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HIV mathematical modeling

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https://www.readbyqxmd.com/read/28638104/anti-proliferative-therapy-for-hiv-cure-a-compound-interest-approach
#1
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
#2
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
#3
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...
June 1, 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
#4
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
#5
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
#6
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-workshop-synopsis
#7
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 May 5-6, 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 (ART) to HIV-infected infants diagnosed at birth...
June 5, 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
#8
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...
May 27, 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
#9
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...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28515014/hiv-and-the-criminalisation-of-drug-use-among-people-who-inject-drugs-a-systematic-review
#10
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
https://www.readbyqxmd.com/read/28514278/impact-of-screening-and-art-on-anal-cancer-incidence-in-hiv-positive-men-who-have-sex-with-men-mathematical-modeling-study
#11
Nello Blaser, Barbara Bertisch, Roger D Kouyos, Alexandra Calmy, Heiner C Bucher, Matthias Cavassini, Janne Estill, Olivia Keiser, Matthias Egger
BACKGROUND: The incidence of anal cancer is high in HIV-positive men who have sex with men (MSM). We modeled the impact of screening strategies and combination antiretroviral therapy (cART) coverage on anal cancer incidence in Switzerland. METHODS: Individual-based, dynamic simulation model parameterized with Swiss HIV Cohort Study (SHCS) and literature data. We assumed all men to be HPV infected. CD4 cell count trajectories were the main predictors of anal cancer...
May 16, 2017: AIDS
https://www.readbyqxmd.com/read/28514276/sexual-network-drivers-of-hiv-and-herpes-simplex-virus-type-2-hsv-2-transmission-a-comparative-mathematical-modeling-analysis
#12
Ryosuke Omori, Laith J Abu-Raddad
OBJECTIVES: HIV and herpes simplex virus type 2 (HSV-2) infections are sexually transmitted and propagate in sexual networks. Using mathematical modeling, we aimed to quantify effects of key network statistics on infection transmission, and extent to which HSV-2 prevalence can be a proxy of HIV prevalence. DESIGN/METHODS: An individual-based simulation model was constructed to describe sex partnering and infection transmission, and was parameterized with representative natural history, transmission, and sexual behavior data...
May 16, 2017: AIDS
https://www.readbyqxmd.com/read/28512685/modeling-brain-lentiviral-infections-during-antiretroviral-therapy-in-aids
#13
Weston C Roda, Michael Y Li, Michael S Akinwumi, Eugene L Asahchop, Benjamin B Gelman, Kenneth W Witwer, Christopher Power
Understanding HIV-1 replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was created to describe and predict the viral dynamics of HIV-1 and SIV infection within the brain during effective combination antiretroviral therapy (cART). The mathematical model was formulated based on the biology of lentiviral infection of brain macrophages and used to describe the dynamics of transmission and progression of lentiviral infection in brain...
May 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28505240/incidence-of-gonorrhea-and-chlamydia-following-hiv-preexposure-prophylaxis-among-men-who-have-sex-with-men-a-modeling-study
#14
Samuel M Jenness, Kevin M Weiss, Steven M Goodreau, Thomas Gift, Harrell Chesson, Karen W Hoover, Dawn K Smith, Albert Y Liu, Patrick S Sullivan, Eli S Rosenberg
Background: Preexposure prophylaxis (PrEP) is highly effective for preventing HIV, but risk compensation (RC) in men who have sex with men (MSM) raises concerns about increased sexually transmitted infections (STIs). CDC's PrEP guidelines recommend biannual STI screening, which may reduce incidence by treating STIs that would otherwise remain undiagnosed. We investigated the impact of these two potentially counteracting phenomena. Methods: With a stochastic network-based mathematical model of HIV and rectal/urogenital Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) transmission dynamics among MSM in the United States, we simulated PrEP uptake following the prescription indications and HIV/STI screening recommendations in the CDC guidelines...
May 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28493917/the-impact-of-hcv-therapy-in-a-high-hiv-hcv-prevalence-population-a-modeling-study-on-people-who-inject-drugs-in-ho-chi-minh-city-vietnam
#15
Ruthie B Birger, Thuy Le, Roger D Kouyos, Bryan T Grenfell, Timothy B Hallett
BACKGROUND: Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection is a major global health problem especially among people who inject drugs (PWID), with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV. METHODS: We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography...
2017: PloS One
https://www.readbyqxmd.com/read/28482004/imputing-direct-and-indirect-vaccine-effectiveness-of-childhood-pneumococcal-conjugate-vaccine-against-invasive-disease-by-surveying-temporal-changes-in-nasopharyngeal-pneumococcal-colonization
#16
Susan A Nzenze, Shabir A Madhi, Tinevimbo Shiri, Keith P Klugman, Linda de Gouveia, David P Moore, Alan S Karstaedt, Stefano Tempia, Marta C Nunes, Anne von Gottberg
The limited capabilities in most low-middle income countries to study the bebfit of pneumococcal conjugate vaccine (PCV) against invasive pneumococcal disease (IPD), calls for alternate strategies to assess this. We used a mathematical model, to predict the direct and indirect effectiveness of PCV by analyzing serotype specific colonization prevalence and IPD incidence prior to and following childhood PCV immunization in South Africa. We analyzed IPD incidence from 2005-2012 and colonization studies undertaken in HIV-uninfected and HIV-infected child-mother dyads from 2007-2009 (pre-PCV era), in 2010 (7-valent PCV era) and 2012 (13-valent PCV era)...
May 6, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28475648/hiv-1-competition-experiments-in-humanized-mice-show-that-apobec3h-imposes-selective-pressure-and-promotes-virus-adaptation
#17
Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S Harris, Yoshio Koyanagi, Kei Sato
APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo...
May 5, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28472928/using-the-multiphase-optimization-strategy-most-to-optimize-an-hiv-care-continuum-intervention-for-vulnerable-populations-a-study-protocol
#18
Marya Viorst Gwadz, Linda M Collins, Charles M Cleland, Noelle R Leonard, Leo Wilton, Monica Gandhi, R Scott Braithwaite, David C Perlman, Alexandra Kutnick, Amanda S Ritchie
BACKGROUND: More than half of persons living with HIV (PLWH) in the United States are insufficiently engaged in HIV primary care and not taking antiretroviral therapy (ART), mainly African Americans/Blacks and Hispanics. In the proposed project, a potent and innovative research methodology, the multiphase optimization strategy (MOST), will be employed to develop a highly efficacious, efficient, scalable, and cost-effective intervention to increase engagement along the HIV care continuum...
May 4, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28472445/defining-the-population-attributable-fraction-for-infectious-diseases
#19
Ellen Brooks-Pollock, Leon Danon
Background: The population attributable fraction (PAF) is used to quantify the contribution of a risk group to disease burden. For infectious diseases, high-risk individuals may increase disease risk for the wider population in addition to themselves; therefore methods are required to estimate the PAF for infectious diseases. Methods: A mathematical model of disease transmission in a population with a high-risk group was used to compare existing approaches for calculating the PAF...
May 4, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28472201/predicting-hiv-1-transmission-and-antibody-neutralization-efficacy-in-vivo-from-stoichiometric-parameters
#20
Oliver F Brandenberg, Carsten Magnus, Peter Rusert, Huldrych F Günthard, Roland R Regoes, Alexandra Trkola
The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization...
May 2017: PLoS Pathogens
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