Barriers to the Wider Use of Pre-exposure Prophylaxis in the United States: A Narrative Review

We assessed peer-reviewed papers and conference abstracts to identify barriers to PrEP uptake in the USA among those at risk for HIV by searching PubMed, International AIDS Conference 2019, and Conference on Retroviruses and Opportunistic Infections 2019 abstracts, using the terms “PrEP OR pre-exposure prophylaxis OR pre-exposure prophylaxis” AND “HIV” AND “clinical trial OR classical article OR clinical study OR comparative study OR meta-analysis OR multicenter study OR observational study OR qualitative research OR barriers”. As this field is rapidly evolving, we focused on articles from 2016 onwards. Key themes were identified from the initial search: knowledge/awareness of PrEP; perception of HIV risk; social stigma; provider bias and distrust of healthcare providers/systems; lack of access to medical care; lack of access to (or awareness of) financial assistance options; and PrEP side effects and medication interaction concerns (Table 1). Each of the identified barrier categories was reviewed with consideration of individual behavioral and sociodemographic factors, as well as healthcare provider/systemic factors. Other relevant references were identified for each category either from the bibliography of original articles or by carrying out additional PubMed searches during manuscript development on “PrEP OR preexposure prophylaxis OR pre-exposure prophylaxis” AND “HIV” AND (knowledge OR awareness OR risk perception OR stigma OR bias OR distrust OR access OR cost OR side effects OR interaction). This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

Before any other factors influencing PrEP uptake come into play, both individuals at risk and healthcare providers need to be aware of the existence of PrEP as a preventive option. Nationally, in the general population, awareness of PrEP is low. In a survey of 19,806 adults in the USA (general public) between 2009 and 2014, only 6.5% reported awareness of PrEP [17]. More recent national data are not available, but smaller studies suggest that general awareness remains low. A 2018 study of the North Carolina general public (N = 409) found that only 9% had heard of PrEP [18]; a 2018 Southern Arizona study (N = 500) noted that only 20% of individuals surveyed at public health department clinics (which provided family planning and sexually transmitted infection testing/treatment) were aware of PrEP [19].

In populations at high risk for HIV acquisition, PrEP awareness varies and study findings are often contradictory. For example, relatively high knowledge/awareness of PrEP among racially and ethnically diverse populations of MSM, transgender women, and transgender men was noted in some studies (Table 2), while others suggest low awareness in these populations (Table 2). However, several studies have more consistently demonstrated lack of awareness of PrEP among other populations at risk of HIV acquisition, including Black MSM, PWID, younger individuals, and communities in the Deep South (Table 2). Even among individuals aware of PrEP, limited knowledge about PrEP (i.e., if they have questions or concerns about it) can prevent PrEP initiation [20].

Lack of PrEP awareness has also been observed among people living with HIV, as was reported for 66% of participants (N = 137) surveyed in a Miami public hospital [21]. This is concerning, as these people living with HIV would be unable to advise their partners about PrEP [21]. In that same study, once they knew about PrEP, 86.0% of respondents reported that they would encourage their partners to use it [21].

Knowledge and awareness of PrEP among healthcare providers are also crucial for successful implementation [22] and can directly impact prescribing rates. In a study of local health departments in North Carolina, lack of PrEP awareness and knowledge among health department staff was cited as one of the most common reasons for not prescribing or referring individuals for PrEP [23].

While one 2018 study of New Jersey healthcare workers (including administrators, prescribers, social workers, and nurses) demonstrated a high level of PrEP awareness, at 91% [24], other studies suggest inadequate knowledge or awareness among some healthcare professionals/providers (Table 3). For example, 60% of 271 US nurse practitioners reported no prior PrEP training or education [25], while 58.3% of 12 Florida healthcare providers had read the CDC’s PrEP clinical practice guidelines, and only 41.7% could identify correct PrEP prescribing recommendations [26].

There are clear differences in awareness and knowledge within the healthcare professions. Only 65% of licensed medical providers surveyed in Washington State in 2016 (N = 735) had heard of PrEP, with younger healthcare professionals and those with a medical degree more likely to be aware of PrEP than older healthcare professionals and those with other training backgrounds [27]. There was also a disparity in awareness according to specialty; all infectious disease specialists surveyed had heard of PrEP, compared with around three-quarters of board-certified family medicine and internal medicine practitioners and around half of obstetrics/gynecology and pediatric practitioners [27]. Similarly, in a study of 53 family physicians, 71% had no/limited knowledge of PrEP treatment guidelines [28].

