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HIV mathematical modeling

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https://www.readbyqxmd.com/read/28807188/the-global-burden-of-tuberculosis-mortality-in-children-a-mathematical-modelling-study
#1
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
#2
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
#3
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
#4
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
#5
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 utilized to identify potential critical quality attributes (CQAs) of crofelemer, which may be useful in characterizing differently sourced and/or processed drug products. Crofelemer drug substance was extracted from tablets of one commerical 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
#6
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
#7
Luisa Salazar-Vizcaya, Roger D Kouyos, Jan Fehr, Dominique Braun, Janne Estill, Enos Bernasconi, Julie Delaloye, Marcel Stöckle, Patrick Schmid, Mathieu Rougemont, Gilles Wandeler, Huldrych F Günthard, Olivia Keiser, Andri 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 1) universal DAA-treatment (pangenotypic intervention) and 2) 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
#8
Ruian Ke, Mian-Er Cong, David Li, Gerardo Garcia-Lerma, Alan S Perelson
Progressive T cell depletion during chronic human immunodeficiency virus (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 where 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...
July 5, 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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28630490/pyroptosis-superinfection-and-the-maintenance-of-the-latent-reservoir-in-hiv-1-infection
#12
Dominik Wodarz, David N Levy
A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627929/design-of-the-hptn-065-tlc-plus-study-a-study-to-evaluate-the-feasibility-of-an-enhanced-test-link-to-care-plus-treat-approach-for-hiv-prevention-in-the-united-states
#13
Theresa Gamble, Bernard Branson, Deborah Donnell, H Irene Hall, Georgette King, Blayne Cutler, Shannon Hader, David Burns, Jason Leider, Angela Fulwood Wood, Kevin G Volpp, Kate Buchacz, Wafaa M El-Sadr
Background/Aims HIV continues to be a major public health threat in the United States, and mathematical modeling has demonstrated that the universal effective use of antiretroviral therapy among all HIV-positive individuals (i.e. the "test and treat" approach) has the potential to control HIV. However, to accomplish this, all the steps that define the HIV care continuum must be achieved at high levels, including HIV testing and diagnosis, linkage to and retention in clinical care, antiretroviral medication initiation, and adherence to achieve and maintain viral suppression...
August 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28617810/population-level-impact-of-an-accelerated-hiv-response-plan-to-reach-the-unaids-90-90-90-target-in-c%C3%A3-te-d-ivoire-insights-from-mathematical-modeling
#14
Mathieu Maheu-Giroux, Juan F Vesga, Souleymane Diabaté, Michel Alary, Stefan Baral, Daouda Diouf, Kouamé Abo, Marie-Claude Boily
BACKGROUND: National responses will need to be markedly accelerated to achieve the ambitious target of the Joint United Nations Programme on HIV/AIDS (UNAIDS). This target aims for 90% of HIV-positive individuals to be aware of their status, for 90% of those aware to receive antiretroviral therapy (ART), and for 90% of those on treatment to have a suppressed viral load by 2020, with each individual target reaching 95% by 2030. We aimed to estimate the impact of various treatment-as-prevention scenarios in Côte d'Ivoire, one of the countries with the highest HIV incidence in West Africa, with unmet HIV prevention and treatment needs, and where key populations are important to the broader HIV epidemic...
June 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28605504/projecting-10-yr-20-yr-and-lifetime-risks-of-cardiovascular-disease-in-persons-living-with-hiv-in-the-us
#15
E Losina, E P Hyle, E D Borre, B P Linas, P E Sax, M C Weinstein, C Rusu, A L Ciaranello, R P Walensky, K A Freedberg
Background: Cardiovascular disease (CVD) is an increasing cause of morbidity among persons living with HIV (PLWH). We projected cumulative CVD risk in PLWH in care compared to the US general population and persons HIV-uninfected, but at high risk for HIV. Methods: We used a mathematical model to project cumulative CVD incidence. We simulated a male and female cohort for each of three populations: 1) US general population; 2) HIV-uninfected, at high risk for HIV; and 3) PLWH...
