Agonist Therapy (OAT). Methods: A comprehensive systematic review was undertaken across multiple international databases during the period of (August-December 2021). For studies conducted before 2005, we used data from a previous published systematic review. Thirty-six studies were included, including studies that had performed HIV testing and had a confirmed …


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 Jan 2023

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 …


Sheprep: Examining The Influence Of The Messaging And The Messenger Associated With Prep Uptake Among African American Women, Christian C. Spears Jan 2023

Sheprep: Examining The Influence Of The Messaging And The Messenger Associated With Prep Uptake Among African American Women, Christian C. Spears

College of Graduate Studies: Theses & Dissertations

African American Women (AAW) make up less than 15% of the female population in the United States but account for over 50% of new HIV diagnoses among females. This largely preventable health disparity can be mitigated by advocating and prescribing Pre-exposure Prophylaxis (PrEP), a preventive HIV medication, to persons at risk. Despite advances in medication options, there are less than 13% of Black people who could benefit from having been prescribed PrEP, and limited research and promotion on the effectiveness of PrEP for AAW. The “ShePrEP Study” aimed to assess awareness, perceptions, and receptivity toward PrEP among AAW. This study …


Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal Dec 2022

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …


Cost Utility Of Supporting Family-Based Care To Prevent Hiv And Deaths Among Orphaned And Separated Children In East Africa: A Markov Model–Based Simulation, Marta Wilson-Barthes, Paula Braitstein, Allison Delong, David Ayuku, Lukoye Atwoli, Edwin Sang, Omar Galárraga Dec 2022

Cost Utility Of Supporting Family-Based Care To Prevent Hiv And Deaths Among Orphaned And Separated Children In East Africa: A Markov Model–Based Simulation, Marta Wilson-Barthes, Paula Braitstein, Allison Delong, David Ayuku, Lukoye Atwoli, Edwin Sang, Omar Galárraga

Internal Medicine, East Africa

Purpose: Strengthening family-based care is a key policy response to the more than 15 million orphaned and separated children who have lost 1 or both parents in sub-Saharan Africa. This analysis estimated the cost-effectiveness of family-based care environments for preventing HIV and death in this population.

Design: We developed a time-homogeneous Markov model to simulate the incremental cost per disability-adjusted life year (DALY) averted by supporting family-based environments caring for orphaned and separated children in western Kenya. Model parameters were based on data from the longitudinal OSCAR’s Health and Well-Being Project and published literature. We used a societal perspective, …


Dependence On A Variable Residue Limits The Breadth Of An Hiv Mper Neutralizing Antibody, Despite Convergent Evolution With Broadly Neutralizing Antibodies, Cathrine Scheepers, Prudence Kgagudi, Nonkululeko Mzindle, Elin S. Gray, Thandeka Moyo-Gwete, Bronwen E. Lambson, Brent Oosthuysen, Batsirai Mabvakure, Nigel J. Garrett, Salim S.Abdool Karim, Lynn Morris, Penny L. Moore Sep 2022

Dependence On A Variable Residue Limits The Breadth Of An Hiv Mper Neutralizing Antibody, Despite Convergent Evolution With Broadly Neutralizing Antibodies, Cathrine Scheepers, Prudence Kgagudi, Nonkululeko Mzindle, Elin S. Gray, Thandeka Moyo-Gwete, Bronwen E. Lambson, Brent Oosthuysen, Batsirai Mabvakure, Nigel J. Garrett, Salim S.Abdool Karim, Lynn Morris, Penny L. Moore

Research outputs 2022 to 2026

Broadly neutralizing antibodies (bNAbs) that target the membrane-proximal external region (MPER) of HIV gp41 envelope, such as 4E10, VRC42.01 and PGZL1, can neutralize > 80 % of viruses. These three MPER-directed monoclonal antibodies share germline antibody genes (IGHV1 - 69 and IGKV3 - 20) and form a bNAb epitope class. Furthermore, convergent evolution within these two lineages towards a 111.2GW111.3 motif in the CDRH3 is known to enhance neutralization potency. We have previously isolated an MPER neutralizing antibody, CAP206 - CH12, that uses these same germline heavy and light chain genes but lacks breadth (neutralizing only 6 % of …


