Medicine and Health Sciences Commons^™

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

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

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 ^111.2GW^111.3 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 …

Acyclovir-Resistant Anogenital Herpes Simplex Virus In An Hiv Patient With Pseudoepitheliomatous Hyperplasia Resembling Squamous Cell Carcinoma, Jean Elizze M. Charles, Stephen E. Weis, Gregory A. Hosler

HCA Healthcare Journal of Medicine

Background

Herpes simplex virus (HSV) is a common infection. However, it may present atypically when patients are immunocompromised, such as with slowly expanding, long-lasting ulcerative or hypertrophic lesions. The histopathologic finding of pseudoepitheliomatous hyperplasia (PEH) can occur in a variety of situations where there is chronic inflammation and can be seen in patients with chronic HSV. Atypical presentations of HSV, particularly hypertrophic lesions with histopathologic findings of PEH, can be misinterpreted as squamous cell carcinoma, create difficulty in diagnosis and hinder appropriate treatment.

Case Description

We report a case of a 59-year-old female with a past medical history of human …

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 …

Preparing To Break Barriers: A Mixed Methods Exploration Of The Knowledge, Attitudes, And Perceptions Of Hiv, Prep, And Hiv Risk Behaviors Among Women Of Color In Miami, Florida, Amanda C. Ichite

FIU Electronic Theses and Dissertations

The U.S. HIV epidemic is characterized by regional, racial, and ethnic disparities. HIV rates are disproportionately higher in the South and Black and Hispanic populations are most impacted. Moreover, the intersectional identity of being a Black or Hispanic woman living in the South has been associated with profound disparities in HIV impact. Prior to the advent of the biomedical HIV prevention tool pre-exposure prophylaxis (PrEP) in 2012, women were limited in their options for female-controlled HIV prevention strategies. Despite the proven efficacy of PrEP, utilization in women is significantly lower than other at-risk groups. In the present study, secondary analysis …

Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler

FIU Electronic Theses and Dissertations

In the brain, HIV predominantly infects microglia/macrophages and astrocytes to a lesser extent. These cells form virus reservoirs with low levels of infection that are very hard to eradicate. Even though the use of cART increases survival rate in HIV patients, the virus persists as a chronic condition. cART is not able to effectively cross the BBB, control HIV replication, or attenuate inflammation in brain reservoirs. Therefore, the virus still causes neuronal dysfunction, pain-related pathology, and ultimately HAND. In this study, we decided to test the hypothesis that a serpin-derived small peptide, SP16, can serve as an anti-viral, anti-inflammatory, pro-survival, …

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 …

Hiv Antiretroviral Medication Neuropenetrance And Neurocognitive Outcomes In Hiv+ Adults: A Review Of The Literature Examining The Central Nervous System Penetration Effectiveness Score, Alyssa Arentoft, Katie Troxell, Karen Alvarez, Maral Aghvinian, Monica Rivera Mindt, Mariana Cherner, Kathleen Van Dyk, Jill Razani, Michaela Roxas, Melissa Gavilanes

All Faculty Open Access Publications

This literature review summarizes the existing research examining the CNS penetration effectiveness (CPE) score and neurocognitive outcomes (i.e., neuropsychological assessment and neurocognitive screening) in HIV+ individuals. Despite the effectiveness of Combined Antiretroviral Therapy (CART) in reducing mortality and morbidity in HIV and controlling viral replication, HIV often persists in the Central Nervous System (CNS), and rates of neurocognitive impairment remain higher than predicted in the post-CART era. The CPE score was developed to rank antiretroviral regimens on their ability to penetrate the CNS and potency in inhibiting the virus, and it has been examined in relation to neurocognitive functioning for …

Interventions For Prevention Of Non-Communicable Diseases Among Adolescents Living With Hiv: A Systematic Review, Eunice Ndirangu, Constance Shumba, Peter Gatiti, Bernard Mutwiri, Amina Abubakar

