Assessing Structural Racism and Discrimination Along the Pre-exposure Prophylaxis Continuum: A Systematic Review

Structural racism and discrimination (SRD) is deeply embedded across U.S. healthcare institutions, but its impact on health outcomes is challenging to assess. The purpose of this systematic literature review is to understand the impact of SRD on pre-exposure prophylaxis (PrEP) care continuum outcomes across U.S. populations who could benefit from HIV prevention. Guided by PRISMA guidelines, we conducted a systematic review of the published literature up to September 2023 using PubMed and PsycInfo and included peer-reviewed articles meeting inclusion criteria. At least two authors independently screened studies, performed quality assessments, and abstracted data relevant to the topic. Exposure variables included race/ethnicity and any level of SRD (interpersonal, intra- and extra-organizational SRD). Outcomes consisted of any steps of the PrEP care continuum. A total of 66 studies met inclusion criteria and demonstrated the negative impact of SRD on the PrEP care continuum. At the interpersonal level, medical mistrust (i.e., lack of trust in medical organizations and professionals rooted from current or historical practices of discrimination) was negatively associated with almost all the steps across the PrEP care continuum: individuals with medical mistrust were less likely to have PrEP knowledge, adhere to PrEP care, and be retained in care. At the intra-organizational level, PrEP prescription was lower for Black patients due to healthcare provider perception of higher sex-risk behaviors. At the extra-organizational level, factors such as homelessness, low socioeconomic status, and incarceration were associated with decreased PrEP uptake. On the other hand, healthcare provider trust, higher patient education, and access to health insurance were associated with increased PrEP use and retention in care. In addition, analyses using race/ethnicity as an exposure did not consistently show associations with PrEP continuum outcomes. We found that SRD has a negative impact at all steps of the PrEP care continuum. Our results suggest that when assessing the effects of race/ethnicity without the context of SRD, certain relationships and associations are missed. Addressing multi-level barriers related to SRD are needed to reduce HIV transmission and promote health equity. Supplementary Information The online version contains supplementary material available at 10.1007/s10461-024-04387-y.


Introduction
Structural racism is deeply embedded in the structures and institutions of U.S. society.Structural racism and discrimination (SRD) refers to the conditions that limit opportunities, resources, power, and well-being of individuals and populations based on race and ethnicity and other statuses leading to poorer health outcomes [1].Health disparities have been demonstrated across many racial and ethnic groups, notably Black, Latinx, American Indian, and Alaska Native people, who experience higher rates of cardiovascular disease, diabetes, asthma, hypertension, and obesity than their White counterparts, in large part due to structures and systems of resource allocation (e.g.poor access to healthcare, education, and healthy food) stemming from SRD [2].In addition to these chronic health conditions, HIV incidence is disproportionately high among Black and Latinx individuals, especially men who have sex with men (MSM), even almost 30 years after the pandemic's peak [3].This disparity in HIV incidence is further complicated by the potential for intersectional discrimination based on gender and sexuality.
Approved by the Food and Drug Administration (FDA) in 2012, oral Pre-exposure Prophylaxis (PrEP), when taken as prescribed, provides greater than 90 percent protection against acquiring HIV [4].The newer developments of injectable PrEP, given every two months as opposed to a daily regimen [5,6], and the PrEP "On-Demand" dosing regimen, taken 2-24 h before and 24-48 h after a potential HIV exposure [7] have expanded the accessibility of PrEP.Despite its high efficacy, multiple methods of administration, and a variety of dosing schedules, PrEP use is lowest among Black and Latinx people, although these groups have the highest HIV incidence rates.In 2022, only 8% of Black people eligible for PrEP were prescribed it, compared to 14% of Latinx people, and 60% of White people [8].The steps of the PrEP continuum include increasing PrEP awareness, PrEP prescription, initiation and use of PrEP, PrEP adherence, and retention in care [9].Each step can become a barrier to access for marginalized groups, leading to the low rates of PrEP usage in comparison to White individuals.
One limitation of current approaches to reducing disparities in PrEP usage is that most studies treat race/ethnicity as a risk factor for poor health outcomes but do not consider lived experiences with SRD.Using SRD along with race/ethnicity as an exposure leads to a more accurate conversation surrounding the impact of structural factors on disparities in the PrEP care continuum.Despite the variety of successful interventions that aim to reduce this well-documented disparity in PrEP usage, the persistence of the disparity asks us to reexamine our understanding and frameworks of how and why it continues to exist.
We aim to review the current literature concerning the impact of SRD on access to PrEP care for Black and Latinx people, with the goal of addressing existing gaps and retaining patients in the PrEP care continuum.The goal of this systematic review of the published literature is to assess peer-reviewed studies that have used SRD and/or race/ ethnicity as the exposure in PrEP-related health outcomes to better understand the enduring disparities in the PrEP continuum and inform interventions that can be tailored to address these disparities.

