There are many challenges to accessing PrEP and thus low uptake in the United States. This review (2007–2017) of PrEP implementation identified barriers to PrEP and interventions to match those barriers. The final set of articles (n = 47) included content on cognitive aspects of HIV service providers and individuals at risk for infection, reviews, and case studies. Cogni- tive barriers and interventions regarding patients and providers included knowledge, attitudes, and beliefs about PrEP. The “purview paradox” was identified as a key barrier—HIV specialists often do not see HIV-negative patients, while primary care physicians, who often see uninfected patients, are not trained to provide PrEP. Healthcare systems barriers included lack of communication about, funding for, and access to PrEP. The intersection between PrEP-stigma, HIV-stigma, transphobia, homophobia, and disparities across gender, racial, and ethnic groups were identified; but few interventions addressed these barriers. We recommend multilevel interventions targeting barriers at multiple socioecological domains. Keywords PrEP implementation · PrEP integrative review · HIV prevention · Continuum of care Resumen Existen muchos desafíos para acceder a PrEP y, por lo tanto, poca aceptación en los Estados Unidos. Esta revisión (2007- 17) de la implementación de PrEP identificó las barreras a la PrEP y las intervenciones para hacer coincidir esas barreras. El conjunto final de artículos (n = 47) incluyó contenido sobre los aspectos cognitivos de los proveedores de servicios de VIH y las personas en riesgo de infección, revisiones y estudios de casos. Las barreras cognitivas y las intervenciones con respecto a los pacientes y proveedores incluyeron el conocimiento, las actitudes y las creencias sobre la PrEP. La “purview paradox” se identificó como una barrera clave: los especialistas en VIH a menudo no ven pacientes VIH negativos, mientras que los médicos de atención primaria, que a menudo ven pacientes no infectados, no están capacitados para proporcionar PrEP. Las barreras de los sistemas de salud incluyen la falta de comunicación, financiación y acceso a la PrEP. Se identificó la intersección entre el estigma de la PrEP, el estigma del VIH, la transfobia, la homofobia y las disparidades entre los grupos de género, raciales y étnicos; pero pocas intervenciones abordaron estas barreras. Recomendamos intervenciones multinivel dirigidas a las barreras en múltiples dominios socioecológicos. Introduction In 2011–2012, the United States Centers for Disease Control * Rogério M. Pinto and Prevention (CDC) launched the high-impact HIV pre- firstname.lastname@example.org vention (HIP) approach to respond to research showing that School of Social Work, University of Michigan, Ann Arbor, antiretroviral therapy (ART) reduces HIV transmission by MI, USA lowering viral load in the bloodstream . In 2012, the use Sociology and Sexuality Studies, San Francisco State of ART emerged as the dominant strategy for HIV treatment University, San Francisco, CA, USA and prevention —research predicted reduction of sexual Department of Obstetrics and Gynecology, University transmission in HIV-serodiscordant couples by more than of Michigan Medical School, Ann Arbor, MI, USA 96% . High-impact interventions—HIV testing, linkage University of Michigan School of Social Work, Room 2850, to care, and HIV viral suppression with ART—constitute 1080 South University, Ann Arbor, MI 48109, USA Vol.:(0123456789) 1 3 AIDS and Behavior key steps of the HIV Continuum of Care, recommended by across the fields of medicine, nursing, social work, pub- the World Health Organization [4, 5]. HIP promotes HIV lic health, and the social sciences. Therefore, this review pre-exposure prophylaxis (PrEP). PrEP has been tradition- included papers in all these disciplines and sought to identify ally considered as once daily oral dosing of ART prescribed barriers to PrEP and the interventions available that spe- to individuals at risk for HIV infection. The Food and Drug cifically matched those barriers. We focused specifically Administration (FDA) approved Truvada™ [Emtricitabine/ on PrEP implementation in the US and on implementation Tenofovir Disoproxil Fumarate (TDF/FTC)] in 2012 as a issues faced by at-risk individuals and HIV service provid- PrEP strategy that reduced the risk of HIV acquisition by ers, the agency settings in which services are offered, and 73% among adult men who have sex with men (MSM) and the policies that guide HIV service provision. “HIV service transgender women who took it 90% of the time ; with providers” in this context refer to counselors, educators, case greater efficacy (up to 99%) for individuals with higher rates managers and others who provide HIV testing, linkage to of adherence and increased concentrations among serodis- care, and other services, as well as HIV-care providers. Our cordant heterosexual couples [7, 8]. review aims to improve HIV-prevention strategies nation- Herein, the steps patients and providers must take to wide by demonstrating how to confront identified barriers follow policies governing access to PrEP and to navigate with interventions that might improve access, uptake, and healthcare systems will be referred to as “PrEP implemen- adherence to PrEP. tation.” PrEP implementation may appear to be an easy and effective way to stop HIV transmission; however, there are many challenges to accessing and adhering to PrEP, as Methods reflected in low levels of PrEP uptake in the US [9 , 10]. Concern over rates of adherence and retention have been Literature Review Conceptual Approach reported in PrEP care in clinical trials and “real world” PrEP demonstration projects [11, 12]. Racial and gender dispari- The extant literature consistently suggests that to improve ties have also been identified, including disproportionately PrEP implementation, key barriers need to be overcome low PrEP uptake among Black MSM . Research regard- and interventions need to be developed at all levels (cli- ing low access, uptake, and adherence to PrEP in the US has ents/patients, HIP service providers, healthcare systems, focused mostly on breakdowns in the healthcare systems and policy) [17–19]. Therefore, our review follows a socio- implementing PrEP, lack of provider awareness and willing- ecological perspective  suggesting that barriers to PrEP ness to prescribe PrEP [9, 14], and unfavorable patient and implementation fall within four domains. The Individual and community attitudes about PrEP [15, 16]. Our aim therefore Relationships Domains represent patients and care provid- is to comprehensively review this literature, focusing on how ers, as well as the professional connections they establish barriers to PrEP uptake might affect both individual actors along the HIV Continuum of Care that may hinder or facili- and healthcare systems. tate PrEP implementation; barriers in this domain involve Barriers