Download or read book The Dynamics of Intermittent Latent Reservoir Stimulation as a Tool for Eradication of Human Immunodeficiency Virus HIV Infection written by Ellen Rice and published by . This book was released on 2012 with total page 84 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Dynamics of the HIV 1 Latent Reservoir written by Mark David Pankau and published by . This book was released on 2019 with total page 96 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human immunodeficiency virus type 1 (HIV) has caused more than 35 million deaths world-wide and contributes significantly to the global burden of disease. Currently, the only effective treatment to suppress viral replication and prevent HIV transmission is combination antiretroviral therapy (ART), which prevents HIV from infecting new cells. Despite the efficacy of ART, long lived latently infected cells persist, with an estimated half-life of 44 months, and circulate throughout the infected host necessitating life-long treatment. These cells, known as the latent reservoir, contain an integrated form of the HIV genome (HIV DNA) that is transcriptionally silent, but can reactivate to produce virus. Therefore, interruption of ART inevitably leads to viral recrudescence stemming from the latent reservoir. Studying the latent reservoir is difficult because these cells contain no known biomarkers and do not always produce replication competent virus upon cellular activation. Additionally, latent reservoir cells are rare, and many proviral genomes contain defects that prevent them from producing replication competent virus. They do however confound efforts to measure the replication competent reservoir. Understanding the dynamics and correlates of reservoir seeding will be essential to develop novel cure strategies that target this latent reservoir. There is limited data on the dynamics of reservoir seeding throughout HIV infection, the impact of treatment interruption on reservoir size, and whether antibodies can play a role in limiting reservoir seeding. I focused my thesis on characterizing the seeding dynamics of latent reservoir cells containing HIV DNA (HIV DNA Reservoir) to better understand when the latent reservoir was generated and how it changed following treatment interruption. In the first part of this thesis I adapt, optimize, and validate a molecular based assay to quantitate HIV DNA from latently infected cells, as well as develop a novel cell line to detect replication competent HIV reactivated from latent reservoirs. In the second part of this thesis I demonstrate that the HIV DNA reservoir is limited by early ART and does not significantly increase following randomization to short treatment interruption in a cohort of Kenyan infants, suggesting that short treatment interruption studies may pose little risk to reservoir reseeding. I also examine the role of ADCC activity in preventing re-seeding of the latent reservoir and demonstrate that ADCC activity does not correlate with change in HIV DNA reservoir size following treatment interruption. Finally, I demonstrate that the HIV DNA reservoir is comprised mostly of viral variants circulating just prior to ART initiation, suggesting that during untreated infection the HIV DNA reservoir decays at a much faster rate than during suppressive ART. Together, these data demonstrate that the HIV DNA reservoir is limited by early ART, is not significantly reseeded with short treatment interruption, and that contrary to previous assumptions about reservoir dynamics, is decaying at a significantly faster rate pre-ART than after ART initiation, and suggest that targeting the HIV latent reservoir prior to early ART initiation may be an effective strategy to limit reservoir size, and that short treatment interruption can limit re-seeding of the latent reservoir.

Download or read book HIV 1 Latency written by Guido Silvestri and published by Springer. This book was released on 2018-10-11 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume summarizes recent advances in understanding the mechanisms of HIV-1 latency, in characterizing residual viral reservoirs, and in developing targeted interventions to reduce HIV-1 persistence during antiretroviral therapy. Specific chapters address the molecular mechanisms that govern and regulate HIV-1 transcription and latency; assays and technical approaches to quantify viral reservoirs in humans and animal models; the complex interchange between viral reservoirs and the host immune system; computational strategies to model viral reservoir dynamics; and the development of therapeutic approaches that target viral reservoir cells. With contributions from an interdisciplinary group of investigators that cover a broad spectrum of subjects, from molecular virology to proof-of-principle clinical trials, this book is a valuable resource for basic scientists, translational investigators, infectious-disease physicians, individuals living with HIV/AIDS and the general public.

