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

摘要 口服PrEP非常有效，但未得到充分利用：在美国，符合PrEP资格的个人中只有25%有 处方药。最近批准了卡替格列韦-LA(CAB-LA)，一种长效的注射整合酶抑制剂和 第一种长效注射形式的PrEP，提供了增加摄取的机会。然而，长久以来 停药后不同个体之间CAB-LA的可变半衰期(称为尾部)构成 实施挑战。在尾巴期间，卡替格列韦的水平下降到不再具有保护性但 保持足够的浓度，如果患者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。这种对尾巴的担忧给开出CAB-LA处方的提供者带来了障碍， 限制CAB-LA为结束艾滋病毒流行目标作出贡献的潜力，并加剧#年的差距 PREP摄取和HIV感染。为了减少在尾巴期间感染抗药性艾滋病毒的风险， 建议个人在停用CAB-LA后口服PrEP 12个月或更长时间， 他们有感染艾滋病毒的持续风险。然而，这些建议很难 实施是因为(1)卡替格雷的清除量在不同个体之间变化很大，没有明确的预测因素 直到病毒清除的持续时间和(2)个人可能在尾部误判自己的艾滋病毒风险，导致缺乏艾滋病毒 在个人感染抗药性艾滋病毒的风险最大的情况下进行预防。 在社区利益攸关方的参与下，纽约市卫生和精神卫生部门(NYC DOHMH)、临床医生和患者，我们设计了基于行为的依从性干预Tail-PrEP 经济原则，支持患者保持口服PrEP，只要他们需要，以防止 抗药性。Tail-PrEP带来了一种个性化的药物依从性方法，通过使用生物标记物 为口服PrEP的最短持续时间提供客观、个性化的测量。它是 设计时考虑了可扩展性，允许患者和他们的提供者监控CAB-LA药物浓度 替诺福韦依从性与自行收集的样本在国内。此外，Tail-PrEP是使用 实施研究逻辑模型，阐明了假设干预的方式 影响预期结果(例如，行动机制)、执行战略 将进行干预，并对结果进行评估。 Tail-PrEP研究将评估在小规模试点中干预的可接受性和可行性。学习 结果将首先与当地利益相关者共享，然后再与国家利益相关者共享，并根据他们的反馈进行迭代改进 以增加介入在不同临床情况下可接受和可行的可能性 不同的患者群体。在这个项目结束时，我们的目标是(1)改进的Tail-PrEP干预和 实施战略；以及(2)足够的可接受性和可行性数据，以导致申请R01 支持多点干预实施和有效性混合设计研究中的评估。

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.