Methods
We followed the guidelines set forth by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for systematic reviews.Additionally, we registered this systematic review with PROSPERO (registration number: CRD42022350803), an international database of prospective systematic reviews.After a preliminary review of the published literature, we consolidated a list of relevant keywords and used these to create our unique search string based on the PICO (patient, population, or problem; intervention; comparison; outcome) framework for systematic reviews.

Defining Exposures and Outcomes
Our exposures included self-reported race/ethnicity and multi-level exposures to SRD.SRD operates across distinct yet interconnected levels, and we have chosen to examine the interpersonal (first level), intra-organizational (second level), and extra-organizational (third level) [10].The interpersonal level involves personal beliefs or stereotypes that influence interactions between individuals, such as the use of insensitive language or differential treatment recommendations.The intra-organizational level encompasses discriminatory practices within institutions, including clinic policies and organizational procedures that perpetuate racial inequities.SRD at the extra-organizational level deals with the cumulative effects of historical, cultural, and policy-driven mechanisms that perpetuate racial disparities through factors like access to education, economic opportunities, immigration policies, housing instability, and neighborhood conditions.
Regarding outcomes, our study assessed quantifiable effects on each stage of the PrEP care continuum (Fig. 1).The PrEP care continuum encompasses the full spectrum of care and support provided to individuals who are using PrEP and includes: PrEP awareness, uptake, adherence, and retention.We also included studies that evaluated HIV testing, such as previous testing and future intentions to get tested.As a negative test is needed to confirm serostatus before beginning PrEP, this outcome is pertinent to the PrEP care continuum.Lastly, the PrEP-to-Need Ratio, which assesses the adequacy of PrEP utilization, was included as an outcome relevant to the PrEP care continuum [11].

Search Strategy
A comprehensive search strategy was devised to identify relevant studies.The search was conducted using electronic databases, including PubMed and PsycINFO, to ensure coverage of medical, psychological, and social science literature.The search strategy was updated in September 2023 to include the latest research findings and ensure the most up-to-date information.The key search terms and keywords included but were not limited to: "HIV Pre-exposure Prophylaxis", "Racism", "Discrimination", "Health Disparities".The search strategy was developed using a combination of Medical Subject Headings (MeSH) terms, Boolean operators, and free-text terms to capture all relevant articles (full search strategy found in supplemental materials).The search was restricted to articles published in English.

Study Selection
The initial search yielded a comprehensive list of articles related to the impact of SRD on the PrEP care continuum.Two reviewers independently screened the titles and abstracts to identify relevant articles.For abstracts where there was not a consensus on relevance, a third reviewer was invoked to review the full-text article and resolve the conflict.Our team then evaluated the full-text articles of the selected abstracts to assess their eligibility for inclusion in the systematic review.We used the following selection criteria: 1. Studies that examined the impact of SRD on any of the steps of the PrEP care continuum.
2. We included quantitative and mixed-method studies that measured the impact of SRD across the PrEP care continuum.We excluded purely qualitative studies to focus on quantitative methods which are able to capture population-level data.3. Studies that were based in the U.S. and published in peer-reviewed journals from January 2012 through September 2023, as the use of fixed dose combination of emtricitabine/tenofovir disoproxil fumarate as PrEP was approved by the U.S. Food and Drug Administration in 2012.