to PrEP implementation occur across gender, knowledge of, attitudes about, and burdens regarding PrEP racial, and ethnic groups. Various interventions have been implementation. The Community and Policy Domains rep- proposed to solve this public health problem, including those resent policies governing HIV-prevention efforts, including targeting different domains of prevention and care—patients, PrEP implementation across healthcare systems and agency providers, and healthcare systems. Nonetheless, proposed settings in communities where at-risk individuals access interventions to improve PrEP implementation may vary PrEP; barriers in this domain include structural factors in Fig. 1 Conceptual approach: socioecological barriers to PrEP implementation 1 3 AIDS and Behavior healthcare systems, and governmental and health-organi- patients specifically related to the effective implementa- zation guidelines that might hinder PrEP implementation. tion of PrEP. We also included studies focused on attitudes The socioecological perspective, summarized in Fig. 1 and beliefs of HIV-prevention providers. We restricted this (modified from Mugavero et al. 2013), is consistent with review to research in the US because of the unique historical ecological models in public health and epidemiology, from response to HIV/AIDS in the US and the particular attributes Bronfenbrenner’s ecological systems theory to more-recent of its healthcare system, and to yield results applicable to theories in social epidemiology . This approach focuses PrEP implementation in the US. on individuals within larger social environments (patients) and institutional environments (care providers); significantly, Procedures for Article Selection it distinguishes between interventions that target individu- als and their environmental and structural contexts. Our Figure 2 summarizes our procedures for article selection. approach to PrEP implementation acknowledges that both Our initial search yielded 294 articles. Following our inclu- individuals and their healthcare providers are embedded sion criteria, we first read titles and abstracts and screened within larger healthcare systems governed by multiple poli- out 227 papers that did not match our criteria. For exam- cies [22, 23]. ple, in this screening we excluded articles focusing on PrEP implementation outside the US and papers exclusively Integrative Review Model addressing attitudes and beliefs of individuals (e.g., PrEP acceptability studies)—yielding 67 articles, which were We adopted an integrative review model to provide a more fully assessed. As we read and discussed the articles, we comprehensive understanding of PrEP implementation in screened out another 20 whose contributions lacked rele- various domains of reference . Our review focuses on a vance to the study of PrEP implementation (e.g., editorials period (January 2007 to June 2017) that included the emer- on the promise of PrEP alone, studies of public support, gence of the concept of the HIV Continuum of Care and the and cost-effectiveness studies), bringing our final sample to high-impact prevention (HIP) approach, followed by large- 47 articles. To organize and manage our library, we created scale clinical trials (e.g., the iPrEx study) [6, 25, 26], and an Excel spreadsheet to record key information about each the subsequent approval by the FDA (in July 2012) of the publication: title, authors, journal, publication date, journal provision of PrEP in service settings . type, methods and methodology, and a summary of findings. Literature Search Terms Analysis We used combinations of search terms in ArticlesPlus, a Our analysis focused on identifying barriers to PrEP and the comprehensive database of peer-reviewed clinical and aca- interventions aligned with those barriers. To enhance the demic journals in medicine, public health, social work, nurs- rigor of our analysis, we adopted the following techniques: ing, pharmacy, and law, hosted by the University of Michi- purposive sampling; grounded theory; and multidisciplinary gan Library. Our combination of search terms, including collaborative interpretation . truncation operators (*), was as follows: Subject Terms: (HIV OR HIV/AIDS OR AIDS) AND Purposive Sampling Title: (PrEP OR “Pre-Exposure Prophylaxis”) OR [(antiretroviral* OR pharmaceutical*) AND prevent*)] AND We borrow the term “purposive sampling” to describe the All Fields: [(worker* OR practitioner* OR provider*) procedures we used (described above) to select the articles AND (linkage* OR linking OR referral* OR implementa- for this integrative review—specific search terms, inclusion tion OR uptake)] and exclusion selection criteria, and procedures for article selection. Inclusion and Exclusion Criteria We included peer-reviewed papers presenting research on Grounded Theory PrEP implementation, PrEP in the US, HIV service work- ers, practitioners, medical or social-service providers, and Our analysis reflects a modified version of grounded theory service agencies. We excluded papers that exclusively  in which how we selected the final set of articles for addressed the attitudes and beliefs of individuals targeted analysis, as well as how we read/interpreted the articles, was by HIV-prevention programs; however, we did include stud- based on the content we found and grounded in our experi- ies focused on the attitudes and beliefs of potential PrEP ences as both HIV/AIDS researchers and practitioners in 1 3 AIDS and Behavior Identified articles through database search (n=294) Inclusion Criteria: (1) Implementation of PrEP programs for HIV prevention (2) Focus on PrEP implementation in the US (3) Focus on HIV service providers and medical and social- service providers in agency settings Excluded articles: n=227 Screened articles for full-text assessment for inclusion in review Exclusion Criteria: (n=67) (1) Focus on PrEP implementation outside the US (n=4) (2) Retrospective chart reviews without relevant contribution to study (n=1) (3) Summaries of PrEP clinical guidelines or efficacy trials alone (n=5) (4) Editorials without implementation content (n=8) Final articles selected (5) Focus on public support for PrEP (n=1) for inclusion in review (6) Cost-effectiveness study (n=1) Excludedarticles: n=20 (n=47) Fig. 2 Summary of article selection and inclusion and exclusion criteria community settings offering HIV-related services. We con- interpretation. Based on our shared interpretation and judg- curred on definitions, recurring terms, and barriers and solu- ment, we organized a pragmatic list (Table 1). tions to PrEP implementation before beginning analysis. We also used a conceptual framework to guide how we identi- fied and aligned barriers with interventions in the selected Results articles. The final set of articles (n = 47) included four broad cat- Multidisciplinary Collaborative Interpretation egories of papers: primary data on cognitive variables (e.g., perspectives, beliefs, and concerns) of HIV-prevention pro- The examination of the 47 selected articles included a full- viders (n = 18) [9, 14, 30–45]; primary data on cognitive var- text reading of each paper. The list of articles was ordered by iables and perspectives of individuals considered at risk for relevance to our search terms and this order was maintained HIV infection (n = 9) [46–54]; reviews of current literature throughout the review. Articles were discussed by the first on PrEP implementation (n = 16) [10, 11, 17, 19, 55–66]; two authors, with expertise in social work and anthropol- and case studies of PrEP demonstration and implementation ogy, grounded in the conceptual foundation above. Given the projects (n = 4) [12, 54, 67, 68]. From the text of these arti- close connections across barriers and interventions regard- cles, we extracted and recorded key barriers to implementa- ing patients and providers, we combined them under the tion and the interventions proposed to address them. Then “Individual and Relationships Domains.” Since healthcare we mapped out the barriers. Among patients and providers, systems operate within communities and are concurrently we identified cognitive barriers and interventions regarding influenced by myriad policies, we combined healthcare-sys- their knowledge, attitudes, and beliefs about PrEP. Barriers tem barriers and interventions under “Community and Pol- involving healthcare systems included communication and icy Domains.” To address researcher bias, we used rigorous awareness about PrEP, lack of funding and/or insurance, and procedures (described above) to select articles for the review. capacity and access. We also identified pharmaceutical- and The first two authors held seven weekly 60-min discussions population-specific barriers. Below we provide an account of to finalize the list of barriers and matching interventions and these barriers and the interventions that might address them, came to 100% agreement. This list was presented to the third thus improving PrEP implementation. Table 1 provides a (sociologist) and fourth (medical doctor) authors for further summary of these findings. 1 3 AIDS and Behavior Table 1 Summary of barriers to, and interventions to improve, PrEP implementation Conceptual Barriers to PrEP implementation Interventions matching specific barriers domain and inter- vention level Individual and Knowledge Knowledge Relationships Lack of training in PrEP provision Improved education of potential PrEP providers Domains: Disagreement/uncertainty about appropriate PrEP patients Development of trainings and interventions to assist providers in Provider Level Concerns/uncertainty about insurance coverage for PrEP identifying appropriate PrEP candidates Attitudes and beliefs Attitudes and beliefs Biases against patients’ race and sexual behaviors Development and delivery of trainings to increase provider “cul- Concerns about PrEP efficacy, toxicity, and resistance tural competency,” including trans- and gender-affirming care Concerns about patients’ disinhibition and risk compensation Interventions to identify and disrupt provider-held stereotypes leading to lack of adherence/compliance about potential PrEP users Individual and Knowledge Knowledge Relationships Low awareness of PrEP and low demand for PrEP Increased education and counseling to increase PrEP knowledge Domains: Attitudes and beliefs Attitudes and beliefs Patient Level Side effects; effectiveness; toxicities; interaction with femin- Development of supportive behavioral interventions (e.g., risk- izing hormones reduction, medication-adherence, and retention counseling) Managing multiple health concerns and PrEP side effects Assistance in navigating the healthcare system, including access- Prioritization of care for current conditions (e.g., pain or stress) ing health insurance and co-pay assistance above HIV prevention Referrals of patients with mental-health, substance-use, or “social” Prioritization of gender-affirming feminizing hormone therapy issues (e.g., housing insecurity) to social workers or community Distrust of medical system: structural racism, transphobia, and resources negative experiences Side-effect monitoring Competing priorities during periods of substance use Diminished concern for prevention with intimate partners Concerns about HIV-reporting systems, including potential insurance implications of a positive HIV result Unwillingness to discuss PrEP with primary care providers Community and Communication and awareness Communication and awareness Policy Lack of effective messaging about PrEP Community-engagement and community-mobilization strategies Domains: Lack of communication between healthcare providers and Systems to improve interagency/interprofessional collaboration Healthcare-Sys- community-based organizations Funding tem Level Funding General advocacy for expanded health insurance Limited health budgets to sustain PrEP programs Funding for medication costs, adherence counseling/monitoring, Lack of insurance coverage and financial-assistance programs and support services; referral to medication-assistance programs Capacity & access Capacity and access Lack of focus on “nonprescribing service providers” Expanded PrEP-delivery systems, staff, time, space, expertise Purview paradox: neither HIV specialists nor PCPs consider Engagement of generalist PCPs in PrEP provision for scale-up PrEP implementation within their clinical domain (addressing the purview paradox) Lack of training, referral systems, or established reimbursement Expanded/diversified settings providing PrEP (e.g., private prac- levels for care and drugs tices, mental-health clinics, ERs) and integration of PrEP into Legal constraints to providing PrEP for youth, including man- primary care dates to involve parental figures in working with minors Expanded education, screening, referrals to PrEP services Lack of access to care: inadequate transportation; inflexible Improved methods to identify appropriate PrEP candidates work schedules; inconvenient locations dispensing PrEP Specific guidelines from “normative bodies” (e.g., CDC, APA) Time constraints on medical appointments Partnerships between medical and social-service providers Lack of medical insurance and limited insurance networks Development of systems to monitor and evaluate PrEP use Lack of patient confidence and perseverance to access care Cross-training of staff (e.g., educators, pharmacists, nurses) Pharmaceutical barriers Improvements in pharmacists’ PrEP education Particular constraints of Truvada™ as PrEP (e.g., daily dosing Pharmaceutical barriers schedule, side effects) Advancing new PrEP technologies: innovative pharmacologic Population-specific barriers and stigma chemoprophylactic approaches (e.g., on-demand PrEP dosing, Lack of gender-affirming healthcare for transgender women injectable, microbicides, rings, films) Lack of trans-inclusive marketing of