Nanotherapeutics And Hiv: Four Decades Of Infection Canvass The Quest For Drug Development Using Nanomedical Technologies, Bhupender S. Chhikara, Nirpendra Singh, Poonam, Parveen Bazard, Rajender S. Varma, Keykavous Parang Aug 2022

Nanotherapeutics And Hiv: Four Decades Of Infection Canvass The Quest For Drug Development Using Nanomedical Technologies, Bhupender S. Chhikara, Nirpendra Singh, Poonam, Parveen Bazard, Rajender S. Varma, Keykavous Parang

Pharmacy Faculty Articles and Research

We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part …


Impact Of The Covid-19 Pandemic On The Care Continuum Of Youth Living With Hiv: Qualitative Study Of The Scale It Up Program Clinical Sites, Tyra Dark, Sitaji Gurung, Mary Dooley, Kit N. Simpson, Seyram A. Butame, Sylvie Naar Jun 2022

Impact Of The Covid-19 Pandemic On The Care Continuum Of Youth Living With Hiv: Qualitative Study Of The Scale It Up Program Clinical Sites, Tyra Dark, Sitaji Gurung, Mary Dooley, Kit N. Simpson, Seyram A. Butame, Sylvie Naar

Publications and Research

The study objective was to explore the impact of COVID-19 pandemic restrictions on the clinics’ ability to provide continuous healthcare services to youth (15–24 years) living with HIV (YLWH). One focused semi-structured interview was conducted with each HIV clinic site—resulting in ten interviews. Data were analyzed using thematic analysis techniques assisted by NVIVO coding software and themes indicating barriers and facilitators to providing uninterrupted healthcare were elicited. Six themes were identified that affected the care continuum of YLWH: Timeframe of clinic preparation to address COVID-19 restrictions; impact on treatment cascade monitoring data; impact on patient care; impact on staff and …


Use Of Long-Acting Injectable Cabotegravir And Rilpivirine As An Alternative For Treatment In Hiv Positive Patients, Aravindh Nirmalan Apr 2022

Use Of Long-Acting Injectable Cabotegravir And Rilpivirine As An Alternative For Treatment In Hiv Positive Patients, Aravindh Nirmalan

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

Mantsios A, Murray M, Karver TS, et al. Efficacy and Freedom: Patient Experiences with the Transition from Daily Oral to Long-Acting Injectable Antiretroviral Therapy to Treat HIV in the Context of Phase 3 Trials. AIDS Behav. 2020;24(12):3473-3481. https://doi.org/10.1007/s10461-020-02918-x

for a young adult patient struggling with adherence.


Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth Apr 2022

Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth

Honors Theses

As the total number of people living with HIV continues to rise across the world, an effective HIV treatment is still sought after. While modern-day advanced therapies exist for mitigating much of the negative effects of HIV, the virus remains evasive and problematic in the central nervous system. Thus, even with treatment, many people living with HIV continue to suffer from a plethora of symptoms. However, a large proportion of HIV-positive patients claim to feel a reduction in those persevering symptoms after cannabis usage. This anecdotal evidence has sparked interest in the efficacy of cannabis constituents for HIV therapy. This …


Emerging Viral Diseases: Generation Z'S Outlook, Ian Mcwhorter Apr 2022

Emerging Viral Diseases: Generation Z'S Outlook, Ian Mcwhorter

Honors Projects

Generation Z differs notably from previous generations like Baby Boomers or Generation X. In recent years, young adults have been persisting through the COVID-19 pandemic, though not unscathed. This paper seeks to answer the following question: How does Generation Z differ in its outlook on Viral diseases compared to previous generations? Using a series of three surveys conducted on three seperate Viral diseases (HIV, Zika, and COVID 19), it was found that while Generation Z has improved in its ability to combat Viral outbreaks due to factors like high digital literacy, other factors such as poorer mental health show that …


Feasibility Of Using Electronic Health Records For Cascade Monitoring And Cost Estimates In Implementation Science Studies In The Adolescent Trials Network For Hiv/Aids Interventions, Tyra Dark, Kit N. Simpson, Sitaji Gurung, Amy L. Pennar, Marshall Chew, Sylvie Naar Apr 2022