This disparity in awareness and knowledge between different healthcare professionals is important when considering the setting in which PrEP should be prescribed. Primary care doctors and generalists often consider PrEP to be an issue for HIV specialists [29, 30]. However, while infectious diseases specialists have knowledge of PrEP and the most experience in HIV care, they usually do not provide care for HIV-negative individuals who may benefit from PrEP; in fact, primary care physicians are more likely to come into contact with such individuals [29, 30]. This creates a “purview paradox” in which each group of healthcare professionals believes that the other is best equipped to provide PrEP [29, 30]. One study interviewed 30 healthcare professionals, including 17 providers who worked in a setting specializing in the care of HIV-positive individuals, on topics including who should be responsible for prescribing PrEP [29]. Both HIV specialists and primary care providers thought that primary care settings were a good site for provision of PrEP, as this is where people at high risk for HIV could be identified. However, there were concerns about a lack of specialist knowledge and bias in the primary care setting, with one HIV specialist stating about primary care: “They have minimal knowledge, and even though they may be treating some people, have probably some prejudice, or at least ambivalence.” It was felt that more training would be needed for primary care settings to offer PrEP.

Specific knowledge about PrEP medication, particularly how they work and the potential side effects, have also been highlighted as critical aspects for provision of PrEP by healthcare professionals [29]. Reluctance to prescribe PrEP may stem from provider misconceptions, such as concern that poor adherence may result in development of resistance [24, 31] despite the fact that clinical evidence to date suggests that HIV drug resistance with PrEP use rarely occurs [32, 33].

Some individuals who would be considered, by objective risk assessment, to be at risk for HIV perceive their own risk to be low. This can create another potential barrier to PrEP uptake, albeit with some conflicting evidence. One study has shown that some HIV-negative individuals at risk of infection (including MSM and PWID) perceive themselves to be at risk, are aware of PrEP, and show greater interest in using it than those without these risk factors [19]. However, many other studies have reported several demographic populations at high risk of HIV perceiving themselves to be at low risk, as summarized in Table 4. This is illustrated by data from a study of 5606 Philadelphia residents undergoing rapid HIV testing, where the investigators categorized 71.6% of men and 60.0% of women as moderate/high risk; in contrast, only 56.8% of men and 8.3% of women perceived themselves to be high/moderate risk [34]. Populations reported to have low perceived risk include some MSM, despite their disproportionate HIV risk [8], and women at increased risk of HIV acquisition including Black women, women experiencing gender-based violence, and women involved in the criminal justice system [8, 35‐37]. One study also highlighted “lack of concern about HIV” as a barrier to PrEP uptake in adolescent and young adult transgender men and women [38].

Another related individual-level barrier to PrEP access is low prioritization, which may be multifactorial. Prioritization may be a consequence of low HIV risk perception [39], substance use [40], or other behavioral health concerns [41]. In the USA, HIV prevalence is higher among people with serious behavioral health challenges (e.g., recurrent major depressive disorder, bipolar disorder, psychotic disorder, or comorbid mood disorder) compared with the general population [41‐43]. Social factors related to poverty that limit women’s access to antiretroviral therapy [44] may also impact PrEP prioritization: a 2017 review noted that “unemployment, unstable housing, and food insecurity may render accessing PrEP and taking PrEP as unimportant if women are unable to fulfill their basic needs for food and shelter” [45]. Another setting in which accessing PrEP may be deprioritized is for MSM who are released from incarceration: one study participant stated, “When you go home you have so much to do… you have to go back to welfare to get food stamps… so much different stuff… you’re not really going to be thinking about ‘I’ve got to go to the doctor’s [office] right away to get my PrEP’” [46]. Competing priorities have also been identified as major barriers to healthcare in general among homeless adults, for whom meeting basic needs for food, shelter, and safety outweigh healthcare needs [47].

