Abstract
Background: Pre-exposure prophylaxis (PrEP) guideline implementation varies widely across countries as a result of differences in health systems, resources, and HIV priorities. Since 2016, oral PrEP has been available to key populations, yet limited evidence exists on how implementation challenges differ across contexts.
Objectives: This review aimed to explore the processes and challenges in the implementation of PrEP guidelines globally.
Method: An integrative review method was used by searching electronic databases, including PubMed, Medline, EBSCOhost, CINAHL, and Google Scholar, to extract the data. We included qualitative, quantitative, and mixed-method studies relevant to the global implementation of PrEP published in peer-reviewed English journals from 2019 through 2025.
Results: This study emphasises that worldwide PrEP implementation is complex and adaptable, involving progressive provider engagement, task-shifting, and health system integration. Stigma and misunderstandings about PrEP, including structural barriers such as a lack of coverage recognition and supply chain difficulties at odds with the maintenance phase needed to scale up availability, are challenges.
Conclusion: Progress on global PrEP coverage has been blunted by persisting challenges in dismantling structural, financial, and geopolitical blockades to universal access. The model will work if it is implemented with community outreach and creative service delivery, including education, training, and outreach. Structural inequalities need to be considered and crisis-affected communities prioritised to ensure that access is equitable and sustainable. Implemented at scale, PrEP could be a game changer for HIV prevention globally, especially in high-burden countries.
Contribution: This study contributes by synthesising evidence on global PrEP guideline implementation, highlighting health system, structural, and societal challenges.
Keywords: PrEP; HIV; healthcare provider; HIV prevention; processes; challenges.
Introduction
Africa has made notable progress in HIV testing and treatment. However, primary prevention remains inadequate, underscoring the need to scale up effective strategies such as oral pre-exposure prophylaxis (PrEP), consistent condom use, and targeted behavioural interventions. In 2024, an estimated 1.3 million people were newly infected with HIV globally, with East, Southern, and West-Central Africa continuing to shoulder a substantial share of new infections (UNAIDS 2025). Despite significant progress in testing and treatment, prevention efforts in these regions remain inadequate as a result of persistent structural barriers, limited health system capacity, and stigma affecting key populations (Chimoyi et al. 2022). Underinvestment in prevention programmes and uneven integration of oral PrEP into national responses further constrain impact. To meet the Joint United Nations Programme on HIV and AIDS (UNAIDS) goal of fewer than 200 000 new annual HIV infections globally by 2030 necessitates a significant decrease in new infections (UNAIDS 2025). The expansion of established HIV-prevention strategies, which include broad access to and utilisation of oral PrEP, enhancement of health systems, and the resolution of social and structural obstacles that impede effective implementation, plays an important role in achieving this goal.
Daily oral HIV PrEP serves as a biological preventive intervention for individuals at heightened risk of HIV acquisition. In 2023, over 3.5 million individuals accessed PrEP at least once. More than 75% of this population, totalling 2.6 million, resided in the African region (UNAIDS 2024). The increase in individuals receiving PrEP by 35% from 2022 to 2023 remains insufficient, as the figures fall short of the goal of 10 million users by 2025. Inadequate adoption of PrEP is indicative of a multifaceted array of barriers functioning across various levels. At the individual level, limited awareness, perceived stigma, and concerns regarding side effects frequently restrict the willingness to initiate or adhere to PrEP. At the interpersonal level, insufficient partner support and apprehension regarding relationship conflict may hinder usage. At the community level, existing social norms, misinformation, and stigma regarding key populations diminish demand and acceptance.
At the structural level, national policies concerning PrEP prioritisation have profound implications for availability, accessibility, and service delivery models. Different implementation approaches have been adopted across countries, reflecting variations in epidemiological profiles, health system capacity, and government structures. South Africa’s national PrEP programme illustrates this approach through integration into primary healthcare, nurse-led initiation, and alignment with the Universal Test and Treat strategy, enabling scale-up via routine service platforms (Eakle et al. 2019; National Department of Health [NDoH] 2023). Similarly, Kenya, one of Africa’s earliest adopters, achieved rapid PrEP expansion through differentiated delivery models, strong NGO partnerships, targeted key population clinics, and substantial national training investments (Irungu & Baeten 2020; Ministry of Health Kenya 2022). In contrast, the United States employs a decentralised, insurance-based model supported by federal initiatives such as Ready, Set, PrEP, and community-based dispensing to broaden access (CDC 2021; Siegler et al. 2021). Collectively, these examples demonstrate how national policies, resources, and health system structures shape context-specific PrEP delivery pathways globally.
