Improving HIV pre-exposure prophylaxis (PrEP) adherence and retention in care: Recommendation development from a national PrEP programme

Introduction HIV pre-exposure prophylaxis (PrEP) is a key component of HIV combination prevention. Effective prevention needs people to adhere to PrEP during periods of risk and remain in care. However, relevant models of care are under-researched. Using data from the first two years of Scotland’s PrEP programme, we explored barriers and facilitators to PrEP adherence and retention in care and systematically developed evidence-based, theoretically-informed recommendations to enhance future adherence and retention. Methods We conducted semi-structured interviews and focus groups (09/2018-07/2019) with geographically and demographically diverse patients who were either using/declined/stopped or had been assessed as ineligible for PrEP (n=39), healthcare professionals involved in PrEP provision (n= 54), non-governmental organisation service users (n=9) and staff (n=15) across Scotland. We used thematic analysis to map key barriers and facilitators to priority areas that could enhance adherence and retention in care. Next, we used analytic tools from implementation science (Theoretical Domains Framework, Intervention Functions, Behaviour Change Technique Taxonomy, APEASE criteria) and expert opinion to systematically generate recommendations to enhance future PrEP adherence and retention in care. Results Barriers and facilitators to adherence and retention in care were diverse and multi-layered. Barriers included perceived complexity of event-based dosing, the tendency for users to stop PrEP before seeking professional support, troublesome side-effects, limited flexibility in the settings, timings, and nature of appointments for follow up, enduring PrEP-related stigma and emerging stigmas around not using PrEP. Facilitators included flexible appointment scheduling, reminders, and processes to follow up non-attenders. We generated 25 wide-ranging but specific recommendations for key stakeholders, for example, emphasising the benefits of PrEP reviews and providing appointments flexibly within individualised PrEP care; using clinic systems to remind/recall PrEP users for review; supporting PrEP conversations among sexual partners; clear guidance on event-based dosing; encouraging/commitment to good PrEP citizenship; and detailed discussion on managing side-effects and care/coping planning activities. Conclusions PrEP adherence and retention in care is challenging for many people. Such challenges reduce the benefits of PrEP at individual and population levels. Our findings identify and provide solutions to where and how collaborative interventions across public health, clinical, and community practice could address these challenges. ### Competing Interest Statement The investigators named have no financial interests that impact on their responsibilities towards the scientific value or potential publishing activities associated with the study. However, the team has other interests within the field including various roles relating to HIV and sexual health within Government (Steedman, Estcourt, Nandwani, Clutterbuck), policy generation (Steedman, Nandwani, Estcourt, Saunders, Young, Flowers, HIV Scotland), practice (Steedman, Estcourt, Nandwani, Clutterbuck, Saunders) and advocacy (Young, HIV Scotland). PF reports research grants from National Institute of Health Research UK, Chief Scientist Office of Scotland. CSE, RN, JF, JM, JS, IY, DC, NS, LM & JD report no competing interests. ### Funding Statement This work was funded through Scottish Chief Scientist Office grant reference HIPS/17/47 Optimising services for people at highest risk of HIV: Developing best practice in delivering HIV pre-exposure prophylaxis (PrEP) through evaluation of early implementation across Scotland. The grant ran from June 2018 to October 2020. During this study, LMcD was funded by the UK Medical Research Council and Chief Scientist Office of the Scottish Government Health and Social Care Directorates at the MRC/CSO Social & Public Health Sciences Unit, University of Glasgow (MC\_UU\_12017/11, SPHSU11; MC\_UU\_00022/3, SPHSU18). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Glasgow Caledonian University Research Ethics Committee (HLS/NCH/17/037, HLS/NCH/17/038, HLS/NCH/17/044) and the South East Scotland National Health Service Research Ethics Committee (18/SS/0075, R&D GN18HS368) provided ethical approval. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data that supports the findings and suggestions of this study are explained within the the supplementary material for this article, which presents elements of the original dataset. * APEASE : Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity BBV : Blood borne viruses BCT : Behaviour Change Technique BCTT : Behaviour Change Technique Taxonomy BCW : Behaviour Change Wheel GBMSM : Gay, bisexual, and other men who have sex with men HIV : Human immunodeficiency virus PrEP : Pre-exposure prophylaxis STI : Sexually transmitted infection TDF : Theoretical Domains Framework