June 12, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28605503/behavioural-not-biological-factors-drive-the-hcv-epidemic-among-hiv-positive-msm-hcv-and-hiv-modelling-analysis-including-hcv-treatment-as-prevention-impact
#16
Louis MacGregor, Natasha K Martin, Christinah Mukandavire, Ford Hickson, Peter Weatherburn, Matthew Hickman, Peter Vickerman
Background: Uncertainty surrounds why hepatitis C virus (HCV) is concentrated among HIV-positive men who have sex with men (MSM). We used mathematical modelling to explore reasons for these infection patterns, and implications for HCV treatment-as-prevention. Methods: Using a joint MSM HIV/HCV transmission model parameterized with UK behavioural data, we considered how biological (heightened HCV infectivity and reduced spontaneous clearance among HIV-positive MSM) and/or behavioural factors (preferential sexual mixing by HIV status and risk heterogeneity) could concentrate HCV infection in HIV-positive MSM as commonly observed (5-20 times the HCV prevalence in HIV-negative MSM; defined as the HCV ratio)...
June 12, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28590330/hiv-birth-testing-and-linkage-to-care-for-hiv-infected-infants
#17
Patrick Jean-Philippe, Hans Spiegel, Devasena Gnanashanmugam, Joseph Fitzgibbon, Patricia DʼSouza, Keith W Crawford, Lakshmi Jayashankar, Melanie C Bacon, Shaffiq M Essajee, Grace M Aldrovandi, Mark Cotton, Elaine J Abrams
: On 5-6 May 2016, the division of AIDS of the National Institute of Allergy and Infectious Diseases convened a workshop on 'HIV Birth Testing and Linkage to Care for HIV Infected Infants.' The goal of the workshop was to evaluate birth testing for early infant diagnosis (EID) of HIV, delineate technological resources for advancing a point-of-care (POC) HIV test implementable at birth and chart out the implementation hurdles for initiating early antiretroviral therapy to HIV-infected infants diagnosed at birth...
August 24, 2017: AIDS
https://www.readbyqxmd.com/read/28556627/a-mathematical-model-to-predict-hiv-virological-failure-and-elucidate-the-role-of-lymph-node-drug-penetration
#18
S Sanche, N Sheehan, T Mesplède, M A Wainberg, J Li, F Nekka
Preventing virological failure following HIV treatment remains a difficult task that is further complicated by the emergence of drug resistance. We have developed a mathematical model able to explain and predict HIV virological outcomes for various compounds and patients' drug intake patterns. Compared to current approaches, this model considers, altogether, drug penetration into lymph nodes, a refined adherence representation accounting for the propensity for long drug holidays, population pharmacokinetic and pharmacodynamic variability, drug interaction, and crossresistance...
July 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28534885/modeling-combination-hcv-prevention-among-hiv-infected-men-who-have-sex-with-men-and-people-who-inject-drugs
#19
Natasha K Martin, Britt Skaathun, Peter Vickerman, David Stuart
People who inject drugs (PWID) and HIV-infected men who have sex with men (MSM) are key risk groups for HCV transmission. Mathematical modeling studies can help elucidate what level and combination of prevention intervention scale-up is required to control or eliminate epidemics among these key populations. We discuss the evidence surrounding HCV prevention interventions and provide an overview of the mathematical modeling literature projecting the impact of scaled-up HCV prevention among PWID and HIV-infected MSM...
April 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28515014/hiv-and-the-criminalisation-of-drug-use-among-people-who-inject-drugs-a-systematic-review
#20
Kora DeBeck, Tessa Cheng, Julio S Montaner, Chris Beyrer, Richard Elliott, Susan Sherman, Evan Wood, Stefan Baral
BACKGROUND: Mounting evidence suggests that laws and policies prohibiting illegal drug use could have a central role in shaping health outcomes among people who inject drugs (PWID). To date, no systematic review has characterised the influence of laws and legal frameworks prohibiting drug use on HIV prevention and treatment. METHODS: Consistent with PRISMA guidelines, we did a systematic review of peer-reviewed scientific evidence describing the association between criminalisation of drug use and HIV prevention and treatment-related outcomes among PWID...
May 12, 2017: Lancet HIV
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