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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 暴露前的抗逆转录病毒预防措施对疾病发展的潜在影响 和异性传播人类免疫缺陷病毒(HIV)药物 阻力是未知的，也没有被建模。该项目将调查 抗逆转录病毒药物预防对HIV药物流行模式的影响 使用新一代数学和计算模型的阻力 代表现实的生物学、人口学、流行病学和行为学 构成艾滋病毒抗药性动态的异质性。这些创新之处 模型：i)合并血浆病毒血症、CD4细胞下降、艾滋病毒疾病的变异 抗逆转录病毒的进展、传染性、危险行为和效果 个人内部和个人之间的化学预防；ii)模拟不同的策略 使用化学预防；以及iii)预测艾滋病毒耐药性的结果 人口水平。我们的长期目标是使用建模和模拟来设计 有助于控制全球艾滋病毒流行的公共卫生干预战略。 中心假设是，以特定的人群为目标 传播和获得艾滋病毒感染的风险可以将艾滋病毒药物的传播降至最低 抵抗。建议的具体目标是：i)在以下情况下模拟艾滋病毒流行 抗逆转录病毒化疗预防的不同方案实施及分析 艾滋病毒耐药性的预测模式；ii)确定艾滋病毒耐药性的关键决定因素 人类免疫缺陷病毒耐药性预测模式及预测评价 不确定性；以及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，因为它具有多个 将使用建模方法和建模比例来模拟 不同抗逆转录病毒化疗预防策略对发病率和流行率的影响 在资源有限的情况下，艾滋病毒耐药问题日益严重。我们的发现应该有助于确定 艾滋病毒耐药性传播的关键决定因素和最有效的 抗逆转录病毒化学预防战略，以遏制全球艾滋病毒流行和 抗药性。

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.