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HIV mathematical modeling

Catherine Hankins, Mitchell Warren, Emmanuel Njeuhmeli
Over 11 million voluntary medical male circumcisions (VMMC) have been performed of the projected 20.3 million needed to reach 80% adult male circumcision prevalence in priority sub-Saharan African countries. Striking numbers of adolescent males, outside the 15-49-year-old age target, have been accessing VMMC services. What are the implications of overall progress in scale-up to date? Can mathematical modeling provide further insights on how to efficiently reach the male circumcision coverage levels needed to create and sustain further reductions in HIV incidence to make AIDS no longer a public health threat by 2030? Considering ease of implementation and cultural acceptability, decision makers may also value the estimates that mathematical models can generate of immediacy of impact, cost-effectiveness, and magnitude of impact resulting from different policy choices...
2016: PloS One
Amber Kunkel, Forrest W Crawford, James Shepherd, Ted Cohen
OBJECTIVE: Extending the duration of isoniazid preventive therapy (IPT) among people living with HIV (PLHIV) may improve its effectiveness at both individual and population levels, but could also increase selective pressure in favor of isoniazid-resistant tuberculosis (TB) strains. The objective of this study was to determine the relative importance of these two effects. METHODS: Transmission dynamic model. DESIGN: We created a mathematical model of TB transmission incorporating HIV incidence and treatment, mixed strain latent TB infections, and four different phenotypes of TB drug resistance (pan-susceptible, isoniazid monoresistant, rifampicin monoresistant, and multidrug resistant)...
November 13, 2016: AIDS
Jack J Olney, Paula Braitstein, Jeffrey W Eaton, Edwin Sang, Monicah Nyambura, Sylvester Kimaiyo, Ellen McRobie, Joseph W Hogan, Timothy B Hallett
BACKGROUND: With expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health. METHODS: We created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya...
October 19, 2016: Lancet HIV
Matthew L Paff, Scott L Nuismer, Andrew D Ellington, Ian J Molineux, Ryan H May, James J Bull
BACKGROUND: We propose, model, and implement a novel system of population-level intervention against a virus. One context is a treatment against a chronic infection such as HIV. The underlying principle is a form of virus 'wars' in which a benign, transmissible agent is engineered to protect against infection by and spread of a lethal virus. In our specific case, the protective agent consists of two entities, a benign virus and a gene therapy vector mobilized by the benign virus. RESULTS: Numerical analysis of a mathematical model identified parameter ranges in which adequate, population-wide protection is achieved...
2016: Journal of Biological Engineering
Boopathy Ramakrishnan, Karthik Viswanathan, Kannan Tharakaraman, Vlado Dančík, Rahul Raman, Gregory J Babcock, Zachary Shriver, Ram Sasisekharan
Broadly neutralizing monoclonal antibodies (bNAbs) for viral infections, such as HIV, respiratory syncytial virus (RSV), and influenza, are increasingly entering clinical development. For influenza, most neutralizing antibodies target influenza virus hemagglutinin. These bNAbs represent an emerging, promising modality for treatment and prophylaxis of influenza due to their multiple mechanisms of antiviral action and generally safe profile. Preclinical work in other viral diseases, such as dengue, has demonstrated the potential for antibody-based therapies to enhance viral uptake, leading to enhanced viremia and worsening of disease...
October 14, 2016: Trends in Microbiology
Xia Wang, Sanyi Tang, Xinyu Song, Libin Rong
HIV can infect cells via virus-to-cell infection or cell-to-cell viral transmission. These two infection modes may occur in a synergistic way and facilitate viral spread within an infected individual. In this paper, we developed an HIV latent infection model including both modes of transmission and time delays between viral entry and integration or viral production. We analysed the model by defining the basic reproductive number, showing the existence, positivity and boundedness of the solution, and proving the local and global stability of the infection-free and infected steady states...
October 12, 2016: Journal of Biological Dynamics
Till Bärnighausen, David E Bloom, Salal Humair
Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART's prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it...