In 2012, the World Health Organization (WHO) initially recommended PrEP for specific population groups such as female sex workers, men who have sex with men, people who inject drugs, transgender people, people in prisons, and HIV-serodiscordant couples (Sullivan et al. 2019). Then, in 2015, the WHO recommended the use of PrEP for individuals with a substantial risk of contracting HIV. Following the WHO’s endorsement of PrEP, South Africa and other African countries implemented this HIV-preventive strategy beginning in 2016. In 2022, WHO guidance was amended to advocate a client-centred approach that considers individual choice, local contextual circumstances, individual behaviours, and partner traits when assessing who may benefit from PrEP (WHO 2022a).
Several African nations, including Zimbabwe, Zambia, Kenya, Uganda, Nigeria, and Ghana, have implemented oral PrEP programmes through their national public health systems, each employing distinct strategies. Kenya and Zimbabwe have incorporated PrEP delivery into HIV treatment and reproductive health services. Zambia has emphasised community-based PrEP distribution, whereas Ghana and Nigeria are enhancing PrEP access, using demonstration projects aimed at key populations (WHO 2022b). These countries have implemented ambitious national plans to deliver oral PrEP as part of their overall package of HIV-prevention services, with the aim of both decreased new HIV infections and long-term public health benefits. The utilisation of oral PrEP varies globally, significantly shaped by factors including national HIV prevalence, health system capacity, funding availability, policy priorities, community awareness, and stigma levels. Most countries have adopted comparable strategies regarding guidelines and service delivery models to facilitate effective implementation (UNAIDS 2023; WHO 2022a).
Aim of the study
This study analyses the global implementation processes aiming to better understand international variations in the implementation of PrEP guidelines and the challenges encountered at each stage, especially considering developing global directives and competing goals. Using this evidence is crucial to informing future work on how to improve the delivery of PrEP and accelerate progress towards global HIV-prevention goals.
Research methods and design
An integrative review design was selected as it facilitates the inclusion and synthesis of various empirical evidence, encompassing qualitative, quantitative, and mixed-methods studies, to produce a comprehensive understanding of the processes and challenges associated with global PrEP guideline implementation (Whittemore & Knafl 2005). The integrative approach differs from systematic or scoping reviews by embracing methodological diversity, making the approach especially appropriate for complex public health issues that encompass policy, health systems, and behavioural aspects. This design facilitated the synthesis of evidence from various contexts to guide future implementation strategies.
Stage 1: Problem identification
This review was guided by the research question: what are the processes and challenges involved in the global implementation of PrEP guidelines? The question was formulated to ensure clarity and relevance, using the Population, Intervention, Comparison, Outcomes (PICO) framework (eds. Higgins & Green 2013). The Population (P) comprised healthcare providers implementing PrEP guidelines globally and PrEP users. The Intervention (I) focused on the application of national PrEP guidelines, delivery models, strategies, and operational processes for integrating PrEP into routine services. A formal Comparison (C) was not applicable, as the review synthesised qualitative evidence rather than comparing interventions, although implementation differences across health systems were examined. The Outcomes (O) included the identification of implementation processes, facilitators, barriers, and broader system-level challenges.
Stage 2: Literature search
A literature search was performed between January and June 2025 on PubMed, Medline, EBSCOhost, CINAHL, and Google Scholar. To perform the search, the strategy used the following Boolean operators and used key terms: (‘pre-exposure prophylaxis’ OR ‘PrEP’) AND (‘implementation’ OR ‘processes’ OR ‘delivery’ OR ‘scale-up’) AND (‘barriers’ OR ‘challenges’ OR ‘facilitators’ OR ‘strategies’). Synonyms and related terms were identified by using Medical Subject Headings. We included studies published from 2019 to 2025 to capture recent evidence following the WHO’s 2016 recommendation to scale up PrEP and the subsequent development of national implementation models. The grey literature was not included in this review, and the review is restricted to peer-reviewed empirical studies for methodological rigour. Moreover, ancestry was conducted by using backward and forward citation tracking to identify additional eligible studies.
Stage 3: Data evaluation
After searching for eligibility, 111 full-text articles were assessed for inclusion, of which 102 were excluded as not meeting the inclusion criteria. the study selection process is illustrated in figure 1. Despite the numerous quantitative and mixed-methods studies identified and appraised by using quantitative critical appraisal checklists (Joanna Briggs Institute 2017), none met the inclusion requirements in the final synthesis, so no quantitative quality appraisal was carried out. All included studies were qualitative and assessed by the Qualitative Assessment and Review Instrument (QARI) checklist (Joanna Briggs Institute 2017). The nine studies that met the inclusion criteria obtained QARI scores ranging from 6 to 8 out of 10, reflecting aim clarity, methodological rigour, data collection adequacy, participant representation, depth analysis, credibility, and ethical issues. For methodological transparency and quality assurance, a rigorous QARI appraisal is covered in Table 1.
