Novel Strategy for HIV Drug Resistance Monitoring in Developing Countries.

描述（由申请人提供）：在全球范围内，抗逆转录病毒治疗艾滋病毒感染的使用增加是一项非常需要和有价值的成就，因为治疗的迅速扩大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治疗失败的患者获得耐药性，最终将导致传播性耐药性。传播性耐药性增加的时间尚不清楚，从而影响到国家抗逆转录病毒治疗规划，但在资源有限的地区，不可能在接受治疗时对所有个体进行耐药性检测，因此需要采用其他策略来监测耐药性。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。在具体目标1中，我们建议使用世界卫生组织（WHO）开发的监测方法对博茨瓦纳传播的艾滋病毒耐药性进行连续四年的监测，此外我们还采用了汇集样本和应用高灵敏度测定法的新策略来检测对一线抗逆转录病毒治疗至关重要的耐药性突变。世卫组织方案获得的标准基因分型结果将对这一战略进行验证。在Specific Aim 2中，我们将这种汇集样本的方法限制为仅针对近期感染艾滋病毒的个体，以了解这是否提高了我们监测传播耐药性的能力，并将密切评估传播对，以了解伴侣之间的传播动态。在具体目标3中，我们将比较用于检测艾滋病毒耐药性的汇集策略与标准的内部基因分型技术，以确定这种基因分型方法是否在开始抗逆转录病毒治疗之前提供有意义的、具有成本效益的结果。这项技术产生的数据将再次集中在与一线抗逆转录病毒治疗相关的突变上，以帮助临床医生预测这种治疗的成功。在这项研究中进行的研究将通过传统技术和新技术描述博茨瓦纳传播耐药性的现状，并确定监测资源有限地区出现的艾滋病毒耐药性的新战略的可行性；这是监测的重要组成部分，以确保抗逆转录病毒治疗方案在博茨瓦纳继续取得成功。

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.