The TAIL-PrEP Study: Acceptability and Feasibility of a Tailored Adherence Intervention for safe discontinuation of Long-acting PrEP

TAIL-PrEP 研究：安全停用长效 PrEP 的定制依从性干预措施的可接受性和可行性

• 批准号: 10700242
• 负责人: Kathrine Meyers
• 金额: $ 48.4万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2025-09-17
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700242
• 关键词: AIDS prevention; Address; Adherence; Adolescent and Young Adult; Articulation; Behavior; Biological Markers; Caring; Clinical; Communication; Communities; Counseling; Data; Disparity; Drug Monitoring; Drug resistance; Eligibility Determination; Ensure; Epidemic; Evaluation; Feedback; Goals; HIV; HIV Infections; HIV drug resistance; HIV resistance; HIV risk; HIV/AIDS; Half-Life; Health; Health Benefit; Health behavior; Home; Hybrids; Individual; Injectable; Injecting drug user; Injections; Integrase; Integrase Inhibitors; Intervention; Interview; Laboratory Scientists; Learning; Logic; Measures; Mental Health; Methods; Mind; Modeling; Monitor; Motivation; National Institute of Mental Health; New York; New York City; Oral; Outcome; Patients; Persons; Pharmaceutical Preparations; Population; Presbyterian Church; Prevention; Prevention program; Prevention strategy; Process; Provider; Public Health; Recommendation; Research; Research Design; Research Priority; Resistance; Resources; Risk; Sampling; Science; Services; Side; Site; Specimen; Tail; Tenofovir; Testing; Time; United States National Institutes of Health; Universities; acceptability and feasibility; behavioral adherence; behavioral economics; design; effectiveness evaluation; effectiveness/implementation design; experience; health equity; housing instability; implementation barriers; implementation design; implementation evaluation; implementation intervention; implementation research; implementation strategy; multidisciplinary; novel; patient population; personalized medicine; pill; pre-exposure prophylaxis; preference; prevent; risk mitigation; routine care; social; substance use; theories; tool; transmission process; treatment strategy; uptake; willingness

Abstract Oral PrEP is highly effective but underutilized: only 25% of individuals eligible for PrEP in the US have a prescription. Recent approval of cabotegravir-LA (cab-LA), a long-acting injectable integrase inhibitor and the first long-acting injectable form of PrEP, presents an opportunity to increase uptake. However, the long and variable half-life of cab-LA across different individuals after discontinuation (called the “tail”) poses an implementation challenge. During the tail, cabotegravir levels decline to levels that are no longer protective but remain in sufficient concentration that if a patient were to acquire HIV during this time, they could select for integrase-inhibitor resistance. This concern about the tail presents a barrier to providers prescribing cab-LA, limiting the potential for cab-LA to contribute to End the HIV Epidemic targets and exacerbating disparities in PrEP uptake and HIV infection. To mitigate the risk of acquiring drug-resistant HIV infection during the tail, individuals are advised to use oral PrEP for 12 months or longer after discontinuing cab-LA and for as long as they have ongoing risk of becoming infected with HIV. However, these recommendations are difficult to implement because (1) clearance of cabotegravir is highly variable across individuals with no clear predictors of duration until clearance and (2) individuals may misjudge their HIV risk during the tail, leading to a lack of HIV prevention when individuals are at greatest risk for drug-resistant HIV infection. With input from community stakeholders, New York City Department of Health and Mental Hygiene (NYC DOHMH), clinicians, and patients, we designed TAIL-PrEP, an adherence intervention based on behavioral economic principles, to support patients in remaining on oral PrEP for as long as they need to in order to prevent drug resistance. TAIL-PrEP brings a personalized medicine approach to adherence, by using biomarkers to provide an objective, individualized measure for the minimum duration for which oral PrEP is indicated. It is designed with scalability in mind, allowing patients and their providers to monitor cab-LA drug concentrations and tenofovir adherence with samples self-collected at home. Additionally, TAIL-PrEP was designed using an Implementation Research Logic Model that articulates the ways in which the intervention is hypothesized to impact the desired outcomes (e.g., mechanisms of action), the implementation strategies by which the intervention will be delivered, and the outcomes that will be assessed. The TAIL-PrEP Study will evaluate the acceptability and feasibility of the intervention in a small pilot. Study results will be shared first with local, then national stakeholders, and iteratively refined based on their feedback to increase the likelihood that the intervention will be acceptable and feasible in diverse clinical contexts serving diverse patient populations. At the end of this project, we aim to have (1) a refined TAIL-PrEP intervention and implementation strategy; and (2) sufficient acceptability and feasibility data to lead to an application for an R01 to support evaluation in a multi-site intervention implementation and effectiveness hybrid-design study.

摘要 口服PrEP非常有效，但未得到充分利用：在美国，只有25%的符合PrEP条件的人有 处方.最近批准的卡替格韦-LA（cab-LA）是一种长效可注射整合酶抑制剂， 第一个长效注射形式的PrEP，提供了一个增加吸收的机会。然而，长期以来， 停药后不同个体之间cab-LA的可变半衰期（称为“尾部”）造成了 实施挑战。在尾部，cabotegravir水平下降到不再具有保护作用的水平， 保持足够的浓度，如果病人在这段时间内感染艾滋病毒，他们可以选择 整合酶抑制剂抗性。这种对尾部的担忧给开cab-LA处方的供应商带来了障碍， 限制了cab-LA为结束艾滋病毒流行目标做出贡献的潜力，并加剧了 PrEP摄取和HIV感染。为了降低在尾部获得耐药性HIV感染的风险， 建议个人在停用cab-LA后使用口服PrEP 12个月或更长时间， 他们有感染艾滋病毒的风险。然而，这些建议很难 实施的原因是（1）卡替拉韦的清除率在个体间差异很大，没有明确的预测因子 持续时间，直到清除和（2）个人可能会误判其艾滋病毒的风险在尾巴，导致缺乏艾滋病毒 当个体处于耐药性艾滋病毒感染的最大风险时进行预防。 在社区利益相关者的投入下，纽约市卫生和心理卫生部（NYC DOHMH），临床医生和患者，我们设计了TAIL-PrEP，这是一种基于行为干预的依从性干预。 经济原则，支持患者在需要时继续口服PrEP，以预防 耐药性TAIL-PrEP通过使用生物标志物， 为口服PrEP的最短持续时间提供客观，个性化的措施。是 设计时考虑了可扩展性，允许患者及其提供者监测cab-LA药物浓度 和替诺福韦依从性与在家自行采集的样本。此外，TAIL-PrEP设计使用 实施研究逻辑模型，阐明了假设干预的方式， 影响期望的结果（例如，行动机制），执行战略， 将提供干预措施，并评估结果。 TAIL-PrEP研究将在小型试点中评估干预的可接受性和可行性。研究 成果将首先与地方利益相关者分享，然后与国家利益相关者分享，并根据他们的反馈不断完善 增加干预在不同临床环境中可接受和可行的可能性， 不同的患者群体。在该项目结束时，我们的目标是（1）完善TAIL-PrEP干预， 实施策略;及（2）有足够的可接受性及可行性数据，以申请R 01 支持多中心干预实施和有效性混合设计研究中的评价。