Feasibility Of Using Electronic Health Records For Cascade Monitoring And Cost Estimates In Implementation Science Studies In The Adolescent Trials Network For Hiv/Aids Interventions, Tyra Dark, Kit N. Simpson, Sitaji Gurung, Amy L. Pennar, Marshall Chew, Sylvie Naar

Publications and Research

Background:One of the most difficult areas in the fight against HIV/AIDS is reaching out to youth aged 13 to 24 years. The proportion of youth living with HIV/AIDS on antiretroviral therapy (ART) and who are virally undetectable is low, highlighting significant challenges for reaching the Joint United Nations Program on HIV targets.

Objective:This study aimed to assess the feasibility of obtaining key clinical indicators and monitoring treatment, viral suppression, and retention components of the youth HIV treatment cascade in Adolescent Trials Network for HIV/AIDS Interventions clinics using electronic health record (EHR) downloads and to provide baseline characteristics for the study …


Age-Associated Gut Dysbiosis, Marked By Loss Of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites In Older People Living With Hiv., Smita Ghare, Richa Singhal, Vaughn Bryant, Sabina Gautam, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Andrea Reyes-Vega, Dushan Ghooray, Craig J. Mcclain, Kristi Hoffman, Joseph Petrosino, Kendall Bryant, Varand Govind, Ronald Cohen, Robert L. Cook, Shirish Barve Feb 2022

Age-Associated Gut Dysbiosis, Marked By Loss Of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites In Older People Living With Hiv., Smita Ghare, Richa Singhal, Vaughn Bryant, Sabina Gautam, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Andrea Reyes-Vega, Dushan Ghooray, Craig J. Mcclain, Kristi Hoffman, Joseph Petrosino, Kendall Bryant, Varand Govind, Ronald Cohen, Robert L. Cook, Shirish Barve

Faculty and Staff Scholarship

Background:

Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined.

Methods:

Older people living with HIV infection (PLWH, aged 50–70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome …


Living Positive, Cheyann Harris, Emani King Mack Dec 2021

Living Positive, Cheyann Harris, Emani King Mack

Capstones

A short documentary by Emani King Mack & Cheyann Harris, that focuses on Black men who are living with HIV. This film features the stories of Malik Davon, Jah Love, and Melchizedek Roberson to destigmatize, empower, and set a new precedent in media on how to cover people living with HIV.

Link to capstone: https://cheyannharris.wixsite.com/livingpositive


Does Hiv Status Confer A Higher Risk Of Acquiring Covid-19? Using Clinical Decision Science To Combat Patients’ Anxiety, Camilo Guzman Oct 2021

Does Hiv Status Confer A Higher Risk Of Acquiring Covid-19? Using Clinical Decision Science To Combat Patients’ Anxiety, Camilo Guzman

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

del Amo J, Polo R, Moreno S, et al. “Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy.” Annals of Internal Medicine. 2020;173(7):536-541. doi.org/10.7326/m20-3689

for a patient with HIV and concerns about COVID-19 for immunocompromised individuals.


Factors That Influence Perception Of Hiv Risk And Willingness To Use Pre-Exposure Prophylaxis In People Who Inject Drugs, Daria Egorova, Anny Fenton, Kinna Thakarar Aug 2021

Factors That Influence Perception Of Hiv Risk And Willingness To Use Pre-Exposure Prophylaxis In People Who Inject Drugs, Daria Egorova, Anny Fenton, Kinna Thakarar

Journal of Maine Medical Center

Introduction: Sexual and injection behaviors increase the risk of HIV transmission in people who inject drugs (PWID). We aimed to determine the prevalence of sexual and drug behaviors that increase HIV risk in PWID hospitalized for infections related to injection drug use in Maine. We also examined factors that influenced their perception of HIV risk and willingness to take pre-exposure prophylaxis (PrEP).

