The HIV epidemic continues to affect marginalized groups disproportionately, particularly in the United States (US) Southeast, which accounted for 49% of HIV infections in 2022 [1]. Pre-exposure prophylaxis (PrEP) is an essential intervention in reducing the risk of HIV transmission. When taken as a daily pill as prescribed, PrEP decreases the likelihood of infection from sexual contact by approximately 99% and from injection drug use by at least 74%. This study focuses on the implementation of daily oral PrEP through collaborative practice agreements (CPAs), though injectable PrEP may be considered in future efforts [2]. The expansion of PrEP usage is globally recognized as a critical component of a comprehensive approach to reducing new HIV transmissions [3-8]. Despite the proven benefits, the US Southeast faces significant challenges in PrEP accessibility, as highlighted by its 2022 PrEP-to-need ratio (PnR) of 10.0, meaning there are 10 PrEP users for every person diagnosed with HIV. In comparison, the West, Northeast, and Midwest have higher PnRs of 16.2, 21.5, and 15.9, respectively [9]. This low PnR signals an unmet need for PrEP fueled by a backdrop of systemic barriers, including lack of proximity to PrEP providers [10-14], low health insurance coverage, and high cost of medical care [12,14-19], medical mistrust [14,16,20-24], stigma [14,16,21-26], and limited PrEP knowledge among providers and populations at risk of contracting and transmitting HIV [15,16,27]. These barriers continue to hinder PrEP access, uptake, and adherence among individuals at risk from sexual exposure and injection drug use [28-31].

Research has demonstrated that enhancing support for state and local initiatives to increase pharmacy-based access to PrEP can significantly improve the HIV care continuum [32,33]. Pharmacies, as primary access points for prescriptions, can play a crucial role in PrEP acquisition and adherence [33]. Over 89% of Americans reside within 5 miles of a pharmacy, and many consumers frequently visit pharmacies during off-clinic hours, such as weekends, evenings, and holidays [34]. Pharmacies are ideally situated within neighborhoods experiencing high rates of HIV, which are often communities with higher proportions of Black residents and lower income levels [35].

Pharmacists are viewed as trusted sources of health care by community members [33-36]. There is a growing body of evidence showing that community pharmacies can engage with high-risk populations to provide HIV testing [37-40] and counseling to reduce HIV risk behaviors [41-43]. As members of the community that they provide services in, pharmacists have a strong rapport with community members and the potential to reduce stigma when offering HIV services [44-46] in a nonstigmatized setting and concurrently with other nonstigmatized disease screenings [37,38,47]. They also report high willingness and ability to be trained to screen for and dispense PrEP [47-51]. Unfortunately, pharmacy-based PrEP uptake in the Southeastern US faces significant policy-driven barriers that hinder pharmacists’ ability to initiate and manage PrEP care effectively.

Currently, pharmacists’ scopes of services are primarily defined by national- and state-level policies, with many already delivering essential services, such as medication, immunizations, and primary prevention screenings [52,53]. In the US Southeast, local policies often restrict pharmacists from prescribing PrEP, requiring formal linkages with clinicians who can provide telehealth prescriptions [54,55]. Pharmacists and PrEP-prescribing clinicians in every state in the US Southeast can establish linkages called CPAs, which represent a viable pathway to further integrating pharmacists into HIV care [56,57]. CPAs allow pharmacists to work directly with clinicians to provide comprehensive health services, including HIV prevention services, such as PrEP prescribing, HIV testing, and follow-up care [58,59]. This model has the potential to increase the availability of PrEP services and formalize the partnership between pharmacists and clinicians, ensuring that high-risk populations can be effectively and consistently linked to HIV care [60-62]. Furthermore, little is known about provider sentiments toward addressing this barrier. Thus, examining provider willingness to establish CPAs and the various implementation needs for PrEP care linkage in the US Southeast is imperative to maximize this pharmacy-based strategy to Ending the HIV Epidemic (EHE) [7].

