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HIV mathematical modeling

Mingwang Shen, Yanni Xiao, Libin Rong, Lauren Ancel Meyers, Steven E Bellan
BACKGROUND: Poor adherence to either antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) can promote drug resistance, though this risk is thought to be considerably higher for ART. In the population of men who have sex with men (MSM) in San Francisco, PrEP coverage reached 9.6% in 2014 and has continued to rise. Given the risk of drug resistance and high cost of second-line drugs, the costs and benefits of initiating ART earlier while expanding PrEP coverage remain unclear...
April 24, 2018: BMC Medicine
John M Murray
Objectives: The interaction between HIV and the immune system gives rise to a complex dynamical system. We therefore investigate whether delayed viral rebound after antiretroviral therapy (ART) interruption (ATI) may be due to an individual's viral-immune state being in a region of relative stability, and if so, how this can be extended. Methods: Using a mathematical model duplicating plasma viral levels, HIV DNA and immune homeostatic dynamics for individuals on ART commenced at either primary (PHI) or chronic (CHI) HIV infection, we investigate whether latent reservoir reductions and perturbations in other infected and uninfected memory CD4+ T cell subsets can delay viral rebound...
April 1, 2018: Journal of Virus Eradication
Simon de Montigny, Blythe J S Adamson, Benoît R Mâsse, Louis P Garrison, James G Kublin, Peter B Gilbert, Dobromir T Dimitrov
Promising multi-dose HIV vaccine regimens are being tested in trials in South Africa. We estimated the potential epidemiological and economic impact of HIV vaccine campaigns compared to continuous vaccination, assuming that vaccine efficacy is transient and dependent on immune response. We used a dynamic economic mathematical model of HIV transmission calibrated to 2012 epidemiological data to simulate vaccination with anticipated antiretroviral treatment scale-up in South Africa. We estimate that biennial vaccination with a 70% efficacious vaccine reaching 20% of the sexually active population could prevent 480,000-650,000 HIV infections (13...
April 17, 2018: Scientific Reports
Benjamin B Policicchio, Erwing Fabian Cardozo, Paola Sette, Cuiling Xu, George Haret-Richter, Tammy Dunsmore, Cristian Apetrei, Ivona Pandrea, Ruy M Ribeiro
CD8+ cells play a key role in HIV/SIV infection, but their specific mechanism(s) of action in controlling the virus are unclear. 2-LTR circles are extrachromosomal products generated upon failed integration of HIV/SIV. To understand the specific effects of CD8+ cells on infected cells, we analyzed the dynamics of 2-LTR circles in SIVmac251-infected rhesus macaques (RM) treated with an integrase inhibitor (INT). Twenty RMs underwent CD8+ cell depletion, received RAL monotherapy or a combination of both. Blood, lymph nodes (LNs) and gut biopsies were routinely sampled...
April 11, 2018: Journal of Virology
Ian H Spicknall, Katharine J Looker, Sami L Gottlieb, Harrell W Chesson, Joshua T Schiffer, Jocelyn Elmes, Marie-Claude Boily
Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would be a major step forward in improving global sexual and reproductive health. In this review, we identified published literature of dynamic mathematical models assessing the impact of either prophylactic or therapeutic HSV-2 vaccination at the population level. We compared each study's model structure and assumptions as well as predicted vaccination impact. We examined possible causes of heterogeneity across model predictions, key gaps, and the implications of these findings for future modelling efforts...
April 3, 2018: Vaccine
Kenneth A Freedberg, Nagalingeswaran Kumarasamy, Ethan D Borre, Eric L Ross, Kenneth H Mayer, Elena Losina, Soumya Swaminathan, Timothy P Flanigan, Rochelle P Walensky
Current Indian guidelines recommend twice-annual CD4 testing to monitor first-line antiretroviral therapy (ART), with a plasma HIV RNA test to confirm failure if CD4 declines, which would prompt a switch to second-line ART. We used a mathematical model to assess the clinical benefits and cost-effectiveness of alternative laboratory monitoring strategies in India. We simulated a cohort of HIV-infected patients initiating first-line ART and compared 11 strategies with combinations of CD4 and HIV RNA testing at varying frequencies...