Data Extraction and Synthesis
Two reviewers extracted relevant data independently using a standardized data extraction form.The following information was captured from each included study and entered into a table in Microsoft Excel: study characteristics (author, year of publication, study design), participant characteristics (sample size, demographic information), measures or instruments used to assess SRD, PrEP care continuum outcomes, and findings related to the impact of SRD on PrEP outcomes.

Quality Assessment
Four reviewers independently evaluated the risk of bias and the overall quality of each study using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies [12] and the Newcastle-Ottawa Scale (NOS) for nonrandomized studies such as case control and cohort studies [13].Using both scales, we assessed quality of the study question, sampling method, measurement of exposures, control for confounding variables, and adequacy of follow-up if applicable.Any discrepancies in quality assessment were resolved through discussion and consensus.

Data Analysis
We summarized and presented the results thematically across the steps of the PrEP care continuum.

Results
Out of 904 studies, 66 met the inclusion criteria and were included in the review (Fig. 2).The initial PubMed search retrieved 479 articles, and PsycInfo retrieved 425 articles.Upon reviewing abstracts and after duplicates were removed, we included 181 articles to review for further assessment of inclusion criteria.Upon reviewing the full texts, an additional 115 articles were excluded, and the remaining 66 peerreviewed studies were included in our analysis.

Types of Participants and Settings
Table 1 provides a comprehensive overview of included studies.The composition of participants in the included studies varied, with the majority consisting of PrEP users and/or individuals eligible for PrEP.Additionally, a handful of studies evaluated healthcare providers [14,15] and medical or pharmacy students [16][17][18][19][20] as primary subjects.Participant demographics encompassed diverse intersections of racial/ethnic groups, gender identities, and sexual orientations, most prominently Latinx, Black, MSM, sexual minority men (SMM), transgender women (TW).White participants were frequently employed as the primary comparator group for statistical analysis, allowing for comparisons and assessments of racial/ethnic disparities in PrEP care.

Measurements of SRD
Studies exhibited significant heterogeneity in their measurement of SRD.A total of 17 studies used validated measures to assess SRD exposures.The Modern Racism scale was used in three studies, which is a measure of covert racial prejudice and attitudes [14,16,36].The Group-Based Medical Mistrust Scale measures health care-related trust with a specific focus on the context of racism and discrimination [37][38][39].Two studies utilized the HIV/AIDS conspiracy belief scale [40,41], while another study created two scales adapted from the original scale to measure "genocidal" and "treatment-related" conspiracy beliefs [42].Four studies used the Racial Implicit Association Test [14,[17][18][19], while another study used three subscales from the Color-Blind Racial Attitudes Scale [43].Ten studies created and validated new scales or adapted questions from previous studies to create new unvalidated tools.Most studies captured sociodemographic information about participants, and some studies relied solely on self-reported race as the exposure of interest, without further measurement of specific forms of SRD.PrEP outcome measures, recorded in Table 1, were heterogeneous but not completely mutually exclusive across studies and are listed in detail below.