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FIGURE 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study selection. |
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| TABLE 1: Critical appraisal of included studies across methodological domains using JBI-Qualitative Assessment and Review Instrument. |
Stage 4: Data analysis
Thematic synthesis was conducted in accordance with the framework established by Whittemore and Knafl (2005). Data from eligible studies were compiled into a summary matrix that includes study design, population, setting, processes, challenges, and recommendations. The inductive thematic analysis was performed in four stages: identification of main findings through data reduction, tabulation of extracted data for data display, comparative analysis of data across studies, drawing of conclusions, and verification of themes. Themes were systematically refined through iterative review by all authors until a consensus was achieved, culminating in five overarching themes and their corresponding sub-themes, as detailed in Table 3.
Stage 5: Presentation of findings
The findings are organised thematically to demonstrate patterns and variations in the implementation of PrEP across various health system contexts. The final synthesis combines descriptive insights regarding processes with analytical insights concerning barriers and facilitators to guide future programme and policy development.
Ethical considerations
This study was approved by Sefako Makgatho Health Science University Research Ethics Committee (SMUREC) (No. SMUREC/H/485/2023: PG). The review did not involve any participants; thus, informed consent was not obtained. The study was conducted in accordance with the principles of honesty and transparency in the application of the methodology’s phases and accurate data reporting as outlined by Prager et al. (2019).
Results
Study demographics
Of the nine articles included, seven reported data from a total of 338 participants, comprising mainly nurse clinicians, counsellors, pharmacists, physicians, and expert clients (Table 2), and two did not specify the exact number of participants. All studies employed a qualitative research approach and were conducted in Australia (1), Belgium (1), Eswatini (1), Kenya (4), South Africa (1), and Zimbabwe (1).
| TABLE 2: A summary of included studies: Analysis of processes and challenges in the implementation of pre-exposure prophylaxis guidelines globally. |
Thematic findings on global pre-exposure prophylaxis guideline implementation processes and challenges
A global review of pre-exposure prophylaxis guideline implementation processes and challenges
The analysis yielded five main themes on the global review of PrEP guideline implementation processes and challenges, namely, Provider Perspectives and Implementation Processes, Client-Level Barriers and Sociocultural Factors, Health System and Structural Challenges, Facilitators and Adaptive Strategies, and Contextual and Comparative Insights (Table 3).
| TABLE 3: Identified themes and sub-themes. |
The results of this integrative review are summarised in Table 4, which outlines the main findings, associated challenges, and key facilitators identified across the reviewed studies. A detailed narrative description of each theme follows.
| TABLE 4: A summary of study’s main findings on global pre-exposure prophylaxis guideline implementation. |
Theme 1: Provider perspectives and implementation processes
The experience of providers and the processes of implementation appeared to be predominant across studies. The findings pertained to training adequacy, job clarity, task delegation, and counselling capability. This theme was reported in seven of the nine included studies and included the studies from Eswatini, Kenya, South Africa, Belgium, and Australia (Barnighausen et al. 2025; Baron et al. 2024; Gombe et al. 2024; Hicks et al. 2023; Nakambale et al. 2023; Smith et al. 2024; Vanhamel et al. 2023). The results are organised according to the following sub-themes:
Sub-theme 1.1: Initial enthusiasm, evolving concerns, and training gaps
Several studies highlighted in the study demonstrated an initial enthusiasm for PrEP by healthcare professionals (Barnighausen et al. 2025; Hicks et al. 2023). This study highlights the leading intention of providers to initiate PrEP as a statistically effective, biomedical HIV-prevention option. With time, several issues arose in relation to PrEP integration into routine service delivery. Concerns of decreased condom use and expanded unplanned pregnancies seem to stem from inadvertent behaviour changes, which is also known as risk compensation, in which people feel safer and adapt their sexual behaviour as a result. These findings are not necessarily the result of PrEP itself but rather reflect the wider shift in risk perception related to PrEP uptake. Additionally, concerns were expressed regarding the potential development of drug-resistant viral strains as a result of inconsistent adherence or incomplete implementation of PrEP protocols, reflecting patterns observed in previous HIV treatment trials. The evolving concerns underscore the need for continued training, support, and provider-optimisable evidence-based methods to maintain provider confidence for future PrEP rollout.
The review found several studies that highlighted continued provider training and clinical deficits in PrEP service delivery (Baron et al. 2024; Gombe et al. 2024). This study noted that insufficient skills in counselling, poor knowledge of PrEP dosing protocols, and uncertainty about how to manage side effects were all critical factors that reduced the quality of service delivery. The limitations diminished provider confidence and undermined effective client engagement. Thus, ongoing training, clinical mentorship, and supportive supervision are essential to enhance provider capacity and ensure the delivery of consistent, high-quality PrEP counselling and management.
