Optimizing HIV Therapy: virological monitoring, adherence & cost-effectiveness

描述（由申请人提供）：抗逆转录病毒疗法（ART）对艾滋病毒感染者有巨大的好处，包括降低发病率和死亡率，减少二次传播。在撒哈拉以南非洲，抗逆转录病毒疗法的迅速推广使400多万人接受了治疗。最大限度地提高这些人的治疗效果需要足够的依从性和适当的方案选择。病毒载量（VL）监测是非洲未充分利用的一种方法，但有可能提高长期成果。扩大监测可能对提高依从性、维持治疗疗效、保留治疗选择和控制新出现的耐药菌株至关重要。 从行为上讲，VL监测可能是提高依从性的有力动力。VL向患者传达关于疾病严重程度增加的威胁的重要信息。了解VL增加是一个警告信号，可以改善患者的依从行为。对于耐药突变患者，需要简单的算法来指导决策，并确保及时转换为二线治疗，以最大限度地减少不良结局和耐药病毒的传播。 最大限度地发挥抗逆转录病毒治疗效果的具有成本效益的干预措施必须考虑坚持和抵抗在推动结果方面的作用。全面的成本效益分析为决策者提供了深入的见解，考虑实施监测战略，解决早期大规模启动抗逆转录病毒治疗的后果。Kirschstein-NRSA个人研究金（F30）提案的总体目标是确定撒哈拉以南非洲VL监测的临床和政策影响，促进可持续的，具有成本效益的ART监测的发展，以最大限度地提高治疗效果。 该提案的具体目标是：1）评估提供VL信息对ART依从性的影响; 2）开发预测模型，以识别单个VL升高的耐药者;和3）开发一个可推广的成本效益模型，以a）将床旁、DBS和传统VL监测与当前的护理标准进行比较，和B）对即将到来的护理点测试的设计和定价进行优化评估。拟议的研究包括一项前瞻性队列研究的辅助研究，旨在检查VL信息对ART依从性的影响（目标1）; RCT数据的回顾性分析，以提高识别治疗失败的效率（目标2）;以及可推广的成本效益 分析，为VL监测政策提供信息（目标3）。通过这个研究项目和精心构建的培训计划，学员将实现以下奖学金目标：1）发展计量经济学，临床和行为研究方法的高级技能; 2）获得临床和转化研究技能; 3）发展必要的专业技能，以促进成功的学术生涯。

DESCRIPTION (provided by applicant): Antiretroviral therapy (ART) has enormous benefits for HIV-infected persons, including improved morbidity and mortality and reduced secondary transmissions. In sub-Saharan Africa, rapid scale-up of ART has allowed over four million persons to receive therapy. Maximizing treatment outcomes in these persons requires sufficient adherence and appropriate regimen selection. Viral load (VL) monitoring is one approach that has been underutilized in Africa, but has the potential to enhance long-term outcomes. Expanded monitoring may be critical to improving adherence, maintaining treatment efficacy, preserving therapeutic options, and controlling emerging resistant strains. Behaviorally, VL monitoring may be a potent motivator to improve adherence. The VL communicates important information to the patient regarding the threat of increasing severity of disease. Knowledge of an increased VL is a warning sign that may improve a patient's adherence behavior. For persons with resistance mutations, simple algorithms are needed to guide decisions and ensure prompt conversion to second-line therapy to minimize poor outcomes and transmission of resistant virus. Cost-effective interventions to maximize ART effects must consider the role of adherence and resistance in driving outcomes. Comprehensive cost-effectiveness analyses provide insight for policymakers considering implementation of monitoring strategies, addressing the consequences of early initiation of ART on a larger scale. The overall objective of this Kirschstein-NRSA individual fellowship (F30) proposal is to identify the clinical and policy implications of VL monitoring in sub-Saharan Africa, facilitating the development of sustainable, cost-effective ART monitoring to maximize treatment outcomes. The specific aims of this proposal are: 1) To evaluate the effect of providing VL information on ART adherence; 2) To develop a predictive model to identify persons with resistance from a single elevated VL; and 3) To develop a generalizable cost-effectiveness model to a) compare point-of-care, DBS, and conventional VL monitoring to current standard of care, and b) conduct optimization evaluation for design and pricing of forthcoming point-of-care tests. The proposed research includes an ancillary study of a prospective cohort study designed to examine the effect of VL information on ART adherence (Aim 1); a retrospective analysis of RCT data to improve efficiency in identifying treatment failure (Aim 2); and a generalizable cost-effectiveness analysis to inform VL monitoring policy (Aim 3). Through this research project and a carefully constructed training plan, the trainee will achieve the following fellowship goals: 1) develop advanced skills in econometric, clinical, and behavioral research methods; 2) acquire clinical and translational research skills; and 3) develop professional skills necessary to foster a successful academic career.