PrEP implementation may also be reduced as a result of insufficient ascertainment of HIV risk by healthcare providers. In a survey of advanced practice nurses in Indiana, their comfort with discussing/prescribing PrEP was about 80% with gay or heterosexual couples in a monogamous relationship with one partner living with HIV infection, about 70% for PWID, and 60% for MSM who did not indicate their relationship status [48]. In a survey of health directors in North Carolina (N = 56), a perceived lack of suitable PrEP candidates was reported by 26% of respondents from departments not prescribing or referring individuals for PrEP [23]. Recently, a paradox concerning perception of risk and willingness to prescribe has been noted in an online survey completed by 111 medical students [49]. Results showed that willingness to prescribe was inconsistent with patient risk, with fewer students willing to prescribe PrEP if the patient was engaging in riskier behaviors such as not using condoms or having multiple partners. This was attributed to misconceptions about the effectiveness of PrEP and to personal biases related to sexuality and sexual orientation.

Social stigma perceived and/or experienced by individuals at risk of HIV is a major barrier to PrEP use (Table 5). This may stem from historical stigma surrounding HIV/AIDS (both the disease itself and being a member of a group considered at risk, i.e., sexual, gender, racial and/or ethnic minority); for example, transgender women in one focus group had concerns that by taking PrEP they would be mistakenly identified as HIV-positive [50]. It may also be stigma relating specifically to PrEP. The latter is largely attributable to “PrEP shaming”—the belief that PrEP users engage in reckless sexual behavior—and was a topic of much debate following the labeling of PrEP users as “Truvada whores” in 2012 [51, 52]. The evidence summarized in Table 5 suggests that PrEP stigma persists: participants from several studies reported experience of PrEP-related stigma that manifested in a number of ways, including stereotyping, rejection, and discrimination (including homophobia, transphobia, racism, and sexism), all of which were identified as barriers to PrEP use (Table 5).

The social stigma experienced by individuals may be compounded by PrEP-related stigma at the healthcare provider level. Some providers have been concerned by an increase in sexual behavior by PrEP users due to their perception that their HIV susceptibility is decreased, known as “risk compensation,” and this may foster reluctance to prescribe PrEP [53‐56]. A survey of 266 primary care physicians found those who had never prescribed PrEP or referred one of their patients for PrEP were more likely to believe that PrEP use would lead to risk compensation compared with those who had adopted PrEP (prescribed/referred) [53]. In a survey of 573 providers in the USA and Canada, risk compensation was also identified as a reason for providers not prescribing PrEP. Respondents were concerned that PrEP could create a “false sense of security,” and that if individuals would not use condoms then they would not use pills. Assumptions made by providers impact their perception of the likelihood of risk compensation. One study found medical students to stereotype Black MSM as more likely than White MSM to engage in increased condomless sex when on PrEP. This racial bias was associated with reduced willingness to prescribe PrEP [57].

Implicit racial and ethnic bias by healthcare professionals in the USA is well documented and can impact treatment decisions. One systematic review identified 15 studies that assessed implicit bias by healthcare professionals; 14 of these studies reported low-to-moderate levels of racial/ethnic bias among healthcare professionals. This implicit bias was significantly related to treatment decisions, patient–provider interactions, adherence, and, critically, patient outcomes [58]. A second systematic review found that 31/37 eligible studies reported racial/ethnic bias among US healthcare professionals, and of 14 studies that related bias with outcomes, six related higher implicit bias with treatment disparities [59]. Further, according to the 2011 “Report of the National Transgender Discrimination Survey” of 6540 transgender and gender non-conforming people across all 50 states, one-fifth reported being refused care, and almost one-third had been subject to harassment in a healthcare setting [60]. Beyond the individual provider level, there are also systemic biases: a widely used algorithm in US healthcare systems was found to exhibit significant racial disparity [61]. For patients assigned the same risk level by the algorithm, in reality, Black patients had increased signs that their medical condition was not controlled, compared with White patients with the same condition. This bias arose because the algorithm made predictions based on cost, rather than illness, which reflected spending inequalities for Black and White patient communities. It is unsurprising, therefore, that there remains a significant level of distrust of healthcare systems among some patient groups.