2016: PloS One
K F Gurski, K A Hoffman
In 1992, Watts and May introduced a simple dynamical systems model of the spread of HIV based on disease transmission per partnership including the length of partnership duration. This model allowed for the treatment of concurrent partnerships, although it was hampered by the assumption of an important latent phase which generated a non-autonomous system. Subsequent models including concurrency have been based on networks, Monte Carlo, and stochastic simulations which lose a qualitative understanding of the effects of concurrency...
October 3, 2016: Mathematical Biosciences
Katrina A Lythgoe, François Blanquart, Lorenzo Pellis, Christophe Fraser
The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models...
October 2016: PLoS Biology
Yuqin Zhao, Daniel T Wood, Hristo V Kojouharov, Yang Kuang, Dobromir T Dimitrov
Mechanistic mathematical models are increasingly used to evaluate the effectiveness of different interventions for HIV prevention and to inform public health decisions. By focusing exclusively on the impact of the interventions, the importance of the demographic processes in these studies is often underestimated. In this paper, we use simple deterministic models to assess the effectiveness of pre-exposure prophylaxis in reducing the HIV transmission and to explore the influence of the recruitment mechanisms on the epidemic and effectiveness projections...
October 4, 2016: Bulletin of Mathematical Biology
Robert L Glaubius, Urvi M Parikh, Greg Hood, Kerri J Penrose, Eran Bendavid, John W Mellors, Ume L Abbas
Background.  A long-acting injectable formulation of rilpivirine (RPV), under investigation as antiretroviral pre-exposure prophylaxis (PrEP), may facilitate PrEP adherence. In contrast, cross-resistance between RPV and nonnucleoside reverse-transcriptase inhibitors comprising first-line antiretroviral therapy (ART) could promote human immunodeficiency virus (HIV) drug resistance and reduce PrEP's effectiveness. Methods.  We use novel mathematical modeling of different RPV PrEP scale-up strategies in KwaZulu-Natal, South Africa, to investigate their effects on HIV prevention and drug resistance, compared with a reference scenario without PrEP...
September 2016: Open Forum Infectious Diseases
N J Malunguza, S D Hove-Musekwa, S Dube, Z Mukandavire
Super-infection by multiple HIV-1 subtypes, previously thought restricted to high risk groups, has now been reported in the general heterosexual populations at relatively the same incidence rate as in high risk groups. We present a simple deterministic HIV model with super-infection by two HIV-1 subtypes. Mathematical characteristics including the basic reproductive number [Formula: see text], invasion threshold [Formula: see text] and conditions for asymptotic stability are derived. In the absence of super-infection the model exhibits competitive exclusion, and all equilibria are globally attracting if they exist except for the disease free which is a saddle for [Formula: see text] The results show that the subtype with the dominant reproductive number exceeding unity dominates the weaker subtype forcing it to extinction regardless of the size of the reproductive number...
September 25, 2016: Mathematical Medicine and Biology: a Journal of the IMA
Naveen K Vaidya, Ruy M Ribeiro, Alan S Perelson, Anil Kumar
Complications of HIV-1 infection in individuals who utilize drugs of abuse is a significant problem, because these drugs have been associated with higher virus replication and accelerated disease progression as well as severe neuropathogenesis. To gain further insight it is important to quantify the effects of drugs of abuse on HIV-1 infection dynamics. Here, we develop a mathematical model that incorporates experimentally observed effects of morphine on inducing HIV-1 co-receptor expression. For comparison we also considered viral dynamic models with cytolytic or noncytolytic effector cell responses...
September 2016: PLoS Computational Biology
Brooke E Nichols, Charles A B Boucher, Marc van der Valk, Bart J A Rijnders, David A M C van de Vijver
BACKGROUND: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation. METHODS: We developed a deterministic mathematical model, calibrated to the well defined Dutch HIV epidemic among MSM, to predict the effect and cost-effectiveness of PrEP...