PrEP Knowledge and Awareness
Heightened medical mistrust was associated with reduced comfort in discussing PrEP with healthcare providers and a lower odds of PrEP awareness [38,39].Likewise, perceived healthcare-related discrimination was negatively linked to PrEP awareness and to a reduced likelihood of talking to providers about having sex with men [44].The inverse was true as well: increased provider trust was associated with increased PrEP awareness and use among Black patients.For Latino MSM specifically, lower educational attainment and lower levels of reported household income were associated with decreased PrEP awareness [45].For Black and Latino men and Black TW, incorrect beliefs about PrEP, concerns about side effects, and belief in conspiracy theories negatively correlated with PrEP awareness and knowledge [40,42,[46][47][48].Some studies found that race/ethnicity, residential instability, and incarceration were not associated with  decreased PrEP awareness but that increased awareness was positively associated with higher education, access to insurance, identifying as Black, and prior HIV testing [46,[49][50][51].Similarly, for young Black MSM compared to young White MSM, food insecurity was associated with increased levels of stress, which was associated with reduced PrEP awareness [52].In summary, SRD at the interpersonal level (medical mistrust, perceived discrimination) and extraorganizational level (low education, low health literacy, low income, poor access to insurance and food) were negatively associated with PrEP knowledge and awareness [53].

HIV Testing
The association between SRD exposures at the three levels and HIV testing were mixed: some studies showed that belief in HIV conspiracies and perceived racial discrimination were associated with higher HIV testing [41,54], while other studies showed that patient experiences of racism and homophobia, perceived systematic discrimination in access to or policies regarding HIV-related services were associated with decreased HIV testing.[21,25] At the extraorganizational level, some studies showed that homelessness or anxiety associated with food insecurity and housing instability were associated with higher HIV testing [52,55] while other studies showed that primary language other than English, lower education, lower income, lack of a regular healthcare provider, and lack of insurance were associated with decreased HIV testing [56,57].For Latinx immigrants, misunderstanding about immigration laws and policies, being undocumented, recent immigration, having a low perception of risk, and not being offered an HIV test post-immigration were associated with decreased or no HIV testing [56,[58][59][60].

PrEP Prescription and Initiation
People self-identifying as White or Asian had higher rates of PrEP prescription [61][62][63], while those self-identifying as African American or Latinx or having lower income had lower rates of PrEP prescription [27,29,30].Willingness to use PrEP was positively associated with a variety of sociodemographic factors and SRD exposures, including higher age, higher educational level, trust in primary care provider, PrEP awareness, perceived likelihood of acquiring HIV, and living in an area with higher PrEP clinic density [33,50,64].Decreased willingness to initiate PrEP was associated with extra-organizational SRD, such as low socioeconomic status, living in neighborhood with greater proportion of residents below poverty line, low education, residing within city limits, housing instability, and history of incarceration [33,37,52,65,66].At the interpersonal and extra-organizational level, experiences of discrimination Latino sexual minority men discrimination and higher levels of anticipated discrimination were associated with less PrEP use [24,72,77].Notably, experienced racism was associated with greater comfort in receiving PrEP through mail-home-delivery [78].Barriers to use were anticipated racial stigma, having to take a pill every day, having to talk to their doctor about their sex life, medical mistrust, cost concerns, insurance issues, and lack of knowledge [38,39,47,48,67,74].Latinx immigrants faced further barriers, including experienced discrimination related to immigration status and privacy concerns [56,72,74].

PrEP Adherence and Retention
PrEP adherence decreased as levels of medical mistrust experienced by patients increased [38,73].Additionally, PrEP adherence varied between different neighborhoods with neighborhoods predominantly composed of Black and Latinx communities exhibiting lower rates of adherence [26].Moreover, two studies demonstrated that higher rates of PrEP discontinuation were associated with lower socioeconomic status and utilization of public health insurance [26,27].Surprisingly, one study found that higher levels of daily discrimination were associated with an increased likelihood of future PrEP use as well as higher levels of resilience and social support [77].Similar to the outcome of PrEP knowledge and awareness, this stage of the continuum was associated with SRD at the first level (medical mistrust, discrimination) and third level (neighborhood composition, socioeconomic status, public health insurance usage).