Distrust of healthcare providers/systems was identified as a key barrier to PrEP uptake (Table 6), particularly in populations with disproportionate HIV risk. As noted previously, feelings of distrust may be attributed to social stigma at the provider level; in a number of studies, participants were alienated from their healthcare system as a result of experienced and anticipated discriminatory judgment from providers in the form of racism or homophobia (Table 6). Furthermore, there have been a number of malign events in the US medical establishment that have led to distrust in the healthcare system, particularly for Black communities (e.g., the Tuskegee syphilis study, the case of Henrietta Lacks, and the 1946–1948 Guatemalan sexually transmitted disease experiments) [62‐65]. Medical distrust can also manifest as conspiracy beliefs; such beliefs have acted as a barrier to HIV prevention in the USA for years, with high prevalence within some Black communities attributed to historical racial discrimination [66‐68]. A similar pattern seems to be emerging with respect to PrEP. In a survey of Black and White MSM and transgender women who have sex with men (N = 264), conspiracy beliefs related to PrEP were endorsed by 42% of the population and were more frequently reported by Black than White participants. These beliefs included “The CDC cannot be trusted to tell gay communities the truth about PrEP” and “When it comes to PrEP, drug companies are lying and taking advantage of us” [68]. Other studies support high prevalence of HIV conspiracy beliefs among Black MSM in the USA, one of which reported a lower intention to adopt PrEP among those with a conspiracy belief [69, 70].

Finally, some patients may also have doubts about the validity of clinical data for the use of PrEP in specific patient groups. Black MSM, cisgender women, and transgender women have been reluctant to participate in clinical research, and consequently are underrepresented in clinical trials [71‐73]. One study found that lack of data on PrEP in specific populations was a barrier to PrEP uptake [50].

At the individual level, there are simple logistical constraints to accessing PrEP, exacerbated by socioeconomic inequalities. For example, individuals may experience difficulty in getting to the clinic [74] due to lack of transportation [46] or time constraints [75, 76]. A 2016 National Survey on HIV in the Black community found that 38% of 787 participants were more than one hour’s drive from a PrEP provider. People living in regions with higher PrEP clinic density were found to be significantly more willing to use PrEP [77]. Individuals at risk may also lack access to providers where PrEP is routinely offered [78], or may not have access to medical care of adequate quality, such as lesbian, gay, bisexual, transgender, and queer (LGBTQ)-sensitive care [79].

PrEP access by individuals at risk may also be impeded by barriers at the healthcare system/provider level [80]. Many of these are logistical barriers present in the healthcare system, such as pharmacy impediments (e.g., difficulty having prescriptions filled) [20, 81], lack of formal prescribing protocols [82], or absence of service provision in certain geographic locations [23, 82, 83]. For example, in a county-level analysis, the Southern region of the USA was found to account for only one-quarter of PrEP-providing clinics, despite representing over half of all new HIV diagnoses. Of note, the disparity in PrEP clinic density in Southern USA also contradicts need in terms of underrepresentation in areas with lower income, higher Black and Latinx/Hispanic populations, and less insurance coverage [82]. Another barrier to PrEP access at the healthcare system level is limited delivery of PrEP to difficult-to-reach populations, such as PWID and homeless individuals, on account of inadequate infrastructure, which will need to be addressed through innovative strategies [83, 84].

Financial concerns have been identified as common barriers to PrEP use across most populations at risk, including MSM, PWID, cisgender women, transgender women, young people, and homeless people (Table 7).

In addition to the studies highlighted in Table 7, media reports of insurance companies denying coverage to HIV-negative individuals who use PrEP [85, 86] and employers excluding PrEP from their insurance policies [87] have highlighted further barriers to accessing PrEP.

Patient concerns over insurance and ability to pay may in turn impact healthcare provider willingness to prescribe or discuss PrEP. For example, in one study of Washington State medical providers, while concerns about PrEP cost were frequent (43%), providers felt very (27%) or somewhat (45%) uncomfortable discussing cost and insurance issues [27]. In another study, low cost/insurance coverage was a facilitating factor for PrEP prescription by physicians providing primary care to adolescents (13–21 years old) [31]. Furthermore, cost may be a factor in negative provider attitudes toward PrEP, with some dismissing the preventive therapy as an “expensive condom” [55].

A cost-related barrier to uptake of PrEP may also be lack of knowledge around co-pays, or the availability of financial assistance, i.e., how to find programs and, once found, how to navigate the program requirements [88]. Thus, patient concerns around cost are both a reflection of misinformation in general communities, as well as lack of knowledge and misinformation from the providers themselves.

