Abstract
There is growing evidence that pre-exposure prophylaxis (PrEP) prevents HIV acquisition. However, in the United States, approximately only 4% of people who could benefit from PrEP are currently receiving it, and it is estimated only 1 in 5 physicians has ever prescribed PrEP. We conducted a scoping review to gain an understanding of physician-identified barriers to PrEP provision. Four overarching barriers presented in the literature: Purview Paradox, Patient Financial Constraints, Risk Compensation, and Concern for ART Resistance. Considering the physician-identified barriers, we make recommendations for how physicians and students may work to increase PrEP knowledge and competence along each stage of the PrEP cascade. We recommend adopting HIV risk assessment as a standard of care, improving physician ability to identify PrEP candidates, improving physician interest and ability in encouraging PrEP uptake, and increasing utilization of continuous care management to ensure retention and adherence to PrEP.
Men and transgender women (TGW) who have sex with men have a greater incidence of Human Immunodeficiency Virus (HIV) infection compared to TGW and gay, bisexual and other men who have sex with men (GBMSM) are at an increased risk from the HIV infection. Though pre-exposure prophylaxis (PrEP), a combination antiretroviral medication has been shown to reduce the risk of infection, the uptake is far below most national targets. To implement PrEP effectively, it should be addressed in the medical curriculum and the best practices in PrEP training employed in medical schools as part of the National HIV/AIDS prevention strategy to reduce the incidence of HIV.
Our review findings provide important information for clinicians, caregivers, healthcare administrators, and health policy makers as these findings highlight the need for the above-mentioned TGW and GBMSM to adhere to PrEP. Additionally, clinical faculty, residents, and physicians may work together to increase PrEP knowledge and competence in clinical settings by updating the graduate medical education curriculum and training methods.
Our findings may inform how to enhance physician ability to identify PrEP candidates, encouraging PrEP uptake and utilize continuous care management to encourage adherence to PrEP. We envision a greater role played by practicing physicians in mitigating the HIV infections through increased PrEP usage eventually contributing to enhanced patient care.
Background
Despite the decline in the number of individuals diagnosed over the past decade with Human Immunodeficiency Virus (HIV), approximately 50 000 new cases continue to be identified annually in the United States. 1 Pre-exposure prophylaxis (PrEP), a once-daily combination antiretroviral medication (tenofivir and emtricitabine) has been shown to reduce the risk of infection by between 44% and 86% 2 and, with greater medication adherence, reduction rates are found to be even higher.3,4 While it is estimated that 1.2 million people could benefit from PrEP, currently only 70,395 are taking this regimen. 5 This extremely low rate—under 5% (4.4%)—is of particular concern and may indicate a need to enhance primary care education to increase prescribing. The efficacy of PrEP among those with adherence was reported to be over 80%. 6
Since the inception of the HIV epidemic, men, and TGW who have sex with men have had higher rates of HIV infection in the United States7-9 compared with GBMSM. Despite accounting for as little as 2% of the U.S. population, men who have sex with men (MSM) make up 58% of people living with HIV/AIDS (PLWHA) nationwide, 10 and trends demonstrate that while infection rates are declining among heterosexual populations, they are either stable or reduced for all MSM with the exception of American Indian/Alaska Native and Native Hawaiian men who inject drugs among the MSM sub-population. 10 While few data are available on HIV disparities among transgender women who have sex with men, 2 available studies have reported higher rates among the male to female transgender (MTF) population than among heterosexual men or women.8,9 In the U.S., while women account for only 19% of all new HIV infections, Black women including multipartnering women are second only to MSM in new infection rates. 11 A summary of 4 national household surveys revealed that the percent of people who inject drugs (PWID) in the U.S. ranged from 0.24 to 0.59% across surveys. 12 The small sample size, exclusion of unstably housed, and incarcerated persons, missing key populations and self-report of data were recognized as limitations by Bradley et al. 12 Furthermore, PWID account for approximately 8% of new HIV infections in the U.S. 13 All of the aforementioned populations could benefit from PrEP and should be addressed in any curriculum designed to implement PrEP effectively.