PrEP Pharmacokinetic studies of potential drug–drug interactions, par- Low prioritization of PrEP for people who inject drugs ticularly in oral PrEP medications and feminizing hormones Stigma associated with PrEP use and accessing HIV services Population-specific barriers and stigma The intersection of HIV-stigma with transphobia and homopho- Disaggregating transgender women from MSM in research and bia clinical practice and developing trans-inclusive research strate- gies Improving access to trans-competent PrEP providers Integrating PrEP care with contraceptive services Focusing resources on vulnerable communities Expanded “youth-friendly” health services, including augmented PrEP visit schedules, adherence clubs and social-support groups 1 3 AIDS and Behavior transportation) and medical burdens (e.g., side effects of Barriers to and Interventions with Potential to Improve PrEP Implementation PrEP) that complicate PrEP uptake. Perceived barriers, some not confirmed by strong evidence, included concerns about Individual and Relationships Domains—Provider Level effectiveness , toxicities [11, 14, 32, 69], and interac- tions with gender-affirming hormones among transgender Eighteen articles focused on primary care physicians, HIV women [56, 62]. Research cited the higher priority given to care for current conditions, both medical and psychosocial, and infectious-disease specialists, pharmacists, and nurse practitioners—including analyses of focus groups, inter- and gender-affirming hormone therapy than to HIP [46, 48, 49]. The “seasonal” nature of sexual risk trajectories was views, and surveys. None of the papers included data from social-service providers, though most of them mentioned also reported as a barrier to PrEP . Distrust of the medi- cal system based on historical legacies of structural racism, the need for the expansion of referrals to mental-health and other support services, care coordination, and peer-based transphobia, and other forms of discrimination was reported as a significant barrier to PrEP access [10, 62]. groups, all of which might improve PrEP implementation [10, 30, 32, 46, 57, 66]. Providers described concerns and The review also revealed a diminished concern about HIP when patients are in intimate partnerships and/or using solutions across socioecological levels. For instance, pro- posed system-level solutions included engaging generalist substances [46, 49], an unwillingness to discuss PrEP with primary care providers, and challenges managing mul- physicians in PrEP provision , community education campaigns , and increased funding for counseling and tiple health concerns, in addition to potential side effects from PrEP. While many of these barriers focused on the social support services . Significantly, many of these papers noted the “purview patient, we found that proposed interventions often neces- sitated system-level interventions (e.g., expanded access to paradox”—the idea that the providers who are best trained and most willing to prescribe PrEP (i.e., HIV specialists) and capacity for PrEP and targeted interventions to address population-specific barriers to PrEP). Individual-level solu- often do not see HIV-negative patients who would benefit from PrEP, while physicians who regularly care for HIV- tions proposed included targeting knowledge and awareness, attitudes, beliefs, and burdens; focusing on increased edu- negative patients (i.e., primary care physicians) are often not trained to provide PrEP [14, 56]. Other barriers included cation and counseling; and offering supportive behavioral interventions such as risk reduction, medication adherence, providers’ lack of knowledge, negative attitudes toward PrEP, lack of training in PrEP provision, disagreements and retention counseling [12, 17, 50, 56]. Interventions were proposed to help patients navigate healthcare systems and about who might be appropriate candidates for PrEP use, and concerns about insurance coverage for PrEP. The solu- improve the frequency of referrals to mental health, sub- stance abuse, and other supportive services. tions proposed to address knowledge gaps included trainings and interventions to assist providers in identifying appropri- Community and Policy Domains—Healthcare‑System Level ate PrEP candidates. We also found that prejudicial beliefs (e.g., assessments of the likelihood of risk behavior based Twenty studies consisted of broad reviews of existing PrEP on race) , concerns about the efficacy (or “real world” ec ffi acy) of PrEP, toxicities, and future resistance, and about literature or reviews of large-scale PrEP demonstration or implementation projects. These studies, as well as those patients’ behavior (e.g., sexual risk and lack of adherence) were often reported as substantial barriers to PrEP imple- focused on provider and potential-patient perspectives, addressed myriad system-level barriers to PrEP implemen- mentation . tation and proposed system-level solutions. We organized the system-level barriers into five categories: problems with Individual and Relationships Domains—Patient Level communication and awareness; lack of funding and/or insur- ance; lack of capacity and access; pharmaceutical barriers; Nine articles reported on primary data about potential and population-specific issues and stigma. PrEP patients’ attitudes, beliefs, and experiences. Most included qualitative interviews and results of focus groups Problems with Communication and Awareness Our review revealed a lack of effective messaging about PrEP and com- with community members. We considered data from pro- vider perspectives on patient-level barriers and solutions— munication between healthcare providers and community- based organizations . Proposed solutions in this domain for example, perceived barriers regarding increased risk behaviors associated with PrEP use. Barriers cited included included community engagement and mobilization strat- egies  as well as systems to improve interagency and patients’ lack of knowledge and low demand for PrEP, as well as socioeconomic (e.g., stigma and difficult access to interprofessional collaboration. 