Sub-theme 1.2: Task-shifting and role expansion
A review of articles tracing the scale-up of PrEP services utilised task-shifting approaches in varied settings (Hicks et al. 2023; Nakambale et al. 2023; Vanhamel et al. 2023). Our results from this review demonstrate that task-shifting PrEP delivery to nurses, lay counsellors, and pharmacy workers increased service availability and addressed clinical bottlenecks. Initiation of PrEP was both triggered and facilitated by healthcare workers offering counselling and adherence support, particularly in resource-poor or highly utilised settings. While these results are encouraging, regulatory and policy barriers emerged as common impediments to full implementation and scale-up of task-shifting.
Sub-theme 1.3: Policy and regulatory barriers
This review underscores that regulatory frameworks and policy misalignment features of regulatory architecture are fundamental implementation bottlenecks for PrEP scale-up in varied contexts (Smith et al. 2024; Vanhamel et al. 2023). The results indicate that variations in the scope of practice and prescribing authority significantly impacted the rollout of PrEP. Constraints on prescribing in various settings have restricted qualified personnel, including STI nurses, medical assistants, and harm reduction staff, from initiating PrEP, consequently limiting service access. Organisation-neutral reimbursement policies and funding mechanisms frequently do not cover PrEP services provided outside conventional clinical settings, resulting in financial disincentives for providers and limiting service expansion (Killelea et al. 2022). These structural barriers marginalised the complexity of innovative and restrained uptake of PrEP through non-traditional care models such as pharmacy or community-based mode. A prominent point that kept cropping up was the need for legislative change and delivery systems that are more inclusive and adaptable in terms of bringing PrEP at scale to priority groups.
Sub-theme 1.4: Implementation workflow challenges
These included articles indicate that prolonged initiation processes and structural barriers prevented the implementation of PrEP (Nakambale et al. 2023; Barnighausen et al. 2025). The findings of this review also indicate that implementation problems within the workflows affected not only the health service providers but also the clients, often leading to significant delays and frustrations as well as a reduction in service uptake. There was a consensus among providers that documentation increased the burden on their already strained system and implemented very rigid protocols, which led to longer waiting times and many visits for clients. The study results illuminate the importance of streamlining PrEP onboarding steps and operations to better deliver services, improve client satisfaction, and support wider uptake.
Theme 2: Client-level barriers and sociocultural factors
This review identified client-level barriers and sociocultural factors that influence PrEP uptake and adherence across several studies. Evidence for this theme came from five studies conducted in Kenya, Zimbabwe, Eswatini, and South Africa (Atkins et al. 2022; Baron et al. 2024; Barnighausen et al. 2025; Gombe et al. 2024; Nakambale et al. 2023). Below are the sub-themes that address these challenges.
Sub-theme 2.1: Stigma and misconceptions
Two studies that are included in this review underlined stigma as one of the main reasons for a lack of PrEP initiation and non-adherence (Atkins et al. 2022; Gombe et al. 2024). Findings from this review suggest that many clients were concerned with being associated with taking PrEP pills that appeared like antiretroviral therapy, accessing PrEP service, being labelled as having HIV, or being seen as sexually promiscuous. The stigma had been largely perpetuated by persistent, community-wide misconceptions about PrEP: both what it was developed to do and for whom. These dynamics created barriers to uptake, discouraged potential adopters, and adversely impacted adherence. The literature reviewed identifies the need for broad, locally developed, PrEP-normative communication campaigns to counteract misconceptions.
Sub-theme 2.2: Communication barriers between clients and providers
The study included in this review showed client discomfort in discussing sexual behaviours with healthcare providers, particularly within the pharmacy-based PrEP delivery models (Nakambale et al. 2023). This finding is in keeping with the observation that a lack of eagerness on the part of providers to discuss openly constrained complete risk evaluation and counselling. The lack of communication compromised providers’ capacity to personalise PrEP communication and adherence support. Client-centred communication enhancements to support discretion, neutrality, and cultural competency may improve the quality of PrEP services.
Sub-theme 2.3: Gender and power dynamics
The review also found studies that demonstrate that sociocultural norms – in particular, patriarchal norms – influence PrEP acceptability and use in women (Barnighausen et al. 2025; Baron et al. 2024). Results suggest that PrEP acceptability and continuation were often undermined by a lack of willingness of male partners to support women’s autonomy and control in HIV-prevention decisions. This context constrained women’s capacity to utilise PrEP effectively as an HIV-prevention tool. The literature review underscores the importance of designing and implementing interventions that actively involve male partners, as their support is essential in influencing women’s decisions and autonomy in HIV prevention. Enhancing male partner involvement in conjunction with women’s empowerment can create supportive environments that diminish relational barriers, improve PrEP acceptability, and encourage sustained use among at-risk women.
