Mathematical Modeling Core

数学建模核心

• 批准号: 10599359
• 负责人: ALAN S PERELSON
• 金额: $ 34.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599359
• 关键词: Address; Adverse drug effect; Affect; Aftercare; Bioinformatics; Biological Assay; Blood; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Collaborations; DNA; Data; Data Analyses; Data Set; Development; Drops; Event; Experimental Designs; Fostering; Generations; Goals; HIV; HIV Infections; HIV-1; Immune response; Immune system; Individual; Infection; Infection Control; Kinetics; Laboratories; Length; Measures; Mission; Modeling; Mutation; Natural Killer Cells; Persons; Phase; Plasma; Population; Process; Property; Proviruses; Public Health; Research; Research Project Grants; Research Support; Rest; SIV; Sampling; Shapes; System; T-Cell Depletion; Techniques; Testing; Time; Tissues; Viral; Viremia; Virus; antiretroviral therapy; computing resources; data integration; dynamic system; experimental analysis; innovation; insight; latent HIV reservoir; mathematical model; member; nonhuman primate; novel; predictive modeling; programs; response; simulation; synergism; viral rebound

Summary – Mathematical Modeling Core HIV infection remains an important public health problem. Effective antiretroviral therapy (ART) can control the infection, but lifelong ART is challenging and is encumbered by long-term adverse drug effects. The major challenge to eradicating HIV-1 is the existence of the long-lived latent HIV-1 resevoir. While reservoir eradication is the ultimate goal, to achieve that goal we need greater understanding of the factors underlying the establishment of the reservoir, the composition of the reservoir, the dynamics of the reservoir and if there are specific properties of reservoir cells that could be exploited to enhance their elimination. Following the initiation of ART, the amount of virus in the blood drops dramatically. This is due to the fact that most infected cells die very quickly, and when new infection events are blocked by ART, this decay becomes apparent. However, not all of the infected cells die; some survive and may become part of the stable latent reservoir. This research program will study these decay processes using precise quantitative assays and single cell techniques in hope of understanding whether the decay represents a selection process that shapes the composition of the latent reservoir. The Modeling Core will develop mathematical models to explain these decay processes and how they are related to the dynamics of the latent reservoir. The Core will also provide expertise in experimental design and analysis of experimental results. We hope that this collaborative, quantitative approach will lead to a better understanding of how the reservoir forms and persists and to novel cure strategies.

摘要-数学建模核心