1 3 AIDS and Behavior Funding and/or Insurance Barriers Lack of funding is the social workers, educators, pharmacists, and nurses); leader- most consistently cited system-level barrier, including ship support of increased staff time to address financial bar - limited health budgets to sustain PrEP programs and lack riers ; and improving pharmacists’ PrEP education . of insurance coverage [9, 46, 47, 54, 56]. The latter has been framed as both a systems-level barrier to access and Pharmaceutical Barriers We identified barriers specific to care, with studies showing that patients without access Truvada™ and its oral daily dosing schedule and potential to insurance are less likely to successfully obtain PrEP side effects. Proposed solutions included advancing new ; and as a provider-level barrier, with insurance barri- PrEP technologies, such as pursuing innovative pharma- ers affecting providers’ attitudes and behaviors about pre- cologic chemoprophylactic approaches (e.g., on-demand scribing PrEP . The cost of PrEP is covered by many PrEP dosing, injectables, microbicides, rings, and films), health insurance plans . Gilead Advancing Access and pharmacokinetic studies of potential drug–drug inter- program, a commercial medication assistance program, actions, particularly involving those with feminizing hor- provides free PrEP to eligible HIV-negative adults in the mones [11, 62]. US with limited income and no insurance covering PrEP . However, individuals enrolled in government pro- Population‑Specific Issues and Stigma Several papers grams (e.g., Medicare Part D, Medicaid, TRICARE, or focused on transgender women [49, 53, 62], Black and VA) are not eligible for this program. Adolescents under Latina women , Black and Latino MSM , adoles- 18-years-old and young people covered by their parents’ cents [65, 66], men who engage in street-based sex work insurance, and who may wish to seek PrEP independently , heterosexual couples , and people who inject drugs to avoid disclosure through their parents’ Explanation of [43, 63]. These papers point to stigma associated with PrEP Benefits, are also excluded from this program [65, 66, 72]. use and the intersection of HIV-stigma with transphobia and Private insurers’ policies concerning medications, includ- homophobia [48, 49]. Despite the number of articles that ing PrEP, are insurance-specific and thus outside the identify stigma as a barrier to PrEP, few interventions were scope of this review. However, it is important to mention proposed that would directly address the effects of stigma. that insurers have enacted policies that may exacerbate existing barriers to PrEP implementation, such as prior Transgender Women Barriers specific to transgender authorization paperwork requirements, and strict require- women included non-inclusive marketing of PrEP; per- ments regarding completion of test results prior to author- ceived interactions with feminizing hormones and prioriti- izations and prescription renewals. In addition to suggest- zation of hormone care; managing multiple medical appoint- ing help for patients in navigating healthcare systems to ments and medications; mistrust arising from transphobia in access insurance and co-pay assistance programs, articles the medical system; and life instabilities and substance use. proposed general advocacy for expanded health insurance Proposed gender-affirming healthcare initiatives included , coverage of medication costs, PrEP adherence coun- prioritizing hormones and gender-affirming medical care, seling, and support services . exclusively using patients’ preferred names and pronouns, and creating safe spaces for trans clients . Studies also Capacity and Access Barriers included a lack of focus on proposed pharmacokinetic studies of potential drug–drug non-prescribing providers ; the purview paradox; lack interactions between oral PrEP medications and gender- of referral systems, and lack of training on, for example, affirming hormones in transgender women [11, 62]. Seve- when to initiate PrEP; legal constraints to providing PrEP lius et al.  argue that current deficits in the provision of for youth ; lack of access to care caused by inadequate gender-affirming care for transgender women are connected transportation, inflexible work schedules, time constraints to the conflation of transgender women with MSM, which during medical appointments , and inconvenience of serves to conceal transgender women’s unique social and locations dispensing PrEP; and lack of medical insurance. behavioral vulnerabilities. Solutions to these barriers included expanded space, time, and expertise for PrEP-delivery systems ; engagement Cisgender Black Women and Latinas Like transgender of generalist PCPs in PrEP provision (to address the purview women, cisgender Black women and Latinas face particu- paradox); diversification of settings providing PrEP (e.g., lar barriers to engaging with messages often designed for mental-health clinics and criminal-justice settings) ; MSM . PrEP implementation among women may be integration of PrEP into primary care; education, screen- helped by addressing the burden of frequent medical visits; ing, and referrals to PrEP; improved methods to identify the stigma associated with accessing HIV services; and the appropriate PrEP candidates ; stronger guidelines and burden of pill-taking, including concerns about adding to policies for providers ; partnerships between medical an existing pill burden. Increasing the availability of PrEP and social-service providers; cross-training of staffers (e.g., in settings where women receive services may also improve 1 3 AIDS and Behavior PrEP uptake, for example by integrating PrEP care with pro- Given the interconnected nature of the barriers identi- vision of contraceptives and screening for sexually transmit- fied, we recommend the adoption of a dynamic social- ted infections . systems model, as developed by Latkin and colleagues, for PrEP implementation in which individual, dyad, and Black and Latino Men Barriers for Black and Latino men structural factors are viewed as elements of a complex include decreased access to private health insurance and system in which none functions in isolation (p. S233) . more access through public clinics, as well as frequently We also suggest (below) specific targets of interventions endorsed stigma-related concerns about PrEP [47, 51]. based on Nunn et al.’s nine-step PrEP care continuum, Healthcare is a problematic area for MSM of color, who are analogous to the HIV Continuum of Care, as a model for more likely than other men to view talking about their sex PrEP implementation—identifying individuals at high lives to their doctors as a barrier to PrEP . Moreover, risk, increasing individual HIV-risk awareness, enhanc- research included in this review indicates that medical pro- ing PrEP awareness, facilitating PrEP access, linking to viders in training exhibit prejudicial assessments of Black PrEP care, prescribing PrEP, initiating PrEP, adhering to patients based on stereotypes about risk compensation (e.g., PrEP, and retaining individuals in PrEP care . Both increased condomless sex associated with PrEP use) . these models suggest multilevel interventions to achieve While this study was limited to current medical students, effective PrEP implementation. Multilevel interventions exploratory research surveying medical providers (primar- would integrate biomedical, behavioral, and structural or ily HIV specialists) suggests that providers’ likelihood to systemic components . Just as patients, providers, and prescribe PrEP varies widely across patient groups, making systems do not operate in isolation, proposed interventions the potential consequences of prejudicial assessments