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HIV mathematical modeling

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https://www.readbyqxmd.com/read/28980928/optimizing-expression-of-antiviral-cyanovirin-n-homology-gene-using-response-surface-methodology-and-protein-structure-prediction
#1
H Lotfi, M A Hejazi, M K Heshmati, S A Mohammadi, N Zarghami
Cyanovirin-N (CVN) is well known as an anti-HIV protein. The efficient production of low cost microbicides for preventing the HIV-infection  has lately become a requirement worldwide. The aim of the present study was to optimize the expression of antiviral Cyanovirin-N homology gene found in the indigenous strain of Nostoc ellipsospourum LZN using Response Surface Methodology (RSM) and Protein Structure Analysis. Optimization of three induction factors (IPTG concentration (0.1, 0.55 and 1mM), temperature for bacterial growth (20, 28...
September 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28970973/multi-scale-immunoepidemiological-modeling-of-within-host-and-between-host-hiv-dynamics-systematic-review-of-mathematical-models
#2
Nargesalsadat Dorratoltaj, Ryan Nikin-Beers, Stanca M Ciupe, Stephen G Eubank, Kaja M Abbas
OBJECTIVE: The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level. BACKGROUND: While within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models is an emerging method to infer the synergistic dynamics of HIV at the individual and population levels...
2017: PeerJ
https://www.readbyqxmd.com/read/28940123/short-term-antiretroviral-treatment-recommendations-based-on-sensitivity-analysis-of-a-mathematical-model-for-hiv-infection-of-formula-see-text-cells
#3
Ana-Maria Croicu, Angela M Jarrett, N G Cogan, M Yousuff Hussaini
HIV infection is one of the most difficult infections to control and manage. The most recent recommendations to control this infection vary according to the guidelines used (US, European, WHO) and are not patient-specific. Unfortunately, no two individuals respond to infection and treatment quite the same way. The purpose of this paper is to make use of the uncertainty and sensitivity analysis to investigate possible short-term treatment options that are patient-specific. We are able to identify the most significant parameters that are responsible for ART outcome and to formulate some insights into the ART success...
September 22, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28922356/mathematical-modeling-and-quantitative-analysis-of-hiv-1-gag-trafficking-and-polymerization
#4
Yuewu Liu, Xiufen Zou
Gag, as the major structural protein of HIV-1, is necessary for the assembly of the HIV-1 sphere shell. An in-depth understanding of its trafficking and polymerization is important for gaining further insights into the mechanisms of HIV-1 replication and the design of antiviral drugs. We developed a mathematical model to simulate two biophysical processes, specifically Gag monomer and dimer transport in the cytoplasm and the polymerization of monomers to form a hexamer underneath the plasma membrane. Using experimental data, an optimization approach was utilized to identify the model parameters, and the identifiability and sensitivity of these parameters were then analyzed...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28904953/nonpaternity-and-half-siblingships-as-objective-measures-of-extramarital-sex-mathematical-modeling-and-simulations
#5
Ryosuke Omori, Nico Nagelkerke, Laith J Abu-Raddad
BACKGROUND: Understanding the epidemiology of HIV and other sexually transmitted infections (STIs) requires knowledge of sexual behavior, but self-reported behavior has limitations. We explored the reliability and validity of nonpaternity and half-siblings ratios as biomarkers of current and past extramarital sex. METHODS: An individual-based Monte Carlo simulation model was constructed to describe partnering and conception in human populations with a focus on Sub-Saharan Africa (SSA)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28894444/modeling-kick-kill-strategies-toward-hiv-cure
#6
REVIEW
Esteban A Hernandez-Vargas
Although combinatorial antiretroviral therapy (cART) potently suppresses the virus, a sterile or functional cure still remains one of the greatest therapeutic challenges worldwide. Reservoirs are infected cells that can maintain HIV persistence for several years in patients with optimal cART, which is a leading obstacle to eradicate the virus. Despite the significant progress that has been made in our understanding of the diversity of cells that promote HIV persistence, many aspects that are critical to the development of effective therapeutic approaches able to purge the latent CD4+ T cell reservoir are poorly understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878083/how-germinal-centers-evolve-broadly-neutralizing-antibodies-the-breadth-of-the-follicular-helper-t-cell-response
#7
Rob J De Boer, Alan S Perelson
Many HIV-1 infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years, and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest affinity receptors tend to acquire the most antigen from the FDC network, and present the highest density of cognate peptides to follicular helper T cells (Tfh), which provide survival signals to the B cell. BnAbs are therefore only expected to evolve when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than other lineages of more specific B cells...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28874236/funding-antiretroviral-treatment-for-hiv-positive-temporary-residents-in-australia-prevents-transmission-and-is-inexpensive
#8
Richard T Gray, Jo Watson, Aaron J Cogle, Don E Smith, Jennifer F Hoy, Lisa A Bastian, Robert Finlayson, Fraser M Drummond, Bill Whittaker, Matthew G Law, Kathy Petoumenos
Background: The aim of this study is to estimate the reduction in new HIV infections and resultant cost outcomes of providing antiretroviral treatment (ART) through Australia's 'universal access' health scheme to all temporary residents with HIV infection living legally in Australia, but currently deemed ineligible to access subsidised ART via this scheme. Methods: A mathematical model to estimate the number of new HIV infections averted and the associated lifetime costs over 5 years if all HIV-positive temporary residents in Australia had access to ART and subsidised medical care was developed...
