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

说明(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，包括改善发病率和死亡率，减少二次传播。在撒哈拉以南非洲，抗逆转录病毒治疗的迅速扩大使400多万人得以接受治疗。要最大限度地提高这些患者的治疗结果，需要足够的依从性和适当的方案选择。病毒载量(VL)监测是一种在非洲未得到充分利用的方法，但有可能提高长期成果。扩大监测可能对提高依从性、维持治疗效果、保存治疗选择和控制新出现的耐药菌株至关重要。 在行为上，VL监测可能是提高依从性的有力动机。VL向患者传达有关疾病日益严重的威胁的重要信息。知道VL增加是一个警告信号，可能会改善患者的依从性行为。对于具有抗药性突变的人，需要简单的算法来指导决策并确保迅速转换到二线治疗，以最大限度地减少不良结果和抗药性病毒的传播。 要最大限度地发挥抗逆转录病毒治疗的效果，成本有效的干预措施必须考虑坚持和抵制在推动结果方面的作用。全面的成本效益分析为考虑实施监测战略的政策制定者提供了洞察力，解决了在更大范围内尽早启动抗逆转录病毒药物治疗的后果。这项Kirschstein-NRSA个人奖学金(F30)建议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、成本效益高的ART监测的发展，以最大限度地提高治疗结果。 这项建议的具体目标是：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升高的抵抗者；以及3)开发可推广的成本-效果模型，以a)将护理点、DBS和传统的VL监测与当前的护理标准进行比较，以及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，旨在研究VL信息对ART依从性的影响(目标1)；对随机对照试验数据进行回顾分析，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 分析以告知VL监控政策(目标3)。通过这项研究项目和精心设计的培训计划，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方面的高级技能；2)获得临床和翻译研究技能；3)发展促进成功学术生涯所需的专业技能。 公共卫生相关性：最大限度地发挥艾滋病毒药物的潜在益处，对于改善艾滋病毒感染者接受治疗的长期结果至关重要。监测艾滋病毒患者血液中的病毒数量提供了关于一个人对治疗的反应的重要信息，但在撒哈拉以南非洲接受艾滋病毒治疗的400万人中，只有一小部分人进行了常规监测。这项研究将评估病毒监测对撒哈拉以南非洲坚持使用艾滋病毒药物的影响，并审查广泛实施以提供撒哈拉以南非洲基于证据的艾滋病毒治疗监测指南的成本效益。

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. PUBLIC HEALTH RELEVANCE: Maximizing the potential benefits of HIV medicine is critical to improve long-term outcomes for HIV-infected patients on treatment. Monitoring the amount of virus in an HIV patient's blood provides vital information about a person's response to therapy, but only a fraction of the four million persons on HIV treatment in sub-Saharan Africa have routine monitoring. This study will evaluate the impact of viral monitoring on adherence to HIV medicines in sub-Saharan Africa and examine the cost-effectiveness of widespread implementation to inform evidence-based HIV-therapy monitoring guidelines in sub-Saharan Africa.