par- cannot be considered to perform isolated functions (e.g., ticularly troubling . These barriers underscore the limi- biomedical, behavioral, or structural). tations and potentially severe consequences of considering “PrEP navigation”—auxiliary, non-prescribing provid- seemingly individual-level interventions (such as provider ers whose role is to assist people in overcoming structural knowledge or individual behavior) in isolation from larger barriers to care  is an intervention whose potential systemic factors, such as structural racism. to address barriers in different socioecological domains has been acknowledged. The National Institutes of Health (NIH) has submitted requests for proposals for PrEP Discussion implementation programs, including a call for “PrEP navigator resource development and dissemination” . The purpose of this integrative review was to identify bar- A search of the NIH U.S. National Library of Medicine riers to PrEP implementation and interventions to improve reveals four clinical trials involving PrEP navigators  it. The 47 reviewed articles reported barriers at all four and the NIH Research Portfolio Online Reporting Tools domains of the conceptual framework. But these barriers (RePORT) reveals six projects on PrEP navigation for rarely exist in isolation, and proposed interventions are not Black MSM, young Latino MSM, women upon release always aligned to specific barriers. For instance, while a from incarceration, people who inject drugs (PWID), and number of papers (n = 18) focused exclusively on the per- methamphetamine users . Though promising, PrEP spectives, knowledge, and concerns of providers, these navigation is not likely to address many of the barriers papers rarely offered solutions to overcome barriers related identified by this review—for example; at the Individual to providers; instead, they offered solutions focused on tar - and Relationships Domains, primary care providers’ lack geting the behavior of individual patients, such as interven- of knowledge in identifying PrEP candidates and prescrib- tions to improve patient adherence  or evidence-based ing PrEP; and, at the systems level, lack of funding and interventions to reduce risk compensation . Moreover, insurance, and stigma. frequently cited barriers to PrEP implementation cut across Therefore, the combination of and future testing of the all three levels, as in the case of the purview paradox [14, effect of additional interventions is recommended. Clinic- 56], and also in the case of structural barriers, such as patient based interventions should include trainings to assist both distrust of the medical system based on historical legacies HIV-prevention and HIV-care providers in identifying of structural racism and of transphobia [10, 62]. Grounded appropriate PrEP candidates. Such training must target in our understanding of this literature, we provide a com- knowledge development (e.g., concerns about “real world” prehensive picture of how potential changes to PrEP imple- efficacy, toxicities, and future resistance); attitudes (e.g., mentation can be mapped onto specific barriers identified prejudicial beliefs and assessments of the likelihood of in the extant literature. In so doing, we are filling a research risk behavior based on race or gender identity); and social gap in the literature. norms about patients’ behavior (e.g., sexual risk and lack of adherence). Though provider training may improve PrEP 1 3 AIDS and Behavior Program Development and Quality Improvement Branch of the Na- implementation, system-level interventions (e.g., clinic tional Center for HIV/AIDS, Viral Hepatitis, STD and TB. funding and capacity) are needed to address population- specific barriers . Navigation suggests help for patients Human and Animal Rights No animals or humans were involved in in navigating healthcare systems to access insurance and this research. co-pay assistance programs; nonetheless, system-level advo- cacy is also needed for expanding health insurance, cover- Open Access This article is distributed under the terms of the Crea- age of medication, PrEP adherence counseling, and support tive Commons Attribution 4.0 International License (http://creat iveco mmons.or g/licenses/b y/4.0/), which permits unrestricted use, distribu- services. Furthermore, interventions that directly address the tion, and reproduction in any medium, provided you give appropriate effects of race- and gender-related stigma and racism may credit to the original author(s) and the source, provide a link to the improve participation of underserved groups (e.g., Black Creative Commons license, and indicate if changes were made. MSM and transgender women) in the HIV Continuum of Care and thus their access to PrEP. References Conclusion 1. Thompson MA, et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with Our approach and analysis highlight the structural dimen- HIV: evidence-based recommendations from an international sions of barriers to healthcare and public health and are association of physicians in AIDS care panel. Ann Intern Med. consistent with literature addressing tensions between indi- 2012;156(11):817–33. vidual- and system-level barriers , structural stigma 2. Cohen MS, McCauley M, Gamble TR. HIV treatment as preven- tion and HPTN 052. Curr Opin HIV AIDS. 2012;7(2):99. , and the shift from models of “cultural competency” to 3. Dodd PJ, Garnett GP, Hallett TB. Examining the promise of “structural competency” . One possible limitation of our HIV elimination by ‘test and treat’ in hyper-endemic settings. search terms is that we did not use the less common variation AIDS. 2010;24(5):729. “preexposure prophylaxis,” and some papers using such term 4. World Health Organization, Clinical Guidelines Across the Con- tinuum of Care: Linking people diagnosed with HIV infection to may have been missed. Nonetheless, based on our search, HIV care and treatment, in Consolidated guidelines on the use we identified, categorized, and analyzed barriers to PrEP of antiretroviral drugs for treating and preventing HIV infection: implementation and interventions at the patient, provider, Recommendations for a public health approach June 13. 2013, and healthcare-system levels. We argue for multilevel inter- World Health Organization: Geneva, Switzerland. p. 272. 5. CDC, High-impact HIV prevention: CDC’s approach to reduc- ventions that do not target providers, patients, or systems in ing HIV infections in the United States. 2011, Centers for Dis- isolation, but rather incorporate each of these levels into new ease Control & Prevention National Center for HIV/AIDS VH, models of implementation. We understand that our sugges- STD, and TD Prevention, Division of HIV/AIDS Prevention. tion that interventions target all three areas is challenging, 6. Grant RM, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. especially with regard to healthcare systems. As we know 2010;363(27):2587–99. from current political discourse, healthcare systems are dif- 7. Donnell D, et al. HIV protective efficacy and correlates of teno- ficult to change and must be viewed in the context of larger fovir blood concentrations in a clinical trial of PrEP for HIV political and structural realities that are challenging at best prevention. J Acquir Immune Defic Syndr. 