Reducing Failure-to-Initiate ART: Streamlined ART Start Strategy (START)

描述(由申请人提供)：超过30%的符合抗逆转录病毒治疗资格的患者未能启动(FTI)抗逆转录病毒治疗，导致早期死亡率、母婴传播和艾滋病发病率增加。抗逆转录病毒治疗启动的失败主要基于资源有限的情况下的系统条件：1)获得抗逆转录病毒治疗资格的CD4细胞计数的延迟，2)提供者对 在特定患者群体中启动抗逆转录病毒治疗的紧迫性，以及3)多个抗逆转录病毒治疗前坚持咨询会议和支持要求。我们开发了一种基于经验验证的变化模型的多组件简化ART START策略(START)，该模型部署了1)便携式护理点(POC)CD4检测和适当的咨询以支持ART START，2)通过教育传播信息以促进提供者行为，以及3)关于FTI的反馈报告，以加强对ART的理解。我们现在建议通过我们的PEPFAR支持的穆拉戈-姆巴拉拉联合艾滋病计划(MMJAP)在乌干达的24家诊所进行随机对照阶梯楔形试验来测试这种干预措施。目的1：评价START对艺术启蒙的影响。具体地说，我们将比较随机到立即实施和推迟实施START的患者的ART启动的总体时间和完成性。我们将对结核病患者和CD4350/？L患者进行亚组分析，这些患者都是世卫组织4期患者，鉴于乌干达最近将全面的抗逆转录病毒疗法作为预防母婴传播的策略，我们将对CD4350/？L的孕妇进行亚组分析。此外，我们计划测量和评估特定的亚组间隔(例如，患者登记、请求CD4T检测、购买标本等之间的间隔)。这包括对ART启动过程的“解剖”，以便能够确定干预中的具体效率和瓶颈。目的2：评估START对死亡率和其他结果的影响，通过跟踪社区中失去随访的患者来补充结果确定。了解新的执行战略对“硬”端点的因果影响，如在现实环境中的生存，是影响评估的一个关键目标。然而，在非洲的项目环境下，后续行动的高损失(即未知结果)导致对结果的偏见评估。我们小组已经开发了一种方法来管理丢失到随访的方法，该方法基于通过社区中的患者跟踪积极确定结果。我们将采用这种方法来评估HIV RNA抑制和死亡率。目标3：评估《削减战略武器条约》的成本和成本效益。简化的ART启动不仅可以挽救生命，还可以通过减少每位患者的资源和增加ART的产量来提高效率。利用目标1和目标2中获得的有效性以及临床和个人层面的成本计算数据，我们将评估START与ART启动护理标准的成本和成本效益。感兴趣的结果将包括单位成本：确认符合ART标准；ART启动；病毒学抑制；避免死亡；避免垂直感染；以及避免残疾调整生命年(DALY)。

DESCRIPTION (provided by applicant): Over 30% of identified ART-eligible patients fail to initiate (FTI) ART resulting in increased rates of early mortality, MTCT and AIDS illnesses. Failures in ART initiation are predominantly based in the systems conditions in resource limited settings: 1) delays in obtaining CD4 cell counts for ART eligibility, 2) provider misconceptions of the urgency of ART initiation among specific patient groups, and 3) multiple pre-ART adherence counseling sessions and support requirements. We have developed a multi-component Streamlined ART Start Strategy (START) based on an empirically validated model of change that deploys 1) portable point of care (POC) CD4 testing and adapted counseling to enable ART start, 2) dissemination of information through education that predisposes provider behavior and 3) feedback reporting on FTIs that reinforces uptake of ART. We now propose to test this intervention in a randomized, controlled stepped-wedge trial of 24 clinics in Uganda through our PEPFAR supported Mulago-Mbarara Joint AIDS Program (MMJAP). Aim 1: Evaluate the effect of START on ART initiation. Specifically, we will compare the overall time to and completeness of ART initiation among those randomized to immediate and delayed implementation of START. We will conduct subgroup analyses in patients with TB and a CD4 < 50/¿l, all WHO Stage 4 patients and - given Uganda's recent adoption full ART as a strategy for pMTCT - pregnant women with a CD4 < 350/¿l. In addition, we plan to measure and evaluate the specific sub-intervals (e.g. between patient enrollment, request for CD4 testing, procurement of the specimen, etc.) that comprise the "anatomy" of the ART initiation process so that specific efficiencies and bottlenecks in the intervention can be identified. Aim 2: Evaluate the effect of START on mortality and other outcomes using supplemental outcome ascertainment through tracking patients who are lost to follow up in the community. Understanding the causal effect of a new implementation strategy on "hard" endpoints such as survival in real-world settings is a key objective of impact evaluation. Under program settings in Africa, however, high loss to follow-up (i.e. unknown outcomes) leads to biased assessment of outcomes. Our group has developed an approach to manage loss to follow-up based on active ascertainment of outcomes through patient tracking in the community. We will adapt this method to evaluate HIV RNA suppression as well as mortality. Aim 3: Assess the cost and cost-effectiveness of START. Streamlined ART initiation may not only save lives but also increase efficiency, by decreasing resources per patient and increasing yield to ART. Using effectiveness obtained in Aims 1 and 2 and clinic and individual level costing data, we will estimate the cost and cost-effectiveness of START versus standard of care for ART initiation. Outcomes of interest will include cost per: confirmation of meeting ART criteria; ART initiation; virologic suppression; averted death; averted vertical infection; and averted Disability-Adjusted Life Year (DALY).