School of Nursing & Midwifery, East Africa

While the uptake of antiretroviral drugs has rapidly expanded among adolescents and adults living with HIV, research evidence suggests that people living with HIV have a higher risk of non-communicable diseases (NCDs). With more than 35% of the global burden of NCDs stemming from adolescence, there is a need to comprehend the existing evidence on early prevention, detection, and disease management, especially among the at-risk population. In line with the WHO Global Action Plan, 2013–2020 and “Best Buys”, recommendations on practical interventions for NCDs prevention, this systematic review seeks to synthesise evidence on the current interventions for preventing NCDs among …

Isolation And Characterization Of Α-Hcd7 Scfv Expressing Exosomes And Synthesis Of Hybrid Exosome-Liposome For Analyses, Sahil Patel

Biotechnology Theses

The goal of this thesis project is to isolate and characterize exosomes that express anti-human CD7 (α-hCD7) single chain variable fragment (scFv), which will be further utilized for T celltargeted gene editing. To reach this goal, exosomes from HEK 293 cells and Jurkat cells were isolated and characterized with different methodologies. To obtain α-hCD7 scFv-expressing exosomes, the HEK 293 cells were subjected to transfection of custom-plasmid pDisplay-αhCD7 scFv, and the expression of α-hCD7 scFv on the HEK 293-derived exosomes were then confirmed by immunogold staining, western blotting, and flow cytometry. To transfect 293 cells, calcium phosphate transfection was utilized, and …

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

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

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

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 …

Understanding Exosomal Extracellular Vesicles And Morphine In The Neuropathology Of Human Immunodeficiency Virus And Differential Zika Virus Strain-Associated Pathology, Allen Caobi

FIU Electronic Theses and Dissertations

Exosomal Extracellular Vesicles (xEVs), integral to intercellular communication and regulation of immune responses, have functional effects based on their contents, which they transport to neighboring cells. However, in the context of infection, EV cargo can be modulated, by either infected or uninfected cells. We hypothesize that CNS-associated neuropathology, is partially, due to the cargo transported by the exosomes. We theorize that the cargo released from infected cell-derived xEVs may either facilitate or inhibit viral neuropathogenicity. Here we investigated xEVs in the case of two neurotropic viruses, Zika virus (ZIKV) and Human Immunodeficiency Virus (HIV). The hallmark characteristic of ZIKV-infection is …

Examining The Effects Of Individual And Neighborhood Factors On Hiv Transmission Risk Potential Among People With Hiv, Semiu Olatunde Gbadamosi

FIU Electronic Theses and Dissertations

HIV transmission risk significantly increases in late-diagnosed HIV and at HIV viral load (VL) >1500 copies/mL. The objective of this dissertation was to examine factors associated with HIV transmission risk potential for persons with HIV (PWH) using measures of time from HIV infection to diagnosis and trajectories of VL suppression. Additionally, we sought to determine whether a single yearly VL measure—the current standard to track the HIV epidemic in the United States—is reliable in assessing viral suppression for PWH. The first study estimated the distribution of time from HIV infection to diagnosis in Florida using a CD4 depletion model and …

Decision-Analytic Models Using Reinforcement Learning To Inform Dynamic Sequential Decisions In Public Policy, Seyedeh Nazanin Khatami

Doctoral Dissertations

We developed decision-analytic models specifically suited for long-term sequential decision-making in the context of large-scale dynamic stochastic systems, focusing on public policy investment decisions. We found that while machine learning and artificial intelligence algorithms provide the most suitable frameworks for such analyses, multiple challenges arise in its successful adaptation. We address three specific challenges in two public sectors, public health and climate policy, through the following three essays. In Essay I, we developed a reinforcement learning (RL) model to identify optimal sequence of testing and retention-in-care interventions to inform the national strategic plan “Ending the HIV Epidemic in the US”. …

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 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 …