IMPACT OF ANTIRETROVIRAL PREVENTION ON EMERGENCE AND SPREAD OF HIV DRUG RESISTA

抗逆转录病毒预防对艾滋病毒耐药性出现和传播的影响

• 批准号: 8171780
• 负责人: John W Mellors
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171780
• 关键词: Anti-Retroviral Agents; Behavioral; Biological; CD4 Positive T Lymphocytes; Chemoprophylaxis; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Development; Disease Progression; Drug resistance; Epidemic; Epidemiology; Funding; Generations; Goals; Grant; HIV; Heterogeneity; Heterosexuals; Incidence; Individual; Institution; Intervention; Modeling; Outcome; Pattern; Persons; Pharmaceutical Preparations; Plasma; Population; Prevalence; Prevention; Prophylactic treatment; Public Health; Research; Research Personnel; Resources; Risk Behaviors; Simulate; Source; Uncertainty; United States National Institutes of Health; Variant; Viremia; Virus Diseases; design; high risk; innovation; models and simulation; novel; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The potential impact of antiretroviral pre-exposure prophylaxis on the development and heterosexual transmission of human immunodeficiency virus (HIV) drug resistance is unknown and has not been modeled. This project will investigate the effect of antiretroviral chemoprophylaxis on the epidemiologic patterns of HIV drug resistance using a new generation of mathematical and computational models that represent realistic biological, demographic, epidemiologic and behavioral heterogeneities that underlie the dynamics of HIV drug resistance. These innovative models: i) incorporate variation in plasma viremia, CD4 cell decline, HIV disease progression, infectiousness, risk behavior, and effect of antiretroviral chemoprophylaxis both within and among individuals; ii) simulate different strategies of chemoprophylaxis use; and iii) predict HIV drug resistance outcomes at the population level. Our long term goal is to use modeling and simulation to design public health intervention strategies that will help control the global HIV epidemic. The central hypothesis is that targeting specific subpopulations of persons at highest risk for transmitting and acquiring HIV infection can minimize the spread of HIV drug resistance. The specific aims proposed are: i) to simulate an HIV epidemic under different scenarios of antiretroviral chemoprophylaxis implementation and analyze the predicted patterns of HIV drug resistance; ii) to identify the key determinants of the predicted patterns of HIV drug resistance and evaluate the prediction uncertainty; and iii) to determine the sensitivity of the model predictions to modeling framework and assumptions. The proposed research is novel in that multiple modeling approaches and modeling scales will be used to simulate the effect of different antiretroviral chemoprophylaxis strategies on the incidence and prevalence of HIV drug resistance in resource-limited settings. Our findings should help identify the key determinants for spread of HIV drug resistance and the most effective antiretroviral chemoprophylaxis strategies to curb both the global HIV epidemic and drug resistance.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 抗逆转录病毒暴露前预防对发育的潜在影响 人类免疫缺陷病毒 (HIV) 药物的异性传播 电阻未知且尚未建模。该项目将调查 抗逆转录病毒药物预防对艾滋病毒流行病学模式的影响 使用新一代数学和计算模型来抵抗 代表现实的生物学、人口统计、流行病学和行为学 HIV耐药性动态背后的异质性。这些创新的 模型：i) 纳入血浆病毒血症、CD4 细胞下降、HIV 疾病的变异 进展、传染性、危险行为和抗逆转录病毒药物的作用 个体内部和个体之间的化学预防； ii) 模拟不同的策略 化学预防的使用； iii) 预测 HIV 耐药结果 人口水平。我们的长期目标是使用建模和仿真来设计 公共卫生干预战略将有助于控制全球艾滋病毒流行。 中心假设是，针对最高人口的特定亚群 传播和获得艾滋病毒感染的风险可以最大限度地减少艾滋病毒药物的传播 反抗。提出的具体目标是： i) 模拟艾滋病毒流行情况 抗逆转录病毒化学预防的不同场景实施和分析 HIV 耐药性的预测模式； ii) 确定关键决定因素 HIV耐药性的预测模式并评估预测 不确定; iii) 确定模型预测对建模的敏感性 框架和假设。拟议的研究是新颖的，因为多重 建模方法和建模尺度将用于模拟效果 不同的抗逆转录病毒化学预防策略对发病率和患病率的影响 资源有限环境中艾滋病毒耐药性的研究。我们的发现应该有助于确定 HIV耐药性传播的关键决定因素和最有效的 遏制全球艾滋病毒流行的抗逆转录病毒化学预防策略 耐药性。