September 6, 2017: Sexual Health
https://www.readbyqxmd.com/read/28870213/test-and-treat-approach-to-hiv-aids-a-primer-for-mathematical-modeling
#9
REVIEW
Kyeongah Nah, Hiroshi Nishiura, Naho Tsuchiya, Xiaodan Sun, Yusuke Asai, Akifumi Imamura
The public benefit of test-and-treat has induced a need to justify goodness for the public, and mathematical modeling studies have played a key role in designing and evaluating the test-and-treat strategy for controlling HIV/AIDS. Here we briefly and comprehensively review the essence of contemporary understanding of the test-and-treat policy through mathematical modeling approaches and identify key pitfalls that have been identified to date. While the decrease in HIV incidence is achieved with certain coverages of diagnosis, care and continued treatment, HIV prevalence is not necessarily decreased and sometimes the test-and-treat is accompanied by increased long-term cost of antiretroviral therapy (ART)...
September 5, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28807188/the-global-burden-of-tuberculosis-mortality-in-children-a-mathematical-modelling-study
#10
Peter J Dodd, Courtney M Yuen, Charalambos Sismanidis, James A Seddon, Helen E Jenkins
BACKGROUND: Tuberculosis in children is increasingly recognised as an important component of the global tuberculosis burden, with an estimated 1 million cases in 2015. Although younger children are vulnerable to severe forms of tuberculosis disease, no age-disaggregated estimates of paediatric tuberculosis mortality exist, and tuberculosis has never been included in official estimates of under-5 child mortality. We aimed to produce a global mortality burden estimate in children using a complementary approach not dependent on vital registration data...
September 2017: Lancet Global Health
https://www.readbyqxmd.com/read/28762130/modelling-coupled-within-host-and-population-dynamics-of-formula-see-text-and-formula-see-text-hiv-infection
#11
Edna Chilenje Manda, Faraimunashe Chirove
Most existing models have considered the immunological processes occurring within the host and the epidemiological processes occurring at population level as decoupled systems. We present a new model using continuous systems of non linear ordinary differential equations by directly linking the within host dynamics capturing the interactions between Langerhans cells, CD4[Formula: see text] T-cells, R5 HIV and X4 HIV and the without host dynamics of a basic compartmental HIV/AIDS model. The model captures the biological theories of the cells that take part in HIV transmission...
July 31, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28747624/number-of-infection-events-per-cell-during-hiv-1-cell-free-infection
#12
Yusuke Ito, Azaria Remion, Alexandra Tauzin, Keisuke Ejima, Shinji Nakaoka, Yoh Iwasa, Shingo Iwami, Fabrizio Mammano
HIV-1 accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution. Previous mathematical modeling approaches demonstrated that differences in target cell susceptibility can explain the non-randomness, both in the context of direct cell-to-cell transmission, and in the context of free virus transmission (Q...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747167/combined-interventions-to-reduce-hiv-incidence-in-kwazulu-natal-a-modelling-study
#13
Stéphanie Blaizot, Helena Huerga, Benjamin Riche, Tom Ellman, Amir Shroufi, Jean-François Etard, René Ecochard
BACKGROUND: Combined prevention interventions, including early antiretroviral therapy initiation, may substantially reduce HIV incidence in hyperendemic settings. Our aim was to assess the potential short-term impact of combined interventions on HIV spreading in the adult population of Mbongolwane and Eshowe (KwaZulu-Natal, South Africa) using sex- and age-specific scenarios, and age-targeted interventions. METHODS: A mathematical model was used with data on adults (15-59 years) from the Mbongolwane and Eshowe HIV Impact in Population Survey to compare the effects of various interventions on the HIV incidence rate...
