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HIV mathematical modeling

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https://www.readbyqxmd.com/read/29232366/estimating-the-impact-of-antiretroviral-treatment-on-adult-mortality-trends-in-south-africa-a-mathematical-modelling-study
#1
Leigh F Johnson, Margaret T May, Rob E Dorrington, Morna Cornell, Andrew Boulle, Matthias Egger, Mary-Ann Davies
BACKGROUND: Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART. METHODS AND FINDINGS: Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration...
December 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29223580/modeling-hiv-disease-progression-and-transmission-at-population-level-the-potential-impact-of-modifying-disease-progression-in-hiv-treatment-programs
#2
Jennifer M Ross, Roger Ying, Connie L Celum, Jared M Baeten, Katherine K Thomas, Pamela M Murnane, Heidi van Rooyen, James P Hughes, Ruanne V Barnabas
INTRODUCTION: Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated...
December 5, 2017: Epidemics
https://www.readbyqxmd.com/read/29220115/hiv-prevention-where-it-is-needed-most-comparison-of-strategies-for-the-geographical-allocation-of-interventions
#3
Sarah-Jane Anderson, Peter D Ghys, Regina Ombam, Timothy B Hallett
INTRODUCTION: A strategic approach to the application of HIV prevention interventions is a core component of the UNAIDS Fast Track strategy to end the HIV epidemic by 2030. Central to these plans is a focus on high-prevalence geographies, in a bid to target resources to those in greatest need and maximize the reduction in new infections. Whilst this idea of geographical prioritization has the potential to improve efficiency, it is unclear how it should be implemented in practice. There are a range of prevention interventions which can be applied differentially across risk groups and locations, making allocation decisions complex...
December 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29182894/evaluating-the-evidence-for-more-frequent-than-annual-hiv-screening-of-gay-bisexual-and-other-men-who-have-sex-with-men-in-the-united-states-results-from-a-systematic-review-and-cdc-expert-consultation
#4
Elizabeth A DiNenno, Joseph Prejean, Kevin P Delaney, Kristina Bowles, Tricia Martin, Amrita Tailor, Gema Dumitru, Mary M Mullins, Angela Hutchinson, Amy Lansky
The Centers for Disease Control and Prevention (CDC) recommended in 2006 that sexually active gay, bisexual, and other men who have sex with men (MSM) be screened for human immunodeficiency virus (HIV) at least annually. A workgroup comprising CDC and external experts conducted a systematic review of the literature, including benefits, harms, acceptability, and feasibility of annual versus more frequent screening among MSM, to determine whether evidence was sufficient to change the current recommendation. Four consultations with managers of public and nonprofit HIV testing programs, clinics, and mathematical modeling experts were conducted to provide input on the programmatic and scientific evidence...
January 1, 2017: Public Health Reports
https://www.readbyqxmd.com/read/29171179/optimal-timing-of-viral-load-monitoring-during-pregnancy-to-predict-viraemia-at-delivery-in-hiv-infected-women-initiating-art-in-south-africa-a-simulation-study
#5
Maia Lesosky, Tracy Glass, Elton Mukonda, Nei-Yuan Hsiao, Elaine J Abrams, Landon Myer
INTRODUCTION: HIV viral load (VL) monitoring is a central tool to evaluate ART effectiveness and transmission risk. There is a global movement to expand VL monitoring following recent recommendations from the World Health Organization (WHO), but there has been little research into VL monitoring in pregnant women. We investigated one important question in this area: when and how frequently VL should be monitored in women initiating ART during pregnancy to predict VL at the time of delivery in a simulated South African population...
November 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29164341/mathematical-models-of-hiv-latency
#6
Alison L Hill
Viral latency is a major barrier to curing HIV infection with antiretroviral therapy, and consequently, for eliminating the disease globally. The establishment, maintenance, and potential clearance of latent infection are complex dynamic processes and can be best understood and described with the help of mathematical models. Here we review the use of viral dynamics models for HIV, with a focus on applications to the latent reservoir. Such models have been used to explain the multiphasic decay of viral load during antiretroviral therapy, the early seeding of the latent reservoir during acute infection and the limited inflow during treatment, the dynamics of viral blips, and the phenomenon of posttreatment control...
November 22, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29161835/three-level-global-resource-allocation-model-for-hiv-control-a-hierarchical-decision-system-approach
#7
Semu Mitiku Kassa
Funds from various global organizations, such as, The Global Fund, The World Bank, etc. are not directly distributed to the targeted risk groups. Especially in the so-called third-world-countries, the major part of the fund in HIV prevention programs comes from these global funding organizations. The allocations of these funds usually pass through several levels of decision making bodies that have their own specific parameters to control and specific objectives to achieve. However, these decisions are made mostly in a heuristic manner and this may lead to a non-optimal allocation of the scarce resources...