Sub-theme 2.4: Financial barriers
Two studies included in this review mentioned that financial costs associated with PrEP provision, such as charges at pharmacy-based delivery models and poor insurance reimbursement, presented major hindrances to client access (Nakambale et al. 2023; Smith et al. 2024). This review demonstrates the importance of cost in achieving equity in PrEP delivery. Interventions addressing economic barriers, including the removal of user fees, provision of transport subsidies, insurance coverage for PrEP services, and the integration of PrEP into existing publicly funded programmes, are critical elements of comprehensive HIV-prevention strategies. These strategies may decrease out-of-pocket expenses, enhance equitable access, and facilitate sustained engagement among economically disadvantaged and high-risk groups.
Theme 3: Health system and structural challenges
Multiple studies in this review highlighted health system and structural obstacles to PrEP adoption. Five studies contributed to this theme, including those from Kenya, South Africa, Belgium, and Eswatini (Baron et al. 2024; Hicks et al. 2023; Irungu et al. 2021; Nakambale et al. 2023; Vanhamel et al. 2023). Below are the sub-themes that speak to these challenges.
Sub-theme 3.1: Fragmented planning and communication
The review identified that fragmentation in programme design, characterised by misaligned implementation frameworks, overlapping partner activities, and ambiguous role delineation between government and implementing agencies, obstructed coordinated PrEP delivery. Inadequate communication among national authorities, clinics, and implementing partners resulted in inconsistent policy interpretation, duplication of reporting systems, delayed feedback loops, and fragmented data sharing. These issues undermined timely decision-making and the cohesive scale-up of PrEP services (Baron et al. 2024; Irungu et al. 2021). The findings indicate that conflicting priorities and ambiguous targets among stakeholders hindered coordinated efforts, obstructing the development of cohesive and sustainable PrEP programmes.
Sub-theme 3.2: Resource shortages
This review identified that the ongoing stockouts of critical resources, such as PrEP drugs, test kits, and stationery, affect service continuity, particularly in rural clinics (Baron et al. 2024; Hicks et al. 2023). These results suggest that the resources that are reportedly inadequate to meet the high demand for service interruptions reduce the trust of patients in PrEP services. Efficient supply chains and sufficient resources are essential for reliable processes managing continuous use of and adherence to PrEP among users.
Sub-theme 3.3: Workload and capacity constraints
Three articles in this review found that large volumes of patients coupled with inadequate staffing resulted in excessive workloads for healthcare workers (Irungu et al. 2021; Nakambale et al. 2023; Vanhamel et al. 2023). These pressures, identified as key influences on primary resources for PrEP providers, signal the resultant and decreased time available to undertake important activities such as brief adherence interviews, care engagement activities, or ensured delivery of meaningful client-centred counselling. The need for workforce enhancement and resource allocation becomes more urgent to ensure continuity of PrEP programmes as a result of burnout or loss of staff in the health systems.
Sub-theme 3.4: Monitoring and data systems
This review found an article that highlighted the continued deficiencies in monitoring and data management systems, which obfuscate effective oversight of overall programmes and guidance by data (Baron et al. 2024). The findings underscore the critical need for strengthening surveillance and evaluation frameworks to enable timely adaptations and improvements in PrEP service delivery. Robust data systems can facilitate accurate tracking of client outcomes, stock management, and service coverage, which are essential for responsive and sustainable programme implementation. Better performing these systems will also enable better policy decisions and resource allocation to address new challenges in the PrEP implementation scale-up.
Theme 4: Facilitators and adaptive strategies
Several of the included studies emphasised facilitators and adaptive strategies for enhancing PrEP implementation. These strategies focused on strengthening service delivery through task-shifting, community engagement, simplified procedures, and client-centred innovations. Facilitators and strategies were described in six studies, particularly those from Kenya, Belgium, Eswatini, and South Africa (Barnighausen et al. 2025; Baron et al. 2024; Gombe et al. 2024; Hicks et al. 2023; Nakambale et al. 2023; Vanhamel et al. 2023). The pertinent findings are explored under the following sub-themes.
Sub-theme 4.1: Task-shifting and multidisciplinary collaboration
This review identified articles documenting the use of task-shifting as a strategy to expand PrEP service delivery (Hicks et al. 2023; Vanhamel et al. 2023). The findings highlight that adaptive service models combining task-shifting with collaboration among clinicians, nurses, counsellors, and community health workers can significantly improve service efficiency and client outcomes. By redistributing responsibilities, such as PrEP initiation and adherence support, to a broader range of health cadres, these models reduce bottlenecks in clinical settings and extend reach to underserved populations. Task-shifting also supports the sustainability of PrEP programmes by addressing workforce shortages and enhancing provider capacity. Successful implementation of these models necessitates clear role definitions, sufficient training, and supportive supervision to ensure service quality and maintain client trust.