March 12, 2018: AIDS Research and Human Retroviruses
Emmanuel Njeuhmeli, Marjorie Opuni, Melissa Schnure, Michel Tchuenche, Peter Stegman, Elizabeth Gold, Valerian Kiggundu, Nida Parks, Kim Seifert Ahanda, Maria Carrasco, Katharine Kripke
Background: The new World Health Organization and Joint United Nations Programme on HIV/AIDS strategic framework for voluntary medical male circumcision (VMMC) aims to increase VMMC coverage among males aged 10-29 years in priority settings to 90% by 2021. We use mathematical modeling to assess the likelihood that selected countries will achieve this objective, given their historical VMMC progress and current implementation options. Methods: We use the Decision Makers' Program Planning Toolkit, version 2, to examine 4 ambitious but feasible scenarios for scaling up VMMC coverage from 2017 through 2021, inclusive in Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Tanzania, Uganda, and Zimbabwe...
April 3, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ghina R Mumtaz, Susanne F Awad, Ali Feizzadeh, Helen A Weiss, Laith J Abu-Raddad
INTRODUCTION: Emerging HIV epidemics have been documented among people who inject drugs (PWID) in the Middle East and North Africa (MENA). This study estimates the HIV incidence among PWID due to sharing needles/syringes in MENA. It also delineates injecting drug use role as a driver of the epidemic in the population, and estimates impact of interventions. METHODS: A mathematical model of HIV transmission among PWID was applied in seven MENA countries with sufficient and recent epidemiological data and HIV prevalence ≥1% among PWID...
March 2018: Journal of the International AIDS Society
Nathan Geffen, Alex Welte
We review key mathematical models of the South African human immunodeficiency virus (HIV) epidemic from the early 1990s onwards. In our descriptions, we sometimes differentiate between the concepts of a model world and its mathematical or computational implementation. The model world is the conceptual realm in which we explicitly declare the rules - usually some simplification of 'real world' processes as we understand them. Computing details of informative scenarios in these model worlds is a task requiring specialist knowledge, but all other aspects of the modelling process, from describing the model world to identifying the scenarios and interpreting model outputs, should be understandable to anyone with an interest in the epidemic...
2018: Southern African Journal of HIV Medicine
Kanes Sucharitakul, Marie-Claude Boily, Dobromir Dimitrov, Kate M Mitchell
BACKGROUND: Many mathematical models have investigated the population-level impact of expanding antiretroviral therapy (ART), using different assumptions about HIV disease progression on ART and among ART dropouts. We evaluated the influence of these assumptions on model projections of the number of infections and deaths prevented by expanded ART. METHODS: A new dynamic model of HIV transmission among men who have sex with men (MSM) was developed, which incorporated each of four alternative assumptions about disease progression used in previous models: (A) ART slows disease progression; (B) ART halts disease progression; (C) ART reverses disease progression by increasing CD4 count; (D) ART reverses disease progression, but disease progresses rapidly once treatment is stopped...
2018: PloS One
Michael A Irvine, Bernhard P Konrad, Warren Michelow, Robert Balshaw, Mark Gilbert, Daniel Coombs
Increasing HIV testing rates among high-risk groups should lead to increased numbers of cases being detected. Coupled with effective treatment and behavioural change among individuals with detected infection, increased testing should also reduce onward incidence of HIV in the population. However, it can be difficult to predict the strengths of these effects and thus the overall impact of testing. We construct a mathematical model of an ongoing HIV epidemic in a population of gay, bisexual and other men who have sex with men...
March 2018: Journal of the Royal Society, Interface
Helen R Fryer, Steven M Wolinsky, Angela R McLean
Although antiretroviral drug therapy suppresses human immunodeficiency virus-type 1 (HIV-1) to undetectable levels in the blood of treated individuals, reservoirs of replication competent HIV-1 endure. Upon cessation of antiretroviral therapy, the reservoir usually allows outgrowth of virus and approaches to targeting the reservoir have had limited success. Ongoing cycles of viral replication in regions with low drug penetration contribute to this persistence. Here, we use a mathematical model to illustrate a new approach to eliminating the part of the reservoir attributable to persistent replication in drug sanctuaries...
March 2, 2018: PLoS Computational Biology
Sarah-Jane Anderson, Peter D Ghys, Regina Ombam, Timothy B Hallett
INTRODUCTION: Due to the nature of funding, national planners and international donors typically balance budgets over short time periods when designing HIV programmes (˜5-year funding cycles). We aim to explicitly quantify the cost of short-term funding arrangements on the success of future HIV prevention programmes. METHODS: Using mathematical models of HIV transmission in Kenya, we compare the impact of optimized combination prevention strategies under different constraints on investment over time...
