Novel Strategy for HIV Drug Resistance Monitoring in Developing Countries.

发展中国家艾滋病毒耐药性监测新战略。

• 批准号: 8467670
• 负责人: CHRISTOPHER F ROWLEY
• 金额: $ 30.09万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-20 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8467670
• 关键词: AIDS/HIV problem; Achievement; Acquired Immunodeficiency Syndrome; Adherence; Adult; Adverse effects; Africa; African; Algorithms; Alleles; Anti-Retroviral Agents; Area; Base Sequence; Biological Assay; Botswana; CD4 Lymphocyte Count; Caring; Clinical; Country; Data; Detection; Developed Countries; Developing Countries; Drug resistance; Effectiveness; Ensure; Epidemic; Gene Mutation; Generations; Genotype; Goals; Government; HIV; HIV Infections; HIV drug resistance; HIV therapy; HIV-1; Health; Housing; Individual; Knowledge; Learning; Methods; Modeling; Monitor; Mutation; Patients; Pattern; Pharmaceutical Preparations; Population; Prevalence; Prevention strategy; Property; Protocols documentation; RNA-Directed DNA Polymerase; Regimen; Research; Research Infrastructure; Resistance; Resistance development; Resource Allocation; Resources; Sampling; Sentinel; Site; Surveillance Methods; Techniques; Testing; Time; Viral; Virus; World Health Organization; antiretroviral therapy; cost; cost effective; design; fight against; improved; innovation; medication compliance; new technology; novel; novel strategies; pol genes; population based; programs; quality assurance; resistance mutation; success; transmission process; virus characteristic

DESCRIPTION (provided by applicant): The increase in antiretroviral use globally to treat HIV infections has been a much needed and worthy achievement as many thousands of lives have been saved by the rapid expansion of treatment. A natural byproduct of the increased use of these medications is the acquisition of drug resistance in patients failing therapy that will ultimately result in transmitted drug resistance. The timing of the increase in transmitted resistance, so that it impacts national antiretroviral therapy (ART) programs, is unclear, but in resource-limited regions, where it is not feasible to test all individuals for drug resistance at the time they enter care, alternative strategies to monitor resistance are needed. We hypothesize that transmitted drug resistance can be monitored with novel strategies in Botswana. In Specific Aim 1, we propose to conduct surveillance for transmitted HIV drug resistance in Botswana for four consecutive years using a surveillance method developed by the World Health Organization (WHO) in addition to our novel strategy of pooling samples and applying highly sensitive assays to detect drug resistance mutations critical to 1st line ART. This strategy will be validated by the standard genotyping results obtained by the WHO protocol. In Specific Aim 2, we restrict this method of pooling samples to only those individuals with recent HIV infection to see if this improves our ability to monitor transmitted drug resistance and also will closely evaluate transmission pairs to learn about the dynamics of transmission between partners. In Specific Aim 3, we will compare a pooling strategy to detect HIV drug resistance with a standard in-house genotyping technique to determine if this approach to genotyping provides meaningful, cost-effective, results prior to ART initiation. The data generated by this technique would again focus on those mutations relevant to 1st line ART to aid clinicians in predicting success of this therapy. The studies to be performed in this research will characterize the current state of transmitted drug resistance in Botswana by conventional and novel techniques and determine the feasibility of new strategies to monitor for the emergence of HIV drug resistance in resource-limited regions; essential components of monitoring to ensure the continued success of the ART program in Botswana.

描述（由申请人提供）：全球增加抗逆转录病毒治疗艾滋病毒感染的使用是一项非常必要和有价值的成就，因为治疗的迅速扩展挽救了成千上万的生命。增加使用这些药物的一个自然副产品是在治疗失败的患者中获得耐药性，这最终将导致传播耐药性。传播的耐药性增加的时间，使它影响国家抗逆转录病毒疗法（ART）计划，是不清楚的，但在资源有限的地区，这是不可行的测试所有个人的耐药性时，他们进入护理，替代战略，以监测耐药性是必要的。我们假设，在博茨瓦纳，可以用新的策略来监测传播的耐药性。具体目标1、我们建议使用世界卫生组织（WHO）开发的监测方法，在博茨瓦纳连续四年监测艾滋病毒耐药性传播情况除了我们的新策略，即合并样本并应用高灵敏度检测方法检测对一线ART至关重要的耐药突变外，该策略将通过WHO获得的标准基因分型结果进行验证。议定书在具体目标2中，我们将这种汇集样本的方法限制在最近感染艾滋病毒的个体中，以了解这是否提高了我们监测传播耐药性的能力，并密切评估传播对，以了解伴侣之间的传播动态。在具体目标3中，我们将比较检测HIV耐药性的合并策略与标准内部基因分型技术，以确定这种基因分型方法是否在ART开始前提供有意义的、具有成本效益的结果。通过该技术生成的数据将再次关注与一线ART相关的突变，以帮助临床医生预测该疗法的成功。在这项研究中进行的研究将通过传统和新技术描述博茨瓦纳传播的耐药性的现状，并确定新战略的可行性，以监测资源有限地区出现的艾滋病毒耐药性;监测的基本组成部分，以确保博茨瓦纳ART计划的持续成功。