September 22, 2016: Lancet Infectious Diseases
Timokratis Karamitros, Dimitrios Paraskevis, Angelos Hatzakis, Mina Psichogiou, Ioannis Elefsiniotis, Tara Hurst, Anna-Maria Geretti, Apostolos Beloukas, John Frater, Paul Klenerman, Aris Katzourakis, Gkikas Magiorkinis
Endogenous retroviruses (ERVs) comprise 6-8% of the human genome. HERVs are silenced in most normal tissues, up-regulated in stem cells and in placenta but also in cancer and HIV-1 infection. Crucially, there are conflicting reports on detecting HERV RNA in non-cellular clinical samples such as plasma that suggest the study of HERV RNA can be daunting. Indeed, we find that the use of real-time PCR in a quality assured clinical laboratory setting can be sensitive to low-level proviral contamination. We developed a mathematical model for low-level contamination that allowed us to design a laboratory protocol and standard operating procedures for robust measurement of HERV RNA...
2016: Scientific Reports
Annick Bórquez, Anne Cori, Erica L Pufall, Jingo Kasule, Emma Slaymaker, Alison Price, Jocelyn Elmes, Basia Zaba, Amelia C Crampin, Joseph Kagaayi, Tom Lutalo, Mark Urassa, Simon Gregson, Timothy B Hallett
BACKGROUND: Programmatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates. METHODS AND FINDINGS: We developed a predictive model, the Incidence Patterns Model (IPM), representing populations according to factors that have been demonstrated to be strongly associated with HIV acquisition risk: gender, marital/sexual activity status, geographic location, "key populations" based on risk behaviours (sex work, injecting drug use, and male-to-male sex), HIV and ART status within married or cohabiting unions, and circumcision status...
September 2016: PLoS Medicine
Kate M Mitchell, Holly J Prudden, Reynold Washington, Shajy Isac, Subramanian P Rajaram, Anna M Foss, Fern Terris-Prestholt, Marie-Claude Boily, Peter Vickerman
INTRODUCTION: In Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre-exposure prophylaxis (PrEP) has high anti-HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers. We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore. METHODS: A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low-risk groups was parameterized and fitted to Bangalore data...
2016: Journal of the International AIDS Society
Xinrui Wu, Qianru Dou, Yugang Bao, Yanhui Zhang, Hongzhuan Tan
OBJECTIVE: To analyze the sexual behavior characteristics of the sexually transmitted HIV-positive people and to estimate the secondary transmission rate.
 METHODS: Field investigation and literature review were conducted among sexually transmitted HIV-positive people to collect general information during the last 6 months before notification of HIV infection. A mathematical model was used to estimate the secondary transmission rate.
 RESULTS: A total of 769 HIV-positive people were recruited for the study, 186 of them were women, 286 were men who have sex with women (MSW), 242 were men who have sex with men (MSM) and 55 were men who have sex with men and women (MSMW)...
July 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Jessica B McGillen, Sarah-Jane Anderson, Mark R Dybul, Timothy B Hallett
BACKGROUND: Advances in HIV prevention methods offer promise to accelerate declines in incidence, but how these methods can be deployed to have the best effect on the heterogeneous landscape and drivers of the pandemic remains unclear. We postulated that use of epidemic heterogeneity to inform the allocation of resources for combination HIV prevention could enhance the impact of HIV funding across sub-Saharan Africa. METHODS: We developed a compartmental mathematical model of HIV transmission and disease progression by risk group to subnational resolution in 18 countries, capturing 80% of the adult HIV burden in sub-Saharan Africa...
September 2016: Lancet HIV
Michael E Halwes, Jill M Steinbach-Rankins, Hermann B Frieboes
Although a number of drugs have been developed for the treatment and prevention of human immunodeficiency virus (HIV) infection, it has proven difficult to optimize the drug and dosage parameters. The vaginal tissue, comprised of epithelial, stromal and blood compartments presents a complex system which challenges evaluation of drug kinetics solely through empirical effort. To provide insight into the underlying processes, mathematical modeling and computational simulation have been applied to the study of retroviral microbicide pharmacokinetics...
October 10, 2016: European Journal of Pharmaceutical Sciences
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