Improving collaboration between pharmacists and PrEP-prescribing clinicians requires a thorough understanding of the factors influencing the establishment of CPAs. This study examines policy-level constraints, pharmacy workflows, and clinician engagement to identify barriers and facilitators shaping the integration of PrEP into community pharmacies. To guide this process, we will apply the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, which offers a structured approach to intervention development [63]. The EPIS framework includes 4 stages: Exploration, to identify barriers and facilitators of CPA adoption through stakeholder input; Preparation, to create and adapt a CPA template that supports pharmacy-based PrEP services; Implementation, to pilot the use of CPAs in community pharmacy settings; and Sustainment, to evaluate the long-term factors that influence CPA scalability and effectiveness. This study also integrates the Consolidated Framework for Implementation Research (CFIR), which systematically evaluates 5 domains critical to implementation: intervention characteristics, external influences, internal pharmacy operations, individual roles, and implementation processes [64]. Additionally, the Systems Engineering Initiative for Patient Safety (SEIPS) model will be used to assess how pharmacy work systems, processes, and outcomes interact throughout the implementation of CPAs. SEIPS, often used in pharmacy interventions, such as medication therapy management, emphasizes designing work systems to optimize care delivery [65]. Figure 1 illustrates the conceptual framework for establishing a pharmacist-clinician CPA, integrating CFIR and SEIPS to highlight key factors influencing implementation. By integrating these frameworks, this study aims to provide a detailed understanding of the barriers and opportunities for CPA implementation to improve access to HIV prevention services through pharmacies.

The primary goal of the Collaborative Agreement–based PrEP Using Pharmacists (CAP-UP) study is to develop and evaluate a pharmacist-clinician CPA template and training program to improve access to pharmacy-based PrEP initiation and adherence services in the US Southeast. This study aims to (1) identify and evaluate policy-, pharmacy-, and clinician-level barriers and facilitators to implementing CPAs for PrEP services in community pharmacies, providing actionable insights to enhance PrEP delivery systems; (2) design and test a flexible CPA template that can be adapted across diverse pharmacy settings to facilitate the integration of HIV prevention services and equip pharmacists with the tools needed to deliver comprehensive care; and (3) pilot and assess the implementation of pharmacist-clinician CPAs in community pharmacies, focusing on effectiveness and implementation outcomes, including acceptability, feasibility, and care linkage [64,65]. We will use a hybrid type 1 design that allows for the simultaneous evaluation of implementation and effectiveness outcomes, offering valuable evidence for real-world CPA adoption [66]. In the following sections, we outline the protocol for each aim of CAP-UP.

The CAP-UP study uses a mixed methods, hybrid type 1 design to test the effectiveness and evaluation of establishing CPAs between pharmacists and clinicians for delivering PrEP services in pharmacies. Drawing on the EPIS framework, the study is conducted in three phases: (1) an exploration phase with a mixed methods assessment of barriers and facilitators to CPA establishment, including online surveys with pharmacy staff from across the US Southeast and in-depth interviews (IDIs) with pharmacy policy decision-makers, pharmacy staff, and PrEP-prescribing clinicians in Georgia; (2) a preparation phase to develop a CPA template and resources for pharmacists and clinicians to formalize partnerships for PrEP care provision; and (3) an implementation and sustainment phase to test the CPA template at 10 community pharmacies in neighborhoods with high baseline HIV prevalence, to evaluate its integration in pharmacy and clinic settings. We propose testing a logic model for scaling pharmacy-based PrEP services using pharmacist-clinician CPAs, as outlined in Figure 2.

Ethics approval was obtained from the Emory University Institutional Review Board (STUDY00006422). All procedures involving human participants will adhere to ethical principles and federal regulations for the protection of human participants. Informed consent will be obtained from all participants prior to participation. For the web-based survey, participants will review and electronically agree to a consent form before beginning the survey. For the qualitative interviews, verbal consent will be obtained and documented at the start of each interview. All data will be deidentified prior to analysis. Survey responses will be collected through a secure, password-protected platform, and interview transcripts will have personal identifiers removed during transcription. Study data will be stored on encrypted servers accessible only to authorized research staff. Participants completing the survey will receive a US $20 electronic gift card, and stakeholders participating in interviews will receive a US $50 electronic gift card as compensation. No identifiable images of participants will be included in this publication or any future study materials.

The primary purpose of the exploration phase is to establish an understanding of the policy-, pharmacy-, and clinician-level barriers and facilitators of integrating CPAs into community pharmacies to expand PrEP access.

The primary goal of the preparation phase is to develop a CPA template that is adaptable to various states in the US Southeast.

The primary purpose of the implementation and sustainment phase is to test the implementation of the CPA template at 10 community pharmacies located in neighborhoods with high baseline HIV prevalence and evaluate the integration of this resource in the pharmacy and clinic settings.

Participant recruitment and data collection began in November 2023. As of January 5, 2026, a total of 264 participants have been recruited and have completed phase 1 pharmacy staff surveys, including 27 IDIs. Recruitment and data collection for phase 1 are anticipated to be completed by February 2026, with a target of 300 surveys completed and 68 IDI participants interviewed.