Download or read book Spatiotemporal Dynamics of HIV Infection written by Matthew Carl Strain and published by . This book was released on 2002 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Viral Persistence Latent Reservoir and Blips written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4 T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.

Download or read book Exploring Novel Approaches to Eliminate HIV Reservoirs to Achieve a Cure for HIV written by Renee Marije Van Der Sluis and published by Frontiers Media SA. This book was released on 2021-04-07 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Strategies to Facilitate the Eradication of the HIV 1 Reservoir written by Shariq Mujib and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Nearly 40 million individuals are currently living with Human Immunodeficiency Virus type 1 (HIV-1) infection globally and more than 70 million deaths can be attributed to the pathogen so far. HIV-1 primarily infects CD4 T cells leading to their widespread destruction that eventually manifests as Acquired Immunodeficiency Syndrome (AIDS), characterized by debilitating immune failure that gives rise to opportunistic malignancies resulting in death. Daily lifelong administration of antiretroviral therapy known as HAART is the only treatment for HIV-1 infection and adds several years of life if adherence is maintained; but treatment alone does not cure infection. However, despite HAART therapy, HIV-infected individuals exhibit chronic inflammation that is negatively associated with health outcomes. Additionally, mutations give rise to drug resistant viral strains. Therefore, developing a cure remains a top priority. However, HIV-1 constantly evades the immune response and establishes a persistent lifelong viral reservoir making it challenging to cure. In this thesis, I detail three unique strategies to facilitate eradication of the viral reservoir. Specifically, we demonstrated that HIV-1 Nef blockade enhanced the elimination of latently HIV-1-infected CD4 T cells by peptide-expanded autologous CD8 T cells. Nef blockade has never been tested as means to eradicate HIV-1 and represents a novel approach. We further demonstrated that expanded CD8 T cells more efficiently recognize autologous endogenous virus from CD4 T cells undergoing bryostatin-1-mediated virus reactivation in a "shock and kill" approach. Lastly, we discovered that bnAb recognition of HIV-1 envelopes on the surface of infected cells is highly variable and particularly the V1/V2 targeting bnAbs were capable of not only recognition of targets but of induction of antibody-mediated elimination of HIV-1-infected CD4 T cells. All experiments presented here were conducted on primary human cells for physiological relevance and in order to capture the ability of ex vivo immune cells to recognize and kill virus-infected cells. The next step with each of the proposed mechanisms to eliminate the viral reservoir is to assess their safety and efficacy in vivo in order to develop a cure against HIV/AIDS.

Download or read book HIV Cure Through Eradication of Viral Reservoirs written by Maher M. Elsheikh and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistence of the latent HIV reservoir is the main obstacle in preventing or curing HIV. Even though a combination of antiretroviral therapy (cART) is effective in controlling the virus by suppressing its replication and infectivity to below detection levels, cART cannot eliminate the latent reservoir, and must be taken for life. After encountering HIV, some infected CD4+ T cells revert to a resting state and persist as memory T cells that remain quiescent while containing the stable HIV proviral DNA (latent reservoir). With a stable and long-lived reservoir, HIV remains a global health problem because the proviral DNA is transcriptionally silent but is capable of producing infectious particles when cART is interrupted. According to WHO, more than 34 million people died due to AIDS over the past three decades, and about 37 million are currently living with it. In addition, there are approximately two million new cases each year. HIV-infected individuals do not achieve complete immunologic reconstitution because viral suppression is incomplete, and immune activation occurs chronically. The inability of cART to eradicate HIV from latent viral reservoirs necessitates the development of novel therapeutic approaches to eradicate the virus from infected individuals so that cART can be discontinued. The goal of this work was to investigate innovative experimental approaches to eradicate the latent HIV reservoir by targeting specific molecular mechanisms within the PKC/NF-kB and p-TEFb signaling pathways of HIV-infected resting memory CD4+ T cells involved in viral replication and silencing during the HIV life cycle. This goal was successfully achieved by implementing two independent experimental approaches: 1) Eliminating HIV infected cells by inducing reactivation of latent HIV and targeting the activated cells for apoptosis (sterilizing cure). 2) Inducing permanent silencing of HIV in the latent viral reservoir by shutting down the HIV replication machinery, which could permanently inhibit viral replication in the infected cells (functional cure). Subsequently, we were able to identify latency reactivating agents and apoptosis inducing agents that, when used in combination, dramatically reduced the latent HIV reservoir. We were also able to identify several viral silencing agents (VSA) that target essential cellular and viral proteins within the NF-[kappa]B and PKC signaling pathways in infected cells. These VSAs curtail HIV proviral transcription and elongation, which permanently silence latent HIV for multi-generations. They were also effective in reducing viral transcription. Although our data demonstrated that this combination treatment has great potential as an effective anti-HIV therapy, additional testing using larger sample sizes and multiple latency cell models that target various cell reservoirs is needed in order to demonstrate that this therapy is effective and fully functional against various viral sanctuaries in the human body, and is capable of completely eliminating the reservoir with minimal cytotoxicity. Nevertheless, this was an important initial step to prove that our proposed strategy can be successful and should be evaluated further. This novel treatment strategy has the possibility of eliminating the latent HIV reservoir to achieve a drug-free remission and to cure HIV in the future.