2014;66(3):340. 8. Anderson PL, et al. Emtricitabine-tenofovir concentrations and and nearly impossible to navigate at worst. An awareness of pre-exposure prophylaxis efficacy in men who have sex with the challenges of healthcare systems, and the provision of men. Sci Transl Med. 2012;4(151):151. concrete solutions for those needing and seeking PrEP, can 9. Petroll AE, et al. PrEP awareness, familiarity, comfort, and pre- be valuable means of improving healthcare-system interven- scribing experience among US primary care providers and HIV specialists. AIDS Behav. 2017;21(5):1256–67. tions. Without attention to the ways structural factors affect 10. Wilton J, et al. Pre-exposure prophylaxis for sexually-acquired individuals within healthcare systems, PrEP implementation HIV risk management: a review. HIV/AIDS (Auckland, NZ). may actually reinforce existing inequities that place the over- 2015;7:125. whelming burden of the HIV epidemic on more-vulnerable 11. Mayer KH, et al. Antiretroviral pre-exposure prophylaxis imple- mentation in the United States: a work in progress. J Int AIDS groups. Soc. 2015;18(4 Suppl 3):19980. 12. Chan PA, et al. Retention in care outcomes for HIV pre-expo- Funding There is no funding attached to this manuscript. sure prophylaxis implementation programmes among men who have sex with men in three US cities. J Int AIDS Soc. Compliance with Ethical Standards 2016;19(1):20903. 13. Eaton LA, et al. Minimal awareness and stalled uptake of pre- exposure prophylaxis (PrEP) among at risk, HIV-negative, Conflict of interest Rogério M. Pinto declares that he has no conflict of black men who have sex with men. AIDS Patient Care STDs. interest. Kathryn Berringer declares that she has no conflict of interest. 2015;29(8):423–9. Rita Melendez declares that she has no conflict of interest. Okeoma Mmeje declares that she is a paid consultant (i.e., detailee) for the CDC 1 3 AIDS and Behavior 14. Krakower D, et al. HIV providers’ perceived barriers and facili- perspectives on PrEP-related risk compensation. AIDS Patient tators to implementing pre-exposure prophylaxis in care set- Care STDs. 2017;31(4):196–204. tings: a qualitative study. AIDS Behav. 2014;18(9):1712–21. 36. Blumenthal J, et al. Knowledge is power! Increased provider 15. Krakower DS, et al. Limited awareness and low immediate knowledge scores regarding pre-exposure prophylaxis (PrEP) are uptake of pre-exposure prophylaxis among men who have sex associated with higher rates of PrEP prescription and future intent with men using an internet social networking site. PLoS ONE. to prescribe PrEP. AIDS Behav. 2015;19(5):802–10. 2012;7(3):e33119. 37. Tellalian D, et al. Pre-exposure prophylaxis (PrEP) for HIV 16. Liu AY, et al. Limited knowledge and use of HIV post- and pre- infection: results of a survey of HIV healthcare providers evalu- exposure prophylaxis among gay and bisexual men. J Acquir ating their knowledge, attitudes, and prescribing practices. AIDS Immune Defic Syndr. 2008;47(2):241–7. Patient Care STDs. 2013;27(10):553–9. 17. Underhill K, et al. Implementation science of pre-exposure 38. Calabrese SK, et al. The impact of patient race on clinical deci- prophylaxis: preparing for public use. Curr HIV/AIDS Rep. sions related to prescribing HIV pre-exposure prophylaxis (PrEP): 2010;7(4):210–9. assumptions about sexual risk compensation and implications for 18. Hankins C, Macklin R, Warren M. Translating PrEP effective- access. AIDS Behav. 2014;18(2):226–40. ness into public health impact: key considerations for decision- 39. Castel AD, et al. Understanding HIV care provider attitudes makers on cost-effectiveness, price, regulatory issues, distribu- regarding intentions to prescribe PrEP. J Acquir Immune Defic tive justice and advocacy for access. J Int AIDS Soc. 2015;18(4 Syndr. 2015;70(5):520. Suppl 3):19973. 40. Spector AY, Remien RH, Tross S. PrEP in substance abuse treat- 19. Castel AD, Magnus M, Greenberg AE. Pre-exposure proph- ment: a qualitative study of treatment provider perspectives. Subst ylaxis for human immunodeficiency virus. Infect Dis Clin. Abuse Treat Prev Policy. 2015;10(1):1. 2014;28(4):563–83. 41. Hakre S, et al. Knowledge, attitudes, and beliefs about HIV pre- 20. Mugavero MJ, et al. The state of engagement in HIV care in the exposure prophylaxis among US Air Force Health Care Providers. United States: from cascade to continuum to control. Clin Infect Medicine. 2016;95(32):4511. Dis. 2013;57(8):1164–71. 42. Krakower DS, et al. Knowledge, beliefs and practices regard- 21. McLaren L, Hawe P. Ecological perspectives in health research. ing antiretroviral medications for HIV prevention: results from J Epidemiol Community Health. 2005;59(1):6–14. a survey of healthcare providers in New England. PLoS ONE. 22. Krieger N. A glossary for social epidemiology. J Epidemiol Com- 2015;10(7):e0132398. munity Health. 2001;55(10):693–700. 43. Edelman EJ, et al. Primary care physicians’ willingness to pre- 23. Krieger N. Theories for social epidemiology in the 21st century: scribe HIV pre-exposure prophylaxis for people who inject drugs. an ecosocial perspective. Int J Epidemiol. 2001;30(4):668–77. AIDS Behav. 2017;21(4):1025–33. 24. Whittemore R, Knafl K. The integrative review: updated method- 44. Smith DK, et al. PrEP awareness and attitudes in a national survey ology. J Adv Nurs. 2005;52(5):546–53. of primary care clinicians in the United States, 2009–2015. PLoS 25. Baeten JM, et al. Antiretroviral prophylaxis for HIV pre- ONE. 2016;11(6):e0156592. vention in heterosexual men and women. N Engl J Med. 45. Shaeer KM, et al. Exploratory survey of Florida pharmacists’ 2012;2012(367):399–410. experience, knowledge, and perception of HIV pre-exposure 26. Thigpen MC, et al. Antiretroviral preexposure prophylaxis for prophylaxis. J Am Pharm Assoc. 2014;54(6):610–7. heterosexual HIV transmission in Botswana. N Engl J Med. 46. Underhill K, et al. Access to healthcare, HIV/STI testing, and 2012;2012(367):423–34. preferred pre-exposure prophylaxis providers among men who 27. FDA, FDA approves first medication to reduce HIV risk. Silver have sex with men and men who engage in street-based sex work Spring; 2012. in the US. PLoS ONE. 2014;9(11):e112425. 28. Cypress BS. Rigor or reliability and validity in qualitative 47. Smith DK, et al. Attitudes and program preferences of African- research: perspectives, strategies, reconceptualization, and rec- American urban young adults about pre-exposure prophylaxis ommendations. Dimens Crit Care Nurs. 2017;36(4):253–63. (PrEP). AIDS Educ Prev. 2012;24(5):408–21. 