March 2018: Journal of the International AIDS Society
Vitaly V Ganusov
The ability of human immunodeficiency virus (HIV) to avoid recognition by humoral and cellular immunity (viral escape) is well-documented, but the strength of the immune response needed to cause such a viral escape remains poorly quantified. Several previous studies observed a more rapid escape of HIV from CD8 T cell responses in the acute phase of infection compared to chronic infection. The rate of HIV escape was estimated with the help of simple mathematical models, and results were interpreted to suggest that CD8 T cell responses causing escape in acute HIV infection may be more efficient at killing virus-infected cells than responses that cause escape in chronic infection, or alternatively, that early escapes occur in epitopes mutations in which there is minimal fitness cost to the virus...
February 27, 2018: Viruses
Iulia A Neagu, Jason Olejarz, Mark Freeman, Daniel I S Rosenbloom, Martin A Nowak, Alison L Hill
Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus's life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus's susceptibility to the direct action of the drug...
February 2018: PLoS Computational Biology
Allison Perry, Parastu Kasaie, David W Dowdy, Maunank Shah
Background: The National HIV/AIDS Strategy has set ambitious goals to improve the epidemic in the United States. However, there is a paucity of usable program-level benchmarks tied to population-level epidemiologic goals. Our objective was to define tangible benchmarks for annual rates along the care continuum that are likely to translate to meaningful reductions in incidence. Methods: We used a validated mathematical model of HIV transmission and care engagement to characterize care continuum parameters that would translate into 50% reductions in incidence by 2025, compared with a base case scenario of the current US care continuum...
February 2018: Open Forum Infectious Diseases
Stefan Baral, Rachael M Turner, Carrie E Lyons, Sean Howell, Brian Honermann, Alex Garner, Robert Hess, Daouda Diouf, George Ayala, Patrick S Sullivan, Greg Millett
BACKGROUND: Gay, bisexual, and other cisgender men who have sex with men (GBMSM) are disproportionately affected by the HIV pandemic. Traditionally, GBMSM have been deemed less relevant in HIV epidemics in low- and middle-income settings where HIV epidemics are more generalized. This is due (in part) to how important population size estimates regarding the number of individuals who identify as GBMSM are to informing the development and monitoring of HIV prevention, treatment, and care programs and coverage...
February 8, 2018: JMIR Public Health and Surveillance
M Kumi Smith, Matthew Graham, Carl A Latkin, Vivian L Go
OBJECTIVES: Population mixing patterns can greatly inform allocation of HIV prevention interventions such as treatment as prevention (TasP) or preexposure prophyloaxis (PrEP). Characterizing contact patterns among subgroups can help identify the specific combinations of contact expected to result in the greatest number of new infections. SETTING: Baseline data from an intervention to reduce HIV related risk behaviors in male PWID the northern Vietnamese province of Thai Nguyen was used for the analysis...
January 30, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Javier Martinez-Picado, Ryan Zurakowski, María José Buzón, Mario Stevenson
Reverse transcription of HIV-1 results in the generation of a linear cDNA that serves as the precursor to the integrated provirus. Other classes of extrachromosomal viral cDNA molecules can be found in acutely infected cells including the 1-LTR and 2-LTR circles of viral DNA, also referred as episomal HIV-1 DNA. Circulating CD4+ T-cells of treatment-naïve individuals contain significant levels of unintegrated forms of HIV-1 DNA. However, the importance of episomal HIV-1 DNA in the study of viral persistence during antiviral therapy (ART) is debatable...
January 30, 2018: Retrovirology
Gui Liu, Monisha Sharma, Nicholas Tan, Ruanne V Barnabas
OBJECTIVE: HIV-positive women have higher human papillomavirus (HPV) prevalence and cervical cancer incidence than HIV-negative women, partly because of HIV's modifying effect on HPV pathogenesis. We synthesized the literature on the impact of HIV on HPV natural history. DESIGN: Systematic review and meta-analysis. METHODS: We searched the literature for studies evaluating HPV acquisition and persistence or precancer progression by HIV status...
March 27, 2018: AIDS
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