Sub-theme 4.2: Simplification of procedures
The review found that simplifying service initiation and broadening eligibility criteria can promote PrEP uptake, improve client convenience, and eliminate barriers to care (Barnighausen et al. 2025; Baron et al. 2024). These findings indicate that simplified clinic procedures, for example, offering same-day initiation of PrEP and loosening eligibility criteria for clients are associated with earlier access and increased re-engagement with care. Streamlined processes facilitate service delivery for providers and decrease client waiting times (Bonett et al. 2024). These efficiencies reduce frustration and enhance overall satisfaction among PrEP users. Furthermore, implementing flexible eligibility criteria that consider individual risk profiles, instead of strict categorical qualifications, improves inclusivity and guarantees that high-risk populations retain access. This approach is particularly important for resource-poor settings, in which the constraint on resources as a result of human-resource limits necessitates streamlining the delivery of services to increase the effectiveness of programmes.
Sub-theme 4.3: Community engagement and stigma reduction
This review highlights a study that shows the involvement of community leaders and male partners, along with culturally relevant educational initiatives, significantly decreased stigma and enhanced community acceptance of PrEP (Gombe et al. 2024). The findings underscore the significance of engaging key community leaders and customising communication to align with local cultural contexts to promote supportive environments for PrEP adoption. These approaches effectively address misconceptions, normalise PrEP usage, and promote ongoing adherence within target populations.
Sub-theme 4.4: Client-centred innovations
This review identified studies that highlight innovations, including self-screening tools, flexible scheduling options, and the decentralisation of service delivery via pharmacies and telehealth platforms, as effective strategies for addressing client preferences and enhancing PrEP access (Nakambale et al. 2023). These client-centred approaches reduce barriers related to convenience and privacy, thereby fostering greater uptake and adherence. By aligning service delivery with user needs, these innovations contribute to more responsive and accessible PrEP programmes.
Sub-theme 4.5: Ongoing training and support
This review highlights studies that emphasise the need for continuous capacity building and refresher providers’ skills as well as quality of PrEP services (Hicks et al. 2023). The findings imply that in-service refresher training and continued supportive supervision are significant to ensure that healthcare providers are equipped with the necessary information, such as guidelines to improve their counselling skills. Continuous education bolsters PrEP provision trust and ensures consistent, good-quality PrEP delivery.
Theme 5: Contextual and comparative insights
This review synthesised findings from extensive research to identify contextual and comparative insights. The findings signify the influences of different legal issues, economic statuses, and sociocultural factors on the implementation of PrEP programmes. Differences between high-income and low- to middle-income countries affected factors including task-shifting, affordability, policy support, and community engagement. Cross-context insights were drawn from seven studies conducted across high-income and low-income settings, including Australia, Belgium, Kenya, South Africa, and Eswatini (Barnighausen et al. 2025; Baron et al. 2024; Gombe et al. 2024; Hicks et al. 2023; Nakambale et al. 2023; Smith et al. 2024; Vanhamel et al. 2023). The theme is analysed through the following sub-themes.
Sub-theme 5.1: Variation between settings
The reviewed articles published previously have shown the variation in different contexts of implementation related to high-income, as well as low-income countries (Barnighausen et al. 2025; Smith et al. 2024; Vanhamel et al. 2023). This research shows that regulatory inflexibility and a narrow scope of practice provide substantial obstacles in developed settings, often limiting provider roles and service breadth. Economic, supply chain, and sociocultural determinants such as stigma and gender norms continue to challenge PrEP introduction into African contexts. Understanding these multiple barriers is important for tailoring interventions tailored to suit the needs of diverse contexts and promote global PrEP equity.
Sub-theme 5.2: Financial and policy contexts
This review underscores the economic practicality and the regional variation shaping access to, affordability of, and integration of PrEP within health systems (Nakambale et al. 2023; Smith et al. 2024). The results show that changes in funds as mechanisms, insurance coverage, and reimbursement policies create differences in the availability of services and client engagement. Wider economic and policy issues aside, context-specific funding options are needed to ensure that access to PrEP is equitable, especially for populations that are marginalised or most at risk. In different settings, their bespoke approaches will be essential to overcome the financial challenge and realise sustainable programmatic coverage.
Sub-theme 5.3: Adaptability and sustainability considerations
This review identified studies that reinforce consistent messages on the need to synergise national policies with local innovations for the sustainable scale-up of PrEP services (Baron et al. 2024). The findings underscore the necessity of facilitating flexible and context-specific delivery models while maintaining a continuous supply of financial, human, and material resources. This alignment underpins programme resilience, responsiveness to community needs, and the future iteration for PrEP integration into existing health systems. A lack of attention to these factors is likely to be the reason equitable and sustainable PrEP access is so difficult to achieve.
Discussion
This integrative study explored the global view of the implementation of PrEP. The results reveal continuous challenges together with adaptation strategies necessary for wider scalability and sustainability in diverse settings.
