HIV - Emergence of Drug Resistance

HIV - 耐药性的出现

• 批准号: 8048080
• 负责人: Sally Margaret Blower
• 金额: $ 69.59万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8048080
• 关键词: Abbreviations; Acquired Immunodeficiency Syndrome; Africa; Anti-Retroviral Agents; Award; Classification; Complex; Data; Data Analyses; Data Set; Drug Design; Drug resistance; Ensure; Epidemic; Epidemiology; Equation; Ethics; Europe; Evolution; Female; Future; Gender; Grant; HIV; Health Personnel; Health Policy; Health Services Accessibility; Health care facility; Healthcare; Individual; Interruption; Intervention; Lamivudine; Linear Models; Link; Modeling; Multi-Drug Resistance; Nevirapine; Nucleosides; Operations Research; PTPN6 gene; Paper; Pharmaceutical Preparations; Policy Maker; Prophylactic treatment; Protease Inhibitor; Public Health; Publications; Publishing; Recording of previous events; Regimen; Research; Research Methodology; Research Technics; Resistance; Resource Allocation; Resources; Reverse Transcriptase Inhibitors; Sampling; San Francisco; Simplexvirus; South Africa; Stavudine; Structure; Tenofovir; Trees; Tuberculosis; United States; Vertical Disease Transmission; Virus Diseases; Work; World Health Organization; Zidovudine; antiretroviral therapy; base; efavirenz; mathematical model; men who have sex with men; microbicide; multiple drug use; non-nucleoside reverse transcriptase inhibitors; pandemic disease; prophylactic; public health relevance; resistant strain; sex; transmission process

DESCRIPTION (provided by applicant): This application is to renew a project focused on using mathematical models to understand and predict the emergence of drug resistance to antiretrovirals (ARVs) for the treatment of Human Immunodeficiency Virus (HIV). As the usage rate of ARVs in resource-poor regions is increasing, high levels of drug resistance potentially could emerge and have a devastating impact on public health worldwide, derailing global plans to provide this treatment to many millions of HIV-infected individuals. Our proposed projects will extend the work of the current award, which showed the value of using mathematical models to understand the temporal dynamics of drug-resistant strains of HIV in the United States (US), and for predicting the magnitude of resistance in this setting. In the renewal our work will be extended by combining mathematical modeling with statistical analysis of datasets collected by collaborating groups in the US, Europe and Africa. We will have access to data on drug resistance and important related variables from large scale epidemiological and treatment studies conducted in these three continents. In resource-poor settings, such as Africa, drugs will be limited and thus demand will often greatly exceed supply. We will investigate the problems of allocating ARVs in Africa by using operation research (OR) techniques. We have three Specific Aims. Aim 1: to understand the emergence, explain the present, and predict the evolution of, complex epidemics of drug-resistant strains of HIV in the US and Europe. Aim 2: to predict the evolution of epidemics of drug-resistant strains, as a result of first- line regimens and prophylactic use of ARVs, in Africa. Aim 3: to evaluate the consequences of allocation of scarce HIV healthcare resources in Africa. To achieve this aim we will use models to evaluate the epidemiological and ethical consequences of gender-inequities in access to treatment, assess the epidemiological and ethical impact of treatment priority criteria, and determine healthcare resource allocation strategies that ensure sustainability. Our studies in the renewal will link transmission modeling, OR techniques and statistical analyses; our analyses will take advantage of the extraordinary data sets provided by our collaborators in the US, Europe and Africa. PUBLIC HEALTH RELEVANCE: The emergence and control of drug-resistant strains of HIV is now a global problem. The epidemiology of this problem is complex, and the future of the HIV epidemic is unknown. Our projects focus on using mathematical models to understand, explain, and predict, the evolution of complex epidemics composed of drug-resistant strains of HIV in the US, Europe and Africa. The rollout of antiretrovirals in Africa is just beginning; however demand for drugs greatly exceeds supply. We will, by using mathematical models, evaluate the epidemiological and ethical consequences of allocation of the scarce supply of antiretrovirals in Africa. Our studies are based upon both mathematical modeling and data analyses. Our analyses will take advantage of the extraordinary data sets provided by our collaborators in the US, Europe and Africa. Our results will have direct relevance for health policy makers.

描述（由申请人提供）：本申请旨在更新一个项目，该项目的重点是使用数学模型来了解和预测人类免疫缺陷病毒（HIV）治疗中抗逆转录病毒药物（ARV）耐药性的出现。随着资源贫乏地区抗逆转录病毒药物使用率的增加，可能出现高水平的耐药性，对全世界的公共卫生产生破坏性影响，使向数百万艾滋病毒感染者提供这种治疗的全球计划脱轨。我们提出的项目将扩展目前奖项的工作，该奖项显示了使用数学模型来了解美国艾滋病毒耐药菌株的时间动态以及预测这种情况下耐药性的程度的价值。在更新中，我们的工作将通过将数学建模与美国，欧洲和非洲合作小组收集的数据集的统计分析相结合来扩展。我们将从这三大洲开展的大规模流行病学和治疗研究中获得有关耐药性和重要相关变量的数据。在非洲等资源贫乏的地区，药物有限，因此需求往往大大超过供应。我们将利用运筹学（OR）技术调查非洲抗逆转录病毒药物的分配问题。我们有三个具体目标。目标1：了解艾滋病毒耐药株在美国和欧洲的出现，解释目前的情况，并预测其演变。目标2：预测非洲一线治疗和预防性使用抗逆转录病毒药物后耐药菌株流行的演变。目标3：评估非洲稀缺的艾滋病毒保健资源分配的后果。为了实现这一目标，我们将使用模型来评估在获得治疗方面的性别不平等的流行病学和伦理后果，评估治疗优先标准的流行病学和伦理影响，并确定确保可持续性的医疗资源分配策略。我们的研究将把传播建模、OR技术和统计分析联系起来;我们的分析将利用我们在美国、欧洲和非洲的合作者提供的非凡数据集。 公共卫生相关性：艾滋病毒耐药株的出现和控制现在是一个全球性问题。这个问题的流行病学是复杂的，艾滋病毒流行病的未来是未知的。我们的项目侧重于使用数学模型来理解，解释和预测，在美国，欧洲和非洲的艾滋病毒耐药株组成的复杂流行病的演变。抗逆转录病毒药物在非洲的推广才刚刚开始;然而，对药物的需求远远超过供应。我们将利用数学模型，评估在非洲分配稀缺的抗逆转录病毒药物的流行病学和伦理后果。我们的研究是基于数学建模和数据分析。我们的分析将利用我们在美国、欧洲和非洲的合作者提供的非凡数据集。我们的研究结果将对卫生政策制定者有直接的意义。