Methods: We surveyed 101 PWID with infections related to injection drug use who were hospitalized at 4 hospitals in Maine. T-tests assessed differences in means of bacterial infection risk scores and willingness to take PrEP based on different …


Human Apobec3 Variations And Viral Infection, Shiva Sadeghpour, Saeideh Khodaee, Mostafa Rahnama, Hamzeh Rahimi, Diako Ebrahimi Jul 2021

Human Apobec3 Variations And Viral Infection, Shiva Sadeghpour, Saeideh Khodaee, Mostafa Rahnama, Hamzeh Rahimi, Diako Ebrahimi

Plant Pathology Faculty Publications

Human APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) enzymes are capable of inhibiting a wide range of endogenous and exogenous viruses using deaminase and deaminase-independent mechanisms. These enzymes are essential components of our innate immune system, as evidenced by (a) their strong positive selection and expansion in primates, (b) the evolution of viral counter-defense mechanisms, such as proteasomal degradation mediated by HIV Vif, and (c) hypermutation and inactivation of a large number of integrated HIV-1 proviruses. Numerous APOBEC3 single nucleotide polymorphisms, haplotypes, and splice variants have been identified in humans. Several of these variants have been reported to be associated …


Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew May 2021

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 …


Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner May 2021

Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner

Theses & Dissertations

Despite effective regimens of combination antiretroviral therapy, individuals with HIV are still at higher risk for developing forms of cognitive impairment, with one of the most common behavioral abnormalities to manifest being motor dysfunction. This is an important consideration, as deficits in motor control likely contribute to higher-order cognitive impairments, which together, lead to functional dependencies in the ever-growing aging population of HIV-infected adults. While the neuroanatomical bases of motor dysfunction have recently been illuminated in people living with HIV (PLWH), there remains an open question regarding the molecular processes supporting the circuit-level neuronal dynamics that potentially serve these behavioral …


Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb May 2021

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 …


Neurocognitive Impairment In People Living With Human Immunodeficiency Virus (Hiv): Risk Factors And Mortality, Zaeema Naveed May 2021

Neurocognitive Impairment In People Living With Human Immunodeficiency Virus (Hiv): Risk Factors And Mortality, Zaeema Naveed

Theses & Dissertations

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) persists in people living with HIV (PLWH) with clinical and public health implications. Studies have generated inconsistent results regarding etiological factors for NCI in PLWH and a brief user-friendly predictive tool is desirable in clinical practice to assess the probability of having NCI in PLWH. Furthermore, factors associated with clinically meaningful decline in neurocognitive status and survival disadvantage for patients with NCI are understudied in the post-cART era. The goal of this dissertation was to investigate factors associated with baseline NCI and neurocognitive decline and the association …


Simian Varicella Virus Antibody Response In Recombinant Svv-Siv Immunized Primates, Kiser Horne May 2021

Simian Varicella Virus Antibody Response In Recombinant Svv-Siv Immunized Primates, Kiser Horne

Honors Theses

Since its emergence in the early 1980’s HIV has killed approximately 32 million people, and continues to kill over half a million people every year. Significant research into potential vaccines and cures for HIV has been ongoing for decades but has been largely unsuccessful. One of the more promising technologies that is being investigated to develop an HIV vaccine is recombinant vaccine technology. The study presented in this thesis aims to use simian varicella virus (SVV) and simian immunodeficiency virus (SIV) to act as a model for recombinant vaccine development. If a recombinant SVV-SIV vaccine can be proven safe and …


Hiv Tat Protein Activates Plasma Kallikrein-Kinin System In Hiv-1 Tat Transgenic Mice, Logan Sneed Apr 2021

Hiv Tat Protein Activates Plasma Kallikrein-Kinin System In Hiv-1 Tat Transgenic Mice, Logan Sneed

Honors Theses

Human Immunodeficiency Viruses are a group of lentiviruses that have seen a lot of study ever since their discovery. HIV-1, the most common and virulent form of the virus, has proven to be quite deadly when untreated, so any research into the mechanisms of HIV pathogenesis and replication could have major medical applications all over the world. HIV-1 is a sexually transmitted virus that compromises the hosts immune system and eventually leads to the patient developing AIDS, a life-threatening condition that nearly half of people infected with HIV will develop within ten years. Our study sets out to determine exactly …