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

描述（由申请人提供）：超过30%的确定的ART合格患者未能开始（FTI）ART，导致早期死亡率，母婴传播和艾滋病疾病的增加。ART启动失败主要基于资源有限环境中的系统条件：1）获得ART资格的CD 4细胞计数的延迟，2）提供者对ART的误解， 在特定患者群体中启动ART的紧迫性，以及3）多次ART前依从性咨询会议和支持要求。我们已经开发了一个多组件的简化ART启动策略（START），该策略基于经验验证的变化模型，该模型部署了1）便携式护理点（POC）CD 4检测和适应性咨询，以启动ART，2）通过教育传播信息，使提供者行为倾向于3）关于FTI的反馈报告，以加强ART的摄取。我们现在建议在随机，通过我们的PEPFAR支持的Mulago-Mbarara联合艾滋病计划（MMJAP），在乌干达的24家诊所进行了受控阶梯楔形试验。目的1：评估START对ART启动的影响。具体来说，我们将比较随机分配到立即和延迟实施START的患者中开始ART的总时间和完成情况。我们将对CD 4 < 50/L的结核病患者、所有世卫组织第4期患者以及CD 4 < 350/L的孕妇进行亚组分析，因为乌干达最近采用了全面抗逆转录病毒疗法作为预防母婴传播的战略。此外，我们计划测量和评价特定的子间隔（例如，患者入组、CD 4检测请求、标本采购等之间）。包括ART启动过程的“解剖学”，以便可以确定干预的具体效率和瓶颈。目标二：通过跟踪社区失访患者，使用补充结局确定评估START对死亡率和其他结局的影响。了解新的实施战略对“硬”终点（如现实环境中的生存率）的因果影响是影响评价的一个关键目标。然而，在非洲的项目设置下，高失访率（即未知结局）导致对结局的偏倚评估。我们的团队已经开发出一种方法来管理失访，该方法基于通过社区中的患者跟踪来积极确定结果。我们将采用这种方法来评估HIV RNA抑制以及死亡率。目标3：评估裁武条约的成本和成本效益。简化的ART启动不仅可以挽救生命，而且还可以提高效率，通过减少每例患者的资源和增加产量的ART。使用目标1和2中获得的有效性和诊所和个人水平的成本数据，我们将估计成本和成本效益的START与标准的护理ART启动。关注的结果将包括以下成本：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;避免残疾调整生命年（DALY）。 公共卫生相关性：在非洲，常规护理中的抗逆转录病毒疗法启动往往不是最佳的：多达20-30%的合格患者未能启动（FTI）抗逆转录病毒疗法，而那些开始启动的患者往往会延迟2-3个月，导致死亡率增加。鉴于非洲的药物依从性总体上很好，确定简化ART启动的战略是 因此，这是一个紧迫的公共卫生优先事项。我们现在建议在乌干达24个PEPFAR支持的诊所进行随机对照、阶梯楔形试验，实施并测试简化的ART启动“START”战略，以减少快速道感染。

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). PUBLIC HEALTH RELEVANCE: ART initiation in routine care in Africa is often suboptimal: up to 20-30% of eligible patients fail to initiate (FTI) ART and those who do start frequently encounter delays of 2-3 months resulting in increased mortality. Given that medication adherence in Africa is in general excellent, identifying strategies to streamline ART initiation is therefore an urgent public health priority. We now propose to implement and test the Streamlined ART Start "START" strategy to reduce FTI in a randomized controlled, stepped-wedge trial of 24 PEPFAR supported clinics in Uganda.