Download or read book Immunopathogenesis of HIV Infection written by Anthony S. Fauci and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: During the last 5 years, major advances have been made in our understanding of the pathogenesis of human immunodeficiency virus (HIV) disease and in the development of new potent antiviral agents. With regard to HIV pathogenesis, several recent observations have not only changed our perspectives of HIV disease, but have been critical for the design of therapeutic strategies.

Download or read book Virus Dynamics Mathematical Principles of Immunology and Virology written by Martin Nowak and published by Oxford University Press, UK. This book was released on 2000-11-23 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This groundbreaking book describes the emerging field of theoretical immunology, in particular the use of mathematical models to describe the spread of infectious diseases within patients. It reveals fascinating insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. Structured around the examples of HIV/AIDS and hepatitis B, Nowak and May show how mathematical models can help researchers to understand the detailed dynamics of infection and the effects of antiviral therapy. Models are developed to describe the dynamics of drug resistance, immune responses, viral evolution and mutation, and to optimise the design of therapy and vaccines. - ;We know, down to the tiniest details, the molecular structure of the human immunodeficiency virus (HIV). Yet despite this tremendous accomplishment, and despite other remarkable advances in our understanding of individual viruses and cells of the immune system, we still have no agreed understanding of the ultimate course and variability of the pathogenesis of AIDS. Gaps in our understanding like these impede our efforts towards developing effective therapies and preventive vaccines. Martin Nowak and Robert M May describe the emerging field of theoretical immunology in this accessible and well- written text. Using mathematical modelling techniques, the authors set out their ideas about how populations of viruses and populations of immune system cells may interact in various circumstances, and how infectious diseases spread within patients. They explain how this approach to understanding infectious diseases can reveal insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. The book is structured around the examples of HIV/AIDS and Hepatitis B virus, although the approaches described will be more widely applicable. The authors use mathematical tools to uncover the detailed dynamics of the infection and the effects of antiviral therapy. Models are developed to describe the emergence of drug resistance, and the dynamics of immune responses, viral evolution, and mutation. The practical implications of this work for optimisation of the design of therapy and vaccines are discussed. The book concludes with a glance towards the future of this fascinating, and potentially highly useful, field of study. - ;... an excellent introduction to a field that has the potential to advance substantially our understanding of the complex interplay between virus and host - Nature