Another barrier to PrEP use is the experience and/or anticipation of PrEP side effects and/or medication interactions. Many studies, in various demographic populations, have captured concerns around short- and long-term safety of PrEP among individuals at risk (Table 8). Safety concerns were also reported in a large study at a New York City health center focusing on sexual and general health for LGBTQ communities; of 1208 PrEP users, 783 reported barriers; 67 reported side effects as a barrier to PrEP use, nine of whom stopped taking PrEP [20]. In addition, transgender individuals have specific concerns regarding PrEP and interactions with hormonal treatment [50, 89‐91]. Finally, although there are no data in the literature to quantify the actual impact on PrEP uptake, anecdotally there are concerns that misleading lawyer advertisements about lawsuits concerning F/TDF in the USA may play into patients’ concerns around PrEP side effects, leading them to discontinue or refuse PrEP medication [92]. Similarly, discussion of side effects on social media platforms could influence perceptions about PrEP and limit uptake [93‐95].

Provider concerns around PrEP side effects and safety may impact their prescribing practices, exacerbating barriers to PrEP use. This barrier is closely linked with knowledge about PrEP and understanding of the benefit/risk profile. A number of studies identified provider-level stigma with respect to PrEP safety; concerns around side effects/adverse events have been linked with negative attitudes toward PrEP and reduced intention to prescribe it [53, 55, 96, 97]. This is supported by a study of attitudes toward PrEP among physicians providing primary care to adolescents. Among 38 physicians who were interviewed, only 37% reported being somewhat or very familiar with PrEP, and concerns around side effects were identified as a barrier to PrEP use [31]. Similar findings were reported in a survey of internal medicine residents (N = 48), of whom 22% were unaware of PrEP and 62% had fair or poor awareness of side effects. PrEP was considered effective or safe by only 78% or 66% of participants, respectively [98].

Importantly, several of the key barriers to PrEP uptake discussed here have also been reported to hinder continued PrEP use (persistence). A study of 7148 individuals who initiated PrEP at a national chain pharmacy in the USA reported only 56% persistence in year 1, 63% in year 2, and 41% from initiation to year 2, with the lowest persistence in women and individuals aged 18–24 years. Factors predicted to contribute to PrEP cessation included financial barriers, changes in perceived risk, and difficulties accessing healthcare services [99]. Overcoming barriers to PrEP uptake may therefore have a concurrent positive impact on adherence to PrEP.

Clinical trials and data demonstrating recent decreases in the frequency of new HIV diagnoses in areas of the USA where PrEP uptake has been greatest support the effectiveness of PrEP as an HIV preventive strategy [2‐4, 100, 101]. In this review, key barriers to PrEP uptake were identified, including knowledge/awareness of PrEP; perception of HIV risk; social stigma; provider bias and distrust of healthcare providers/systems; lack of access to medical care; lack of access to (or awareness of) financial assistance options; and PrEP side effects and medication interaction concerns (Table 1). The barriers described have tended to be observed in populations at greatest risk with the lowest PrEP uptake, and may also originate at the provider level. Furthermore, barriers that prevent uptake are not universal, and can be population-specific, exacerbated by co-prevalent syndemic conditions such as racism, homophobia, poverty, inadequate education, and behavioral health issues. The findings presented here have also been identified by others, who have noted similar common barriers overall [102‐104] and in population groups at highest risk [105‐112].

Improved education or training of individuals at risk and providers will be essential in overcoming a range of barriers to PrEP uptake. To raise awareness and uptake of PrEP among individuals at risk, delivery of brief educational sessions for visitors to sexual health clinics could be an effective approach [113], as could provision of online resources such as those developed by the New York City Department of Health and Mental Hygiene [114] and The National Lesbian, Gay, Bisexual and Transgender (LGBT) Health Education Center at the Fenway Institute [115]. Social marketing campaigns also have the potential to reach millions of individuals, as demonstrated by the PrEP4Love campaign in Chicago [116]. However, despite the well-documented need to increase awareness of PrEP, a recent systematic review found that very few ongoing studies were addressing this need, particular noting a paucity of research on educational interventions targeted at cisgender women, transgender women, transgender men, PWID, and in Southern regions of the USA [117].

Education may also instill trust in healthcare providers/systems among individuals at risk. For example, improved accessibility and credibility of HIV prevention messaging in minority subpopulations has been proposed as a strategy to negate the impact of PrEP-related conspiracy beliefs [70]. Social media-based, peer-led interventions could also confer a significant population-level impact on PrEP uptake among young Black and Latinx individuals by addressing issues such as knowledge/awareness, attitudes, stigma, and treatment access [118]; similar interventions could successfully reach transgender women and MSM. Counseling on the benefits of PrEP, and providing information and reassurance on the risk and monitoring of short- and long-term side effects, may also improve adherence to PrEP [119].

It is also imperative that educational interventions are targeted to primary care providers, including training to increase PrEP knowledge [120] and to alleviate concerns regarding PrEP safety [98]. Concerns around risk compensation (or an increase in risk-taking behaviors among individuals at risk prompted by a decrease in perceived HIV risk) appear to be one factor that can cause reluctance among some healthcare providers to prescribe PrEP to eligible patients [53]. While several studies have reported risk compensation behavior in individuals receiving PrEP [121‐123], the balance of evidence suggests that patients who are eligible for PrEP inherently have a high baseline risk for STIs, which remains high following initiation of treatment with PrEP [88, 124‐128]. Even if risk compensation does occur in some individuals or populations, related concerns do not justify withholding PrEP from people at risk for HIV infection [56]. Consistent with this notion, it has been proposed that PrEP be viewed as an opportunity for improved STI control [124, 129], whereby an increase in detection rates due to more frequent STI testing, with potentially earlier diagnosis and treatment, may counteract or surpass any negative effects of risk compensation [130]. Nevertheless, patients receiving PrEP should be provided with support for risk-reduction behaviors [33]. Similarly, misconceptions around the development of treatment resistance may also account for the reluctance of some providers to prescribe PrEP [24, 31]. However, there is little evidence supporting the development of treatment resistance with the use of PrEP medications. The number of reported cases is extremely low, with the majority occurring in individuals with undiagnosed HIV infection or during sporadic unsupervised use [32, 33, 131], thus highlighting the importance of testing for HIV prior to PrEP initiation and regularly during use of PrEP, per clinical guidelines [33].

Education targeted to primary care providers has been shown to be effective: after an educational intervention, the proportion of participants (internal medicine residents) who believed PrEP was safe increased from 66% to 92% and the proportion who believed it was effective increased from 78% to 94%. Before training, only one-third of participants were likely to prescribe PrEP in the next 6 months, which increased to two-thirds after training [98]. Healthcare professionals wishing to prescribe PrEP and who want to learn more about its implementation can refer to current CDC/US Public Health Service (USPHS) clinical guidelines for comprehensive information on the use of daily oral antiretroviral PrEP to reduce the risk of acquiring HIV infection in adults [33]. Complementary information can also be found in the World Health Organization implementation tool for PrEP of HIV infection [132] and the US Preventive Services Task Force Recommendation Statement on PrEP [133, 134]. A summary of guidance for implementing PrEP in clinical practice is provided in Table 9.

Training may also be employed to improve cultural humility [104] and to overcome the potential impact of implicit bias, stereotypes, and anticipated risk compensation on willingness to prescribe [135]. However, to truly address bias entrenched in the healthcare system, changes need to be made at a societal level. The ultimate aim should be that the healthcare community workforce adequately reflects the populations it treats; programs that increase the number of Black, Latinx, and LGBTQ healthcare professionals are needed.

Some individual-level barriers to access, such as not knowing where to get PrEP [74, 136], should be relatively straightforward to address through improved communication with individuals at risk. However, improving access to PrEP will require innovative approaches to delivery of care. It is important that these strategies extend PrEP outreach by engaging a diverse range of providers, including those from non-traditional settings such as pharmacies, mental health clinics, substance use clinics, emergency rooms (ERs), HIV testing centers, correctional institutions, and community-based organizations [137]. For example, integration of HIV screening into ERs has been highly successful [138]. This and the apparent willingness of individuals who are at risk to accept PrEP from ER providers suggest that ERs could provide a setting to facilitate quick connections with PrEP providers [137]. For non-emergency settings, pharmacies should play an important role in PrEP implementation in the community [104]. The One-Step PrEP^® program, a pharmacist-managed approach that allows PrEP access following a single patient encounter, has been shown to be logistically and financially feasible, with positive responses from individuals seeking PrEP [139, 140]. Between March 2015 and February 2018, 695 patients initiated PrEP via the One-Step PrEP^® program and 98% had a zero-dollar patient responsibility per month. The dropout rate was 25%, and although 207 sexually transmissible infection diagnoses were made, no HIV seroconversions were reported [141]. State legislation, such as California Senate Bill 159, which allows pharmacists to provide PrEP medications without a prescription, may further expand pharmacist-led PrEP efforts and access in the USA. Integration of mental health screening into HIV healthcare has also been proposed as a strategy to improve HIV prevention [41]. Regardless of treatment setting, the development of stronger guidelines and policies for PrEP providers [97], along with the establishment of partnerships and effective communication between medical and social service providers [102], is needed. The World Health Organization reported that one of the critical enablers for programs to prevent and treat HIV was addressing basic needs, such as shelter, food, hygiene, childcare, recreation, and employment [142]. PrEP prevention programs targeted to certain populations may need to collaborate with programs and agencies who can provide this support.

Leveraging technology can make PrEP accessible to more patients; PrEP uptake may be supported by app-based delivery models such as TelePrEP, which connects individuals to a PrEP provider using a phone or computer [14, 143]. Similar approaches designed to reduce the patient and provider burden may also encourage PrEP persistence. As an illustration, the “PrEP@Home” model, designed to decrease monitoring by replacing quarterly PrEP follow-up visits with home care, was found to be acceptable by participants in a pilot study, and was in demand for future use [144]. This approach could be especially valuable to those without access to transportation [144] or those affected by the stigma of HIV. A pharmacy-based TelePrEP model was implemented in a large county hospital in Atlanta in February 2018: 41 out of 44 patients who started PrEP (93%) remained on PrEP in 2019 [145].

Among the easily surmountable barriers to PrEP uptake may be treatment cost and insurance coverage. While there is evidence to support cost as a perceived barrier to PrEP uptake for those who present for PrEP, the actual scale of this problem may be limited. A recent independent study of nationally representative data, including authors from the CDC, demonstrated that fewer than 1% of the individuals with indications for PrEP required financial assistance for both PrEP medication and clinical care [146]. An additional 7% required financial assistance only for PrEP clinical care (not PrEP medication). Thus, only a small number of patients were not financially covered for clinician visits or laboratory tests, and an even smaller number had no coverage for medication and clinical costs of PrEP care [146]. Regardless, there is a proportion of patients, albeit small, with an unmet need for financial assistance in PrEP care. Efforts of the US Department of Health and Human Services’ “Ready, Set, PrEP” program may help to address the unmet need in this population through provision of PrEP medication at no cost to qualifying recipients. This initiative is a component of the US government’s wider plan to “End the Epidemic,” which aims to reduce new HIV infections in the USA by 75% in 5 years and by 90% by 2030 [147, 148].

Starting in 2021, on the basis of the Affordable Care Act, private insurers will be obliged to cover PrEP as a result of the intervention receiving Grade A recommendation from the US Preventive Services Task Force [133, 134]. In addition, 2019 saw the introduction of the PrEP Access and Coverage Act to the Senate, which would require all private and public insurance plans to cover the costs of accessing PrEP [149]. Despite this, addressing the financial barriers to PrEP will require affordable and high-quality insurance policies that are ubiquitously accessible to individuals at risk throughout the USA [104]. For example, dedicated PrEP service reimbursement programs have been introduced in several regions to financially assist individuals at high risk of HIV acquisition, including those who are uninsured or underinsured [150‐152]. A number of states now offer PrEP DAPs (Drug Assistance Programs), which pay for medical and laboratory costs incurred by PrEP DAP enrollees [153]. However, there is not yet much overlap between the states offering PrEP DAPs and states with the highest need (states without Medicaid expansion). Efforts are required to ensure patients are better informed about the financial assistance options available to them. To this end, patients require services to help them navigate sources of support, identify financial help [80, 154], improve access to treatment, and encourage positive engagement [80].