We compiled and analyzed state-specific requirements for CPAs across CAP-UP states (Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee) to develop a standardized yet adaptable CPA template. Data collection involved reviewing the Centers for Disease Control and Prevention CPA Toolkit, state pharmacy board regulations, and existing policies. CPA components were categorized into 3 main domains: scope of agreement, which defines the pharmacist’s clinical authority and prescriptive limitations; legal components, which outline regulatory requirements, including physician oversight and patient inclusion criteria; and administrative components, which detail documentation, data retention, and reporting obligations. Preliminary findings indicate that most states require a defined scope of agreement and prescriptive authority limitations, while supervision requirements and patient inclusion criteria vary, with some states mandating CPAs to name individual patients. Additionally, administrative requirements, such as data retention policies, range from 5 to 10 years. Phase 1 data will be used to refine the initial template, integrating stakeholder feedback to ensure it is tailored to the specific regulatory and operational contexts of each state. These findings will inform the development of a master CPA template with state-specific modifications, which is anticipated to be publicly available by 2026.

Data collection began in winter 2025, and interim and final results are forthcoming.

The CAP-UP study highlights the transformative potential of CPAs in addressing critical gaps in HIV prevention services, particularly in the Southeastern US, where inequities in HIV prevention access remain profound. By leveraging pharmacies as accessible, trusted points of care, CPAs can enhance access to PrEP for disproportionately affected populations, including Black communities and those in underserved areas [1,9,10,35]. This study’s use of the EPIS, CFIR, and SEIPS frameworks ensures a robust analysis of implementation barriers, facilitators, and operational needs, providing a clear pathway for scaling pharmacy-based PrEP services [63-65,73]. The hybrid type 1 design offers an opportunity to simultaneously evaluate implementation and effectiveness outcomes, generating evidence that can inform sustainable, real-world applications of CPAs [65,70]. However, regional policy constraints pose substantial challenges to this effort. Varying state regulations, limitations on pharmacist-prescribing authority, and the complexity of navigating collaborative agreements often hinder the widespread adoption of pharmacy-based PrEP services [61,70,71]. These barriers highlight the urgent need for policy reforms to empower pharmacists and streamline CPA implementation as well as the integration of HIV prevention services via pharmacist-led services [54,55,71]. Until legislation is fully expanded to allow pharmacists prescription authority for PrEP, developing and piloting adaptable CPA templates may create a scalable framework that can be applied across diverse pharmacy settings to enhance PrEP access [56,63,70]. Moreover, the CAP-UP study could inform advocacy for policy changes that empower pharmacists to operate at a higher level, reducing barriers to CPA implementation nationwide [56,71]. This includes addressing state-specific restrictions and fostering collaboration between regulatory boards and policymakers to streamline approval processes [56,71,72]. These advancements have the potential to not only reduce new HIV infections but also strengthen the role of pharmacies as essential health care hubs in underserved communities [7,34-42]

The CAP-UP study has several limitations that should be considered when interpreting its findings. Although efforts are made to recruit an adequate sample of pharmacy staff from each state, the results may not fully represent the experiences and practices of all pharmacies across the US Southeast. Voluntary participation may introduce selection bias, and variability in pharmacy workflows and clinician engagement could influence implementation outcomes. Although the CPA template is designed to be adaptable, significant modifications may be required in certain settings, reducing its potential for standardization. Regulatory barriers specific to the region and stigma surrounding HIV prevention could hinder engagement from both pharmacies and clients. Self-reported data may be affected by recall and social desirability biases, and cost estimates based on assumptions about pharmacists’ time may not reflect actual expenses in all contexts. Limited training, resources, and access to technology may further impede participation and implementation, while delays in recruitment and data collection could disrupt the study timeline.

Despite these limitations, the CAP-UP study addresses critical gaps in access to HIV prevention services by leveraging pharmacist-clinician CPAs to expand pharmacy-based PrEP services in the US Southeast. This approach focuses on improving access for high-risk populations, particularly in communities where systemic barriers and stigma have historically limited health care access. Through the use of a hybrid type 1 design, the study systematically evaluates the barriers and facilitators to implementing CPAs, develops a flexible CPA template tailored to diverse pharmacy settings, and pilots the integration of CPAs in community pharmacies serving high-risk populations. Ultimately, the findings will inform future efforts to integrate pharmacists into HIV prevention strategies, contributing to the goal of reducing inequities and curbing the HIV epidemic in disproportionately affected communities.