February 1, 2018: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/29161831/an-exact-approach-to-calibrating-infectious-disease-models-to-surveillance-data-the-case-of-hiv-and-hsv-2
#8
David J Gerberry
When mathematical models of infectious diseases are used to inform health policy, an important first step is often to calibrate a model to disease surveillance data for a specific setting (or multiple settings). It is increasingly common to also perform sensitivity analyses to demonstrate the robustness, or lack thereof, of the modeling results. Doing so requires the modeler to find multiple parameter sets for which the model produces behavior that is consistent with the surveillance data. While frequently overlooked, the calibration process is nontrivial at best and can be inefficient, poorly communicated and a major hurdle to the overall reproducibility of modeling results...
February 1, 2018: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/29135576/assisted-partner-notification-services-are-cost-effective-for-decreasing-hiv-burden-in-western-kenya-a-mathematical-modeling-analysis
#9
Monisha Sharma, Jennifer A Smith, Carey Farquhar, Roger Ying, Peter Cherutich, Matthew Golden, Beatrice Wamuti, David Bukusi, Hans Spiegel, Ruanne V Barnabas
BACKGROUND: Assisted partner services (aPS) or provider notification for sexual partners of persons diagnosed HIV-positive can increase HIV testing and linkage in sub-Saharan Africa (SSA) and is a high yield strategy to identify HIV-positive persons. However, its cost-effectiveness is not well-evaluated. METHODS: Using effectiveness and cost data from an aPS trial in Kenya, we parameterized an individual-based, dynamic HIV transmission model. We estimated costs for both a program scenario and a task-shifting scenario using community health workers to conduct the intervention...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29129712/estimating-the-annual-risk-of-hiv-transmission-within-hiv-sero-discordant-couples-in-sub-saharan-africa
#10
Susanne F Awad, Hiam Chemaitelly, Laith J Abu-Raddad
OBJECTIVE: To estimate the annual risk of HIV transmission (ϕ) within HIV sero-discordant couples in 23 countries in sub-Saharan Africa (SSA), by utilizing newly-available national population-based data and accounting for factors known to potentially affect this estimation. METHODS: We used a recently-developed pair-based mathematical model that accommodates for HIV-dynamics temporal variation, sexual risk-behavior heterogeneity, and antiretroviral therapy (ART) scale-up...
November 9, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29118123/estimating-initial-viral-levels-during-hiv-siv-reactivation-from-latency
#11
Mykola Pinkevych, Christine M Fennessey, Deborah Cromer, Martin Tolstrup, Ole S Søgaard, Thomas A Rasmussen, Brandon F Keele, Miles P Davenport
HIV viremia rebounds rapidly after treatment interruption, and a variety of strategies are being explored to reduce or control viral reactivation post-treatment. This viral rebound arises from reactivation of individual latently infected cells, which spread during ongoing rounds of productive infection. The level of virus produced by the initial individual reactivating cells is not known, although it may have major implications for the ability of different immune interventions to control viral rebound. Here we use data from both HIV and SIV treatment interruption studies to estimate the initial viral load post-interruption and thereby the initial individual reactivation event...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29112956/hiv-1-persistence-following-extremely-early-initiation-of-antiretroviral-therapy-art-during-acute-hiv-1-infection-an-observational-study
#12
Timothy J Henrich, Hiroyu Hatano, Oliver Bacon, Louise E Hogan, Rachel Rutishauser, Alison Hill, Mary F Kearney, Elizabeth M Anderson, Susan P Buchbinder, Stephanie E Cohen, Mohamed Abdel-Mohsen, Christopher W Pohlmeyer, Remi Fromentin, Rebecca Hoh, Albert Y Liu, Joseph M McCune, Jonathan Spindler, Kelly Metcalf-Pate, Kristen S Hobbs, Cassandra Thanh, Erica A Gibson, Daniel R Kuritzkes, Robert F Siliciano, Richard W Price, Douglas D Richman, Nicolas Chomont, Janet D Siliciano, John W Mellors, Steven A Yukl, Joel N Blankson, Teri Liegler, Steven G Deeks
BACKGROUND: It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29112075/consequences-of-a-changing-us-strategy-in-the-global-hiv-investment-landscape
#13
Jessica B McGillen, Alana Sharp, Brian Honermann, Gregorio Millett, Chris Collins, Timothy B Hallett
OBJECTIVE: The global fight against HIV/AIDS in Africa has long been a focus of US foreign policy, but this could change if the federal budget for 2018 proposed by the US Office of Management and Budget is adopted. We aim to inform public and Congressional debate around this issue by evaluating the historical and potential future impact of US investment in the African HIV response. DESIGN/METHODS: We use a previously published mathematical model of HIV transmission to characterize the possible impact of a series of financial scenarios for the historical and future AIDS response across Sub-Saharan Africa...