Provider dynamics and implementation processes
Healthcare providers are essential to the successful adoption of PrEP. Research conducted in South Africa, Kenya, and Eswatini indicates that initial enthusiasm among providers was mitigated by insufficient training, changing clinical issues, and increased administrative responsibilities (Barnighausen et al. 2025; Baron et al. 2024; Hicks et al. 2023). Providers consistently highlighted insufficient counselling skills, uncertainty regarding PrEP dosing, and a lack of confidence in managing side effects, all of which impacted service quality (Baron et al. 2024; Gombe et al. 2024). The findings corroborate existing global evidence indicating that continuous mentorship and standardised training are crucial for maintaining quality and enhancing provider confidence in PrEP service delivery.
Task-shifting has become a prevalent strategy in various contexts, such as Kenya, Belgium, and Eswatini (Hicks et al. 2023; Nakambale et al. 2023; Vanhamel et al. 2023). The delegation of responsibilities to nurses, chemists, and lay counsellors enhanced service accessibility and alleviated bottlenecks, aligning with the WHO’s focus on differentiated service delivery. Several studies have identified regulatory and reimbursement constraints that limit the prescribing authority of nurses and chemists (Smith et al. 2024; Vanhamel et al. 2023). This regulatory rigidity highlights the necessity for legislative flexibility to institutionalise task-shifting and improve PrEP accessibility.
Client barriers and sociocultural contexts
Stigma, gender norms, and misinformation were identified as significant barriers to PrEP uptake and adherence (Atkins et al. 2022; Gombe et al. 2024). In Kenya and Zimbabwe, the stigma associated with being labelled as HIV-positive or sexually promiscuous deterred clients from starting or maintaining PrEP (Gombe et al. 2024). Pharmacy-based models have shown that discomfort in discussing sexual behaviour with providers negatively impacts adherence and personalised counselling (Nakambale et al. 2023). The observations underscore the significance of privacy protection, culturally competent communication, and stigma-sensitive service environments.
Gendered power dynamics significantly limited women’s utilisation of PrEP, as male partners frequently opposed or dissuaded women’s engagement in prevention initiatives (Barnighausen et al. 2025; Baron et al. 2024). In alignment with research conducted in Kenya and South Africa, the engagement of men and the challenge of patriarchal norms are essential strategies for enhancing women’s autonomy and ensuring sustained PrEP utilisation. Economic barriers, including user fees in private pharmacies and insufficient insurance coverage, were observed in both high- and low-income contexts (Nakambale et al. 2023; Smith et al. 2024). Addressing affordability via subsidies or incorporating into public health systems is essential for ensuring equitable access.
Health system and structural factors
System-level barriers, such as fragmented planning, resource shortages, and inadequate monitoring systems, were identified in various studies (Baron et al. 2024; Irungu et al. 2021). Inadequate coordination among ministries, clinics, and implementing partners resulted in inconsistent data reporting, delayed feedback, and inefficiencies in the scale-up of PrEP (Baron et al. 2024). Frequent medication stockouts and insufficient staffing in rural facilities compromised service continuity (Baron et al. 2024; Hicks et al. 2023). Workforce shortages and administrative burdens similarly diminished providers’ capacity to deliver high-quality counselling (Nakambale et al. 2023; Vanhamel et al. 2023). The findings indicate that effective scale-up relies on robust supply chains, sufficient human resources, and operational data systems.
Facilitators and innovations promoting pre-exposure prophylaxis uptake and delivery
Multiple adaptive strategies enabled efficient PrEP delivery. Research conducted in Kenya, Belgium, and Eswatini indicates that task-shifting and multidisciplinary collaboration enhance efficiency and broaden reach (Barnighausen et al. 2025; Hicks et al. 2023; Vanhamel et al. 2023). Simplifying procedures, including same-day initiation, reduced eligibility restrictions, and multi-month dispensing, has improved convenience and retention (Barnighausen et al. 2025; Baron et al. 2024). Interventions for community engagement that include local leaders and male partners have been effective in normalising PrEP use and reducing stigma (Gombe et al. 2024). Client-centred innovations, including self-screening tools, flexible scheduling, and pharmacy-based delivery models, have enhanced privacy and accessibility (Nakambale et al. 2023). Ongoing provider training and mentorship are essential for maintaining quality and programme fidelity (Hicks et al. 2023).
Contextual and comparative insights
Comparative analyses across contexts indicated that the capacity of health systems, the structures of financing, and the flexibility of policies influence the outcomes of PrEP implementation. Research conducted in high-income contexts such as Belgium and Australia has highlighted restrictive reimbursement policies and constrained nurse prescribing rights (Smith et al. 2024; Vanhamel et al. 2023). Conversely, in sub-Saharan Africa, barriers arise from resource limitations, fragmented governance, and sociocultural resistance (Baron et al. 2024; Hicks et al. 2023). Research from Kenya and Eswatini indicates that decentralised models and community engagement may mitigate these barriers (Barnighausen et al. 2025; Nakambale et al. 2023). The findings highlight the necessity of context-sensitive policy frameworks that reconcile international standards with local adaptability to ensure the global scale-up of PrEP.