Download or read book Models of Protection Against HIV SIV written by Gianfranco Pancino and published by Academic Press. This book was released on 2011-12-02 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: A successful vaccine for the prevention and/or immunotherapy against HIV/AIDS is one of the prominent challenges of the 21st century. To date, all human vaccine trials against this virus/disease have resulted in failure, or at best have shown very low efficacy. The scientific community dealing with HIV/AIDS has unanimously proposed a focus on basic science, with the intention of identifying correlates of protection that can serve as guides in developing and evaluating vaccine preparation. However, Nature seems to have already found several ways of dealing with infections by HIV and related primate lentiviruses, either by resisting infection or, once infected, avoiding immune damage and immunodeficiency. Models of Protection Against HIV/SIV will allow for an in-depth reflection on the perspectives for vaccine and therapy research derived from important recent studies. It will be authored by some of the most well known specialists in the field of HIV resistance/protection: including F. Barré-Sinoussi (2008 Nobel Prize for Medicine winner), B. Walker, S. Rowland-Jones, A. Telenti, M. Lederman and F. Plummer. This book is structured in a unique way, looking at three models of resistance/protection separately and then comparing the models against one another to provide its readership with a detailed examination of the research that is most predominant in the search for a vaccine. This structure presents the information in an easy-to-understand format and gives the book a cross-discipline appeal -- an important reference for those in the scientific community, medical care, public health and academia alike. Provides extensive descriptions and comparisons on the different models of protection agains HIV/AIDS Comprehensive writing and illustrations Contributors are among the most eminent specialists in the field

Download or read book Critical Needs and Gaps in Understanding Prevention Amelioration and Resolution of Lyme and Other Tick Borne Diseases written by Institute of Medicine and published by National Academies Press. This book was released on 2011-07-01 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: A single tick bite can have debilitating consequences. Lyme disease is the most common disease carried by ticks in the United States, and the number of those afflicted is growing steadily. If left untreated, the diseases carried by ticks-known as tick-borne diseases-can cause severe pain, fatigue, neurological problems, and other serious health problems. The Institute of Medicine held a workshop October 11-12, 2010, to examine the state of the science in Lyme disease and other tick-borne diseases.

Download or read book Handbook of Clinical Obstetrics written by E. Albert Reece, MD, PhD, MBA and published by John Wiley & Sons. This book was released on 2008-04-15 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this quick reference handbook for obstetricians and gynecologists and primary care physicians is designed to complement the parent textbook Clinical Obstetrics: The Fetus & Mother The third edition of Clinical Obstetrics: The Fetus & Mother is unique in that it gives in-depth attention to the two patients – fetus and mother, with special coverage of each patient. Clinical Obstetrics thoroughly reviews the biology, pathology, and clinical management of disorders affecting both the fetus and the mother. Clinical Obstetrics: The Fetus & Mother - Handbook provides the practising physician with succinct, clinically focused information in an easily retrievable format that facilitates diagnosis, evaluation, and treatment. When you need fast answers to specific questions, you can turn with confidence to this streamlined, updated reference.

Download or read book Principles and Practice of College Health written by John A. Vaughn and published by Springer Nature. This book was released on 2020-12-04 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: This unique and comprehensive title offers state-of-the-art guidance on all of the clinical principles and practices needed in providing optimal health and well-being services for college students. Designed for college health professionals and administrators, this highly practical title is comprised of 24 chapters organized in three sections: Common Clinical Problems in College Health, Organizational and Administrative Considerations for College Health, and Population and Public Health Management on a College Campus. Section I topics include travel health services, tuberculosis, eating disorders in college health, and attention deficit hyperactivity disorder among college students, along with several other chapters. Subsequent chapters in Section II then delve into topics such as supporting the health and well-being of a diverse student population, student veterans, health science students, student safety in the clinical setting, and campus management of infectious disease outbreaks, among other topics. The book concludes with organizational considerations such as unique issues in the practice of medicine in the institutional context, situating healthcare within the broader context of wellness on campus, organizational structures of student health, funding student health services, and delivery of innovative healthcare services in college health. Developed by a renowned, multidisciplinary authorship of leaders in college health theory and practice, and coinciding with the founding of the American College Health Association 100 years ago, Principles and Practice of College Health will be of great interest to college health and well-being professionals as well as college administrators.