Discussion
These studies provide valuable insights into the complex dynamics and systemic factors influencing access, utilization, and outcomes within the PrEP care continuum.The diverse array of study designs utilized contributed to a comprehensive understanding of the impact of SRD on the PrEP care continuum, encompassing both individual experiences and broader structural factors.The use of validated measures provided a robust foundation for examining the impact of SRD on PrEP outcomes and allowed for more nuanced analyses.On the other hand, self-reported surveys provided direct insight into participants' experiences.In some studies, self-reported race/ethnicity was not associated with PrEP care continuum outcomes but instead was associated with SRD at multiple levels (i.e., provider trust, history of incarceration, limited access to healthcare, lack of health insurance, the stigma associated with disclosing sexual orientation to a healthcare provider).The mixed results regarding the association between race/ethnicity and PrEP care continuum outcomes demonstrate the importance by police and law enforcement, anticipated racial stigma, and identities at the intersection of racial-sexual minority status were associated with decreased willingness to initiate PrEP [66,67].Negative exposures specific to the healthcare setting included higher race-based medical mistrust scores, medical mistrust in general, discomfort talking about sexual health with a provider, and having conspiracy beliefs [37,38,42,68].Intra-organizational SRD was demonstrated by the fact that healthcare providers and medical students who scored high on modern racism measures were less inclined to prescribe PrEP to Black patients [15,16].Black patients were sometimes assumed to be non-adherent [17,19] and other times judged as more responsible [14,18], which had negative and positive effects on the intention to prescribe, respectively.Medical students were less willing to prescribe PrEP to Black MSM compared to White MSM due to concerns about sexual risk compensation, where a decrease in the perceived risk of getting HIV (due to taking PrEP) may lead to increased HIV risk behaviors [20].