Results summary
The results of this review confirm international trends regarding the operational and contextual difficulties in the uptake of PrEP by various health systems. Gaps in training, limited confidence among providers, and fragmented implementation processes are identified in Kenya, Zimbabwe, and Eswatini studies that obstruct regular PrEP implementation and scale-up (Atkins et al. 2022; Barnighausen et al. 2025; Gombe et al. 2024). Evidence from high-income settings such as Belgium and Australia consistently suggests structural obstacles, including workflow inefficiencies, the burden of documentation, and limited PrEP integration within routine clinical practice (Smith et al. 2024; Vanhamel et al. 2023). In line with this review, international literature highlights the role of sociocultural and behavioural considerations such as stigma, gender dynamics, perceptions of PrEP efficacy, and concerns about risk compensation in uptake and continuation. The facilitators highlighted from this synthesis, including task-shifting, simplified initiation protocols, community engagement, and collaborative partnerships, are generalisable enablers of successful PrEP implementation globally.
The global scale-up of PrEP is making progress but has major barriers to overcome. Achieving its impact on prevention must involve addressing structural, financial, and social constraints while strengthening training, learning, and outreach. Collaborative approaches that use local resources, innovative delivery models, and supportive policies are essential to equitable and sustainable implementation. While PrEP has proven to be an intervention, its potential will go unfulfilled unless action is coordinated and decisive. By addressing systemic inequities, centring affected communities, and scaling adaptive approaches, HIV transmission can be further reduced, enabling high-burden countries to move closer to an HIV-free generation.
Limitations and future research
The PrEP guidelines in several countries differ and are widely influenced by the practice pattern, such as healthcare infrastructure, fund availability, and sociocultural factors. This diversity restricts the applicability of the findings to varied settings. Additionally, consider the effects of enabling policies, and more effectively direct resource allocation for the scale-up and sustainability of PrEP uptake.
Implications for policy and practice
Strengthening provider training and support
Providers receive ongoing training in delivery, supported by policies that mandate ongoing professional development to ensure timely, confident, and high-quality client engagement.
Simplify service delivery and eligibility criteria
Flexible initiation processes and risk-informed eligibility can reduce client and provider burdens. The policies should support the integration of PrEP into the existing sex and reproductive health services provided.
Addressing stigma and sociocultural barriers
Tailored strategies are needed to address gender barriers, including culturally informed education and engagement with community gatekeepers and male partners.
Enhancing resource allocation and health system strengthening
Effective PrEP care cascades require robust supply chains, an adequate workforce, and strong monitoring systems. Policymakers should prioritise infrastructure and data systems.
Increasing financial accessibility
Equitable access to PrEP requires policy frameworks that reduce financial barriers through subsidies or universal insurance coverage.
Foster context-sensitive implementation
Policies must be flexible for local adaptation, considering the diversity in regulatory frameworks, cultural practices, and health system performance in different regions.
Recommendations
For equitable and sustained implementation, a collaborative model that relies on local assets, new delivery models, and enabling policies is crucial. PrEP is a proven intervention, but its full impact will not materialise without audacious, coordinated action. If we tackle systemic inequities, place the affected communities at the centre, and continue scaling adaptive strategies, HIV transmission can be further curtailed, and high-burden countries will be closer to an HIV-free generation.
Conclusion
Scaling up the global implementation of PrEP guidelines reflects increased commitment to strengthening HIV prevention through policy adoption, health system integration and expanded service delivery models. Achieving the maximum preventive value of PrEP also requires tackling structural, financial, and social constraints while strengthening learning, training, and outreach.
Acknowledgements
The authors are indebted to Sefako Makgatho Health Science University for providing this opportunity to conduct research. The authors would like to acknowledge the contribution and insights of Prof. Deliwe R. Phetlhu and Dr Andile G. Mokoena-de Beer, the study supervisors.
Competing interests
The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.
CRediT authorship contribution
Junior M. Ntimani: Conceptualisation, Methodology, Writing – original draft, Writing – review & editing. Andile G. Mokoena-de Beer: Conceptualisation, Data curation, Supervision, Writing – review & editing. Deliwe R. Phetlhu: Data curation, Methodology, Supervision, Writing – review & editing. All authors reviewed the article, contributed to the discussion of results, approved the final version for submission and publication, and take responsibility for the integrity of its findings.
Funding information
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Data availability
All data supporting this review are derived from previously published studies, which are cited within the manuscript. No new data were generated.
Disclaimer
The views and opinions expressed in this article are those of the authors and are the product of professional research. They do not necessarily reflect the official policy or position of any affiliated institution, funder, agency, or that of the publisher. The authors are responsible for this article’s results, findings, and content.
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