Download or read book Occupational Health and Safety in the Care and Use of Research Animals written by Committee on Occupational Safety and Health in Research Animal Facilities and published by National Academies Press. This book was released on 1997-06-23 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt: Much has been written about the care of research animals. Yet little guidance has appeared on protecting the health and safety of the people who care for or use these animals. This book, an implementation handbook and companion to Guide For the Care and Use of Laboratory Animals, identifies principles for building a program and discusses the accountability of institutional leaders, managers, and employees for a program's success. It provides a detailed description of risks-- physical and chemical hazards, allergens and zoonoses, and hazards from experiments--which will serve as a continuing reference for the laboratory. The book offers specific recommendations for controlling risk through administrative procedures, facility design, engineering controls, and periodic evaluations. The volume focuses on the worker, with detailed discussions of work practices, the use of personal protective gear, and the development of an emergency response plan. This handbook will be invaluable to administrators, researchers, and employees in any animal research facility. It will also be of interest to personnel in zoos, animal shelters, and veterinary facilities.

Download or read book Public Health Significance of Urban Pests written by Xavier Bonnefoy and published by World Health Organization. This book was released on 2008 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second half of the 20th century and the beginning of the 21st century witnessed important changes in ecology, climate and human behaviour that favoured the development of urban pests. Most alarmingly, urban planners now face the dramatic expansion of urban sprawl, in which city suburbs are growing into the natural habitats of ticks, rodents and other pests. Also, many city managers now erroneously assume that pest-borne diseases are relics of the past. All these changes make timely a new analysis of the direct and indirect effects of present-day urban pests on health. Such an analysis should lead to the development of strategies to manage them and reduce the risk of exposure. To this end, WHO invited international experts in various fields - pests, pest-related diseases and pest management - to provide evidence on which to base policies. These experts identified the public health risk posed by various pests and appropriate measures to prevent and control them. This book presents their conclusions and formulates policy options for all levels of decision-making to manage pests and pest-related diseases in the future. [Ed.]

Download or read book Biodiversity and Human Health written by Francesca Grifo and published by Island Press. This book was released on 1997-02-01 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The implications of biodiversity loss for the global environment have been widely discussed, but only recently has attention been paid to its direct and serious effects on human health. Biodiversity loss affects the spread of human diseases, causes a loss of medical models, diminishes the supplies of raw materials for drug discovery and biotechnology, and threatens food production and water quality. Biodiversity and Human Health brings together leading thinkers on the global environment and biomedicine to explore the human health consequences of the loss of biological diversity. Based on a two-day conference sponsored by the National Institutes of Health, the National Science Foundation, and the Smithsonian Institution, the book opens a dialogue among experts from the fields of public health, biology, epidemiology, botany, ecology, demography, and pharmacology on this vital but often neglected concern. Contributors discuss the uses and significance of biodiversity to the practice of medicine today, and develop strategies for conservation of these critical resources. Topics examined include: the causes and consequences of biodiversity loss emerging infectious diseases and the loss of biodiversity the significance and use of both prescription and herbal biodiversity-derived remedies indigenous and local peoples and their health care systems sustainable use of biodiversity for medicine an agenda for the future In addition to the editors, contributors include Anthony Artuso, Byron Bailey, Jensa Bell, Bhaswati Bhattacharya, Michael Boyd, Mary S. Campbell, Eric Chivian, Paul Cox, Gordon Cragg, Andrew Dobson, Kate Duffy-Mazan, Robert Engelman, Paul Epstein, Alexandra S. Fairfield, John Grupenhoff, Daniel Janzen, Catherine A. Laughin, Katy Moran, Robert McCaleb, Thomas Mays, David Newman, Charles Peters, Walter Reid, and John Vandermeer. The book provides a common framework for physicians and biomedical researchers who wish to learn more about environmental concerns, and for members of the environmental community who desire a greater understanding of biomedical issues.