July 26, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28743606/the-botanical-drug-substance-crofelemer-as-a-model-system-for-comparative-characterization-of-complex-mixture-drugs
#14
Peter A Kleindl, Jian Xiong, Asha Hewarathna, Olivier Mozziconacci, Maulik K Nariya, Adam C Fisher, Eric J Deeds, Sangeeta B Joshi, C Russell Middaugh, Christian Schöneich, David B Volkin, M Laird Forrest
Crofelemer is a botanical polymeric proanthocyanidin that inhibits chloride channel activity and is used clinically for treating HIV-associated secretory diarrhea. Crofelemer lots may exhibit significant physicochemical variation due to the natural source of the raw material. A variety of physical, chemical, and biological assays were used to identify potential critical quality attributes (CQAs) of crofelemer, which may be useful in characterizing differently sourced and processed drug products. Crofelemer drug substance was extracted from tablets of one commercial drug product lot, fractionated, and subjected to accelerated thermal degradation studies to produce derivative lots with variations in chemical and physical composition potentially representative of manufacturing and raw material variation...
July 22, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28691034/the-effects-of-time-lag-and-cure-rate-on-the-global-dynamics-of-hiv-1-model
#15
Nigar Ali, Gul Zaman, Abdullah, Aisha M Alqahtani, Ali Saleh Alshomrani
In this research article, a new mathematical model of delayed differential equations is developed which discusses the interaction among CD4 T cells, human immunodeficiency virus (HIV), and recombinant virus with cure rate. The model has two distributed intracellular delays. These delays denote the time needed for the infection of a cell. The dynamics of the model are completely described by the basic reproduction numbers represented by R0, R1, and R2. It is shown that if R0 < 1, then the infection-free equilibrium is locally as well as globally stable...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28685917/on-the-potential-of-a-short-term-intensive-intervention-to-interrupt-hcv-transmission-in-hiv-positive-men-who-have-sex-with-men-a-mathematical-modelling-study
#16
L Salazar-Vizcaya, R D Kouyos, J Fehr, D Braun, J Estill, E Bernasconi, J Delaloye, M Stöckle, P Schmid, M Rougemont, G Wandeler, H F Günthard, O Keiser, A Rauch
Increasing access to direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection and decelerating the rise in high-risk behaviour over the next decade could curb the HCV epidemic among HIV-positive men who have sex with men (MSM). We investigated if similar outcomes would be achieved by short-term intensive interventions like the Swiss-HCVree-trial. We used a HCV transmission model emulating two 12-months intensive interventions combining risk counselling with (i) universal DAA treatment (pangenotypic intervention) and (ii) DAA treatment for HCV genotypes 1 and 4 (replicating the Swiss-HCVree-trial)...
July 7, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28679753/on-the-death-rate-of-abortively-infected-cells-estimation-from-simian-human-immunodeficiency-virus-infection
#17
Ruian Ke, Mian-Er Cong, David Li, J Gerardo García-Lerma, Alan S Perelson
Progressive T cell depletion during chronic human immunodeficiency virus type 1 (HIV) infection is a key mechanism that leads to the development of AIDS. Recent studies have suggested that most T cells in the tissue die through pyroptosis triggered by abortive infection, i.e., infection of resting T cells in which HIV failed to complete reverse transcription. However, the contribution of abortive infection to T cell loss and how quickly abortively infected cells die in vivo, key parameters for a quantitative understanding of T cell population dynamics, are not clear...
September 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28678879/treatment-with-integrase-inhibitor-suggests-a-new-interpretation-of-hiv-rna-decay-curves-that-reveals-a-subset-of-cells-with-slow-integration
#18
E Fabian Cardozo, Adriana Andrade, John W Mellors, Daniel R Kuritzkes, Alan S Perelson, Ruy M Ribeiro
The kinetics of HIV-1 decay under treatment depends on the class of antiretrovirals used. Mathematical models are useful to interpret the different profiles, providing quantitative information about the kinetics of virus replication and the cell populations contributing to viral decay. We modeled proviral integration in short- and long-lived infected cells to compare viral kinetics under treatment with and without the integrase inhibitor raltegravir (RAL). We fitted the model to data obtained from participants treated with RAL-containing regimes or with a four-drug regimen of protease and reverse transcriptase inhibitors...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28659449/early-antiretroviral-therapy-and-potent-second-line-drugs-could-decrease-hiv-incidence-of-drug-resistance
#19
Mingwang Shen, Yanni Xiao, Libin Rong, Lauren Ancel Meyers, Steven E Bellan
Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing...
June 28, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28638104/anti-proliferative-therapy-for-hiv-cure-a-compound-interest-approach
#20
Daniel B Reeves, Elizabeth R Duke, Sean M Hughes, Martin Prlic, Florian Hladik, Joshua T Schiffer
In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4(+) T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size...
June 21, 2017: Scientific Reports
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