PrEP Use
Facilitators for PrEP use included greater levels of education, full-time employment, greater annual household income, and having health insurance [23,35,45,49,[69][70][71][72].Black patients who heard about PrEP from a variety of external sources (e.g.family, friends, healthcare providers, media) were more likely to use PrEP [51].On the other hand, White patients who discussed PrEP with a provider were more likely to use PrEP than Black patients who discussed PrEP with a provider [73].For Latino SMM specifically, facilitators were PrEP knowledge, PrEP affordability, previous HIV testing, healthcare navigation support, and positive provider demeanor [39,47,60,71,74], encompassing exposures at all three levels of SRD.
Regarding decreased PrEP use, extra-organizational level SRD, such as housing instability, homelessness, history of incarceration, limited access to healthcare, and lack of insurance, were associated with decreased PrEP uptake [23,46,52,53,69,72].Individuals experiencing unstable housing conditions were less likely to utilize PrEP effectively [30,75].Low socioeconomic status was associated with lower rates of PrEP use even after being prescribed [28,29,45].When examining race/ethnicity, Black and Latino MSM, compared to White MSM, had lower levels of PrEP use, and PrEP use among Black adolescents differed geographically, with 6% of Black adolescents using PrEP in New Orleans and 11% in Los Angeles [28,76].Lower access to PrEP clinics was associated with decreased PrEP use in under-resourced neighborhoods, which were communities with predominantly Black and Latinx residents as well as populations below the federal poverty line [35].At the interpersonal level, income and immigration status of understanding how contextual factors, rather than race/ ethnicity itself, affect PrEP health services utilization and outcomes.
We found that medical mistrust was the factor most associated with a lack of PrEP knowledge and awareness.Medical mistrust was often measured alongside and correlated with measures of perceived discrimination and belief in conspiracy theories; the suggested relationship between these three exposures raises the need to understand how these constructs (in isolated and aggregate form) affect the patients' experiences with the healthcare system.Additionally, discussing PrEP with a healthcare provider seem to differ for patients within the same race due to factors including age, geography, and gender identity [28,51,68,73].Although standards for clinical research and patient protection have significantly improved in past decades, more work needs to be done to address the negative impact of medical mistrust on patient care.Our findings emphasize the need to address medical mistrust as a form of SRD that hinders several steps along the PrEP care continuum, especially PrEP knowledge and awareness.
Of the papers that examined PrEP prescription and initiation, the prominent SRD exposure was racial bias in both medical trainees and PrEP providers.At this point in the continuum, patients have had contact with the healthcare system and have received HIV testing and their providers are aware that they may benefit from PrEP.Studies show that the concept of "risk compensation" was often the reason that providers would not prescribe PrEP to their patients.This reasoning was mostly applied to racial/ethnic minority patients and usually not to their White counterparts and persists despite ample evidence that PrEP use does not result in behavior change or an increase in sexually transmitted infections [79].This bias is a form of SRD that is deeply rooted in the medical system, as evidenced by its presence at different levels of medical training.The incorrect assumptions about risk perception and behavior in racial minorities hinder PrEP prescription and initiation.Further, the lack of proactive prescribing and engagement with racial/ethnic minority populations leads to limited opportunities for PrEP discussions and education, further hindering awareness levels.Together, these findings suggest an imperative need for more informed medical decision-making to improve PrEP prescription and initiation.Putting it all together, negative perceptions of Black patients influencing clinical decisions exemplify SRD at the interpersonal level.Racial differences in the likelihood of discussing PrEP with a healthcare provider can be classified as both first-level SRD as well as second-level SRD, as this may be due to a lack of organizational procedures and protocols in place to ensure that patients in need are not deprived of PrEP.
Social determinants of health have a notable association with PrEP uptake and use.The association between lower socioeconomic status (SES) and lower PrEP uptake can be attributed to the fact that Black and Latinx individuals are more likely to belong to lower SES groups.Similarly, Black and Latinx communities have been and continue to be disproportionately affected by housing instability due to the historical legacy of slavery and racial discrimination, including housing discrimination, in the U.S. Another important social determinant is the inequitable distribution of PrEPprovider clinics, which disproportionately affects Black and Latinx communities.Because PrEP has shown efficacy in decreasing HIV incidence in regions with the greatest PrEP uptake [80], this discrepancy suggests the need for further examination of the complex interplay between clinic accessibility as SRD and PrEP uptake in under-resourced communities.Addressing these forms of SRD is crucial for promoting equitable PrEP access and utilization, reducing health disparities, and achieving health equity for all populations.
We found that PrEP adherence and retention were negatively impacted by medical mistrust and social determinants of health, both of which also influenced earlier stages of the PrEP care continuum.The fact that medical mistrust has an impact this far down the continuum demonstrates that medical mistrust works at different levels of the healthcare system and highlights the importance of building trust and effective patient-provider relationships.Additionally, the presence of socio-economic disparities and unequal access to healthcare resources contribute to challenges faced by marginalized communities, ultimately affecting their ability to adhere to PrEP regimens effectively.This highlights the significant role that neighborhood factors and SES play in PrEP adherence and retention.These findings emphasize the need for targeted interventions addressing both interpersonal and extra-organizational racism to enhance PrEP adherence and ensure equitable access and utilization of this preventive measure.
One population highlighted by our study was that of Latinx immigrants, who had unique barriers to PrEP use, including experienced discrimination regarding immigration status and privacy concerns [56,72,74].Since Spanish language PrEP navigation services are often less geographically accessible for Latin American-born Latino sexual minority men compared to their US-born counterparts [34], it is important to point out the finding that navigation support is a facilitator to PrEP use [74].Combining PrEP education with existing educational efforts focused on healthcare access and legal protections as an immigrant may be even more useful, as misunderstandings about immigration laws and policies were associated with participants having never undergone HIV testing [58,81].

Fig. 1
Fig. 1 PrEP Care Continuum in the context of SRD

Fig. 2
Fig. 2 PRISMA flow diagram: systematic review of SRD and the PrEP care continuum

Table 1
Causes of oesophageal perforation

Table 1 (
Men who have sex with men; BLMSM: Black and Latino men who have sex with men; BMTW: Black men and transgender women who have sex with men; WMTW: White men and transgender women who have sex with men; SMM: sexual minority men; GBMMS: Group Based Medical Mistrust Scale; SMMTW: Sexual minority men and transgender women; LSMM: