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

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.