29. Strauss A, Corbin JM. Basics of qualitative research: Grounded 48. Collier KL, Colarossi LG, Sanders K. Raising awareness of theory procedures and techniques. Thousand Oaks: Sage Publica- pre-exposure prophylaxis (PrEP) among women in New York tions; 1990. City: community and provider perspectives. J Health Commun. 30. Calabrese SK, et al. Putting PrEP into practice: lessons learned 2017;22(3):183–9. from early-adopting US providers’ firsthand experiences providing 49. Sevelius JM, et al. ‘I am not a man’: trans-specific barriers and HIV pre-exposure prophylaxis and associated care. PLoS ONE. facilitators to PrEP acceptability among transgender women. 2016;11(6):e0157324. Global Public Health. 2016;11(7–8):1060–75. 31. Krakower DS, et al. Primary care clinicians’ experiences prescrib- 50. Taylor SW, et al. Optimizing content for pre-exposure prophy- ing HIV pre-exposure prophylaxis at a specialized community laxis (PrEP) counseling for men who have sex with men: perspec- health centre in Boston: lessons from early adopters. J Int AIDS tives of PrEP users and high-risk PrEP naive men. AIDS Behav. Soc. 2016. https ://doi.org/10.7448/IAS.19.1.21165 . 2014;18(5):871–9. 32. Arnold EA, et al. A qualitative study of provider thoughts on 51. Lelutiu-Weinberger C, Golub SA. Enhancing PrEP Access implementing pre-exposure prophylaxis (PrEP) in clinical settings for Black and Latino Men Who Have Sex With Men. J Acquir to prevent HIV infection. PLoS ONE. 2012;7(7):e40603. Immune Defic Syndr. 2016;73(5):547–55. 33. Blackstock OJ, et al. A cross-sectional online survey of HIV pre- 52. Raifman JR, Flynn C, German D. Healthcare provider contact and exposure prophylaxis adoption among primary care physicians. J pre-exposure prophylaxis in Baltimore men who have sex with Gen Intern Med. 2017;32(1):62–70. men. Am J Prev Med. 2017;52(1):55–63. 34. Puro V, et al. Attitude towards antiretroviral pre-exposure prophy- 53. Galindo GR, et al. Community member perspectives from laxis (PrEP) prescription among HIV specialists. BMC Infect Dis. transgender women and men who have sex with men on pre-expo- 2013;13(1):217. sure prophylaxis as an HIV prevention strategy: implications for 35. Calabrese SK, et al. “Support Your Client at the Space That implementation. Implement Sci. 2012;7(1):116. They’re in”: HIV pre-exposure prophylaxis (PrEP) prescribers’ 1 3 AIDS and Behavior 54. Doblecki-Lewis S, et al. Healthcare access and PrEP continuation 68. Hojilla JC, et al. Sexual behavior, risk compensation, and HIV pre- in San Francisco and Miami after the US PrEP demo project. J vention strategies among participants in the San Francisco PrEP Acquir Immune Defic Syndr. 2017;74(5):531–8. demonstration project: a qualitative analysis of counseling notes. 55. Golub SA, Operario D, Gorbach PM. Pre-exposure prophylaxis AIDS Behav. 2016;20(7):1461–9. state of the science: empirical analogies for research and imple- 69. McMahon JM, et al. Oral pre-exposure prophylaxis (PrEP) for mentation. Curr HIV/AIDS Rep. 2010;7(4):201–9. prevention of HIV in serodiscordant heterosexual couples in the 56. Silapaswan A, Krakower D, Mayer KH. Pre-exposure prophy- United States: opportunities and challenges. AIDS Patient Care laxis: a narrative review of provider behavior and interventions to STDs. 2014;28(9):462–74. increase PrEP implementation in primary care. J Gen Intern Med. 70. Centers for Disease Control and Prevention. PrEP. 2018; https :// 2017;32(2):192–8.www.cdc.gov/hiv/basic s/prep.html. 57. Burns DN, et al. Role of oral pre-exposure prophylaxis (PrEP) 71. Gilead Sciences Inc. Gilead Advancing Access. 2018; https :// in current and future HIV prevention strategies. Curr HIV/AIDS www.gilea dadva ncing acces s.com/. Rep. 2014;11(4):393–403. 72. Doll M, et al. Linking HIV-negative youth to prevention services 58. Doblecki-Lewis S, Cohen S, Liu A. Clinical treatment options in 12 US cities: barriers and facilitators to implementing the HIV infectious diseases: update on PrEP implementation, adher- prevention continuum. J Adolesc Health. 2017;62:424–33. ence, and advances in delivery. Curr Treat Options Infect Dis. 73. Adams LM, Balderson BH. HIV providers’ likelihood to prescribe 2015;7(2):101–12. pre-exposure prophylaxis (PrEP) for HIV prevention differs by 59. Krakower DS, Mayer KH. Pre-exposure prophylaxis to prevent patient type: a short report. AIDS Care. 2016;28(9):1154–8. HIV infection: current status, future opportunities and challenges. 74. Latkin C, et al. A dynamic social systems model for considering Drugs. 2015;75(3):243–51. structural factors in HIV prevention and detection. AIDS Behav. 60. Rowniak S. PrEP: a case study. J Am Assoc Nurse Pract. 2010;14(2):222–38. 2015;27(6):296–9. 75. Nunn AS, et al. Defining the HIV pre-exposure prophylaxis care 61. Krakower D, Mayer KH. Engaging healthcare providers to imple- continuum. AIDS (London, England). 2017;31(5):731. ment HIV pre-exposure prophylaxis. Curr Opin HIV AIDS. 76. NIH. NLM Requests Quotations for 2017 HIV/AIDS Community 2012;7(6):593. Information Outreach Projects. 2017 June 01, 2017 March 27, 62. Sevelius JM, Deutsch MB, Grant R. The future of PrEP among 2018; h tt ps : // w ww . nl m. n ih .g ov / news/ n lm _r f q_ h iv _a i ds _ ou tr e transgender women: the critical role of gender affirmation in ach_2017.html. research and clinical practices. J Int AIDS Soc. 2016. https ://doi. 77. Medicine U.S.N.L.o. ClinicalTrials.gov Database. https ://clini caltr org/10.7448/IAS.19.7.21105. ials.gov/. 63. Marshall BD, Milloy MJ. Improving the effectiveness and delivery 78. US Department of Health and Human Services, Research Portfolio of pre-exposure prophylaxis (PrEP) to people who inject drugs. Online Reporting Tools (RePORT). Addiction. 2017;112(4):580–2. 79. Pinto RM, et al. Factors that inu fl ence linkages to HIV continuum 64. Mansergh G, Koblin BA, Sullivan PS. Challenges for HIV pre- of care services: implications for multi-level interventions. Int J exposure prophylaxis among men who have sex with men in the Environ Res Public Health. 2017;14(11):1355. United States. PLoS Med. 2012;9(8):e1001286. 80. Metzl JM. Structural competency. Am Q. 2012;64(2):213–8. 65. Burda JP. PrEP and our youth: implications in law and policy. 81. Hatzenbuehler ML, Link BG. Introduction to the special issue on Columbia J Gender Law. 2015;30:295. structural stigma and health. Social Sci Med. 2014;103:1–6. 66. Hosek S, et al. Preventing HIV among adolescents with oral PrEP: 82. Metzl JM, Hansen H. Structural competency: theorizing a new observations and challenges in the United States and South Africa. medical engagement with stigma and inequality. Soc Sci Med. J Int AIDS Soc. 2016. https ://doi.org/10.7448/IAS.19.7.21107 . 2014;103:126–33. 67. Liu A, et al. Early experiences implementing pre-exposure proph- ylaxis (PrEP) for HIV prevention in San Francisco. PLoS Med. 2014;11(3):e1001613. 1 3
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