November 28, 2017: AIDS
https://www.readbyqxmd.com/read/29099920/achieving-90-90-90-hiv-targets-will-not-be-enough-to-achieve-the-hiv-incidence-reduction-target-in-australia
#14
Nick Scott, Mark Stoové, Sherrie L Kelly, David P Wilson, Margaret E Hellard
Background: We estimated the HIV incidence reduction in Australia corresponding to achieving the UNAIDS 90-90-90 targets by 2020 and extended targets of 95-95-95 by 2030, in combination with various scale-ups of HIV testing, primary prevention and pre-exposure prophylaxis (PrEP) among high-risk men who have sex with men (MSM). These projections were evaluated against the target of achieving a 90% reduction in HIV incidence by 2030 compared with 2010 levels. Methods: A mathematical model was used to project annual HIV incidence for combinations of HIV care cascade targets, testing frequencies, primary prevention coverages and levels of PrEP scale-up...
November 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29068470/aspartate-%C3%AE-semialdeyhyde-dehydrogenase-as-a-potential-therapeutic-target-of-mycobacterium-tuberculosis-h37rv-evidence-from-in-silico-elementary-mode-analysis-of-biological-network-model
#15
Saif Khan, Pallavi Somvanshi, Tulika Bhardwaj, Raju K Mandal, Sajad A Dar, Mohd Wahid, Arshad Jawed, Mohtashim Lohani, Mahvish Khan, Mohammed Y Areeshi, Shafiul Haque
The emergence of multi-drug resistant strains and co-occurrence of tuberculosis with HIV creates a major burden to the human health globally. Failure of primary antibacterial therapy necessitates the identification of new mycobacterial drugs. In this study, a comprehensive analysis involving bottom-up systems biology approach was applied wherein we have identified potential therapeutic targets of Mycobacterium tuberculosis infections. Our study prioritized M. tuberculosis therapeutic targets [aspartate-β-semialdeyhde dehydrogenase (ASD), dihydrodipicolinate reductase and diaminopimelate decarboxylase] based on flux and elementary mode analysis using direct mathematical modeling of the relevant metabolic pathways...
October 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29055819/dynamics-of-lentiviral-infection-in-vivo-in-the-absence-of-adaptive-immune-responses
#16
Elissa J Schwartz, Naveen K Vaidya, Karin S Dorman, Susan Carpenter, Robert H Mealey
Understanding the dynamics of acute viral infection is crucial for developing strategies to prevent and control infection. In this study, lentiviral dynamics in a host without adaptive immunity were examined in order to determine kinetic parameters of infection and quantify the effect of neutralizing antibodies in preventing infection, using mathematical modeling of data from equine infectious anemia virus (EIAV) infection of horses with severe combined immunodeficiency (SCID). Estimated parameters were used to calculate the basic reproductive number and virus doubling time and found that the rate that antibodies neutralized virus was ~18 times greater than the virus clearance rate...
October 19, 2017: Virology
https://www.readbyqxmd.com/read/29049331/hiv-dynamics-linked-to-memory-cd4-t-cell-homeostasis
#17
John M Murray, John Zaunders, Sean Emery, David A Cooper, William J Hey-Nguyen, Kersten K Koelsch, Anthony D Kelleher
The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART). We investigated whether plasma viral level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest changes over the 1st year of ART...
2017: PloS One
https://www.readbyqxmd.com/read/29045398/nonlatching-positive-feedback-enables-robust-bimodality-by-decoupling-expression-noise-from-the-mean
#18
Brandon S Razooky, Youfang Cao, Maike M K Hansen, Alan S Perelson, Michael L Simpson, Leor S Weinberger
Fundamental to biological decision-making is the ability to generate bimodal expression patterns where 2 alternate expression states simultaneously exist. Here, we use a combination of single-cell analysis and mathematical modeling to examine the sources of bimodality in the transcriptional program controlling HIV's fate decision between active replication and viral latency. We find that the HIV transactivator of transcription (Tat) protein manipulates the intrinsic toggling of HIV's promoter, the long terminal repeat (LTR), to generate bimodal ON-OFF expression and that transcriptional positive feedback from Tat shifts and expands the regime of LTR bimodality...
October 2017: PLoS Biology
https://www.readbyqxmd.com/read/28980928/optimizing-expression-of-antiviral-cyanovirin-n-homology-gene-using-response-surface-methodology-and-protein-structure-prediction
#19
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
#20
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
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