The efficacy of PrEP as a preventive measure has been tested in multiple studies14-19 and meta-analyses20,21 and findings suggest that, when used consistently, PrEP results in significantly decreased rates of HIV infection. A meta-analysis study of PrEP efficacy confirmed that PrEP was equally effective for men and women.18,22,23 Nevertheless, physicians remain less likely to prescribe PrEP to women than to men. While no studies of PrEP for PWID have been conducted in the U.S., the Bangkok Tenofivir Study found a reduction in HIV infection of 49% to 74% 19 among PWID. However, uptake of prescribing PrEP for PWIDs has been slow, and may be in part due to lack of government support (providing needles and syringes, condoms, HIV testing, and counselling etc.) for PrEP with this population 24 and stigma related to injection drug use. 25
Though empirical support for the effectiveness of PrEP is well established, medication adherence mediates the impact the drug can have. Adherence rates have been found to vary widely across studies depending on how adherence is measured.26,27 In 3 studies where blood levels of Tenofovir were used to measure adherence, the HIV infection rates were strikingly lower (84%-92%) for people with the drug detected compared with placebo. 28 While some factors such as heavy alcohol use and younger age have been found to attenuate adherence, 28 other factors including partner support and increased perception of risk are associated with increased adherence. 29
In order for PrEP to reach its full potential in reducing HIV, those individuals at greatest risk must have widespread access. A predominant way to achieve this is by increasing the pool of willing and able prescribing physicians. While barriers to prescribing PrEP to at-risk populations have been noted in the literature,30-50 training primary care medical students appropriately to engage individuals at elevated risk in prescribing the medication is understudied, and recommendations for effective training are needed.
The aim of this scoping review was twofold: to determine: (a) what are the barriers to PrEP prescribing among practicing primary care physicians, and (b) what are the best practices in PrEP training employed in medical schools. The need to develop curricula that include PrEP training is directly in line with the National HIV/AIDS prevention strategy to provide doctors with the skills needed to reduce the incidence of HIV. The findings of this scoping review are organized using the PrEP cascade model, 31 and provide recommendations for both content and educational delivery methods.
Methods
Search Strategy and Study Selection
Four authors conducted a scoping review of articles retrieved from PubMed, Web of Science, CINAHL, and PsychInfo, using the following search terms: (HIV) plus any of the following: (Prevention OR Pre Exposure prophylaxis (PrEP) OR Biomedical HIV prevention OR oral preexposure prophylaxis OR Pre-exposure prophylaxis OR Healthcare provider OR primary care providers OR early adopters OR primary care OR health services research OR education, medical OR implementation OR Medical Field Training OR Training, Medical Field OR Studies, Medical Field). Title and abstracts were reviewed to determine relevance (whether the studies examine provider views of PrEP, or examine medical school training outcomes for PrEP) and articles were excluded due to the following criteria: (a) was a duplicate; (b) missing primary data (qualitative or quantitative); (c) did not discuss PrEP, reducing the total number of articles from 560 to 27.
The full texts of the remaining articles were examined and eliminated if they were commentaries and non-empirical, did not include US physicians, only included medical students or only addressed adolescent PrEP. Studies only of providers practicing outside the U.S. were excluded, as the barriers and facilitators to PrEP in other countries have been found to vary based on local context. Furthermore, studies examining provider views of PrEP for adolescents were excluded, as these barriers often pertain to consent and assent and involvement of family members and guardians that are often specific to individual state guidelines. Finally, commentaries and non-empirical articles were omitted. An additional 5 articles were excluded for relevance, reducing the number of studies from 27 to 22 total articles included in the review.
The full review process to demonstrate article exclusion is illustrated in Figure 1. Sixteen of the articles were cross-sectional surveys while a further 6 were qualitative interviews.
Schematic of literature search process.
Quality Assessment
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist 51 was employed to evaluate the 16 cross-sectional surveys. In previous studies the quality assessment tools have been summed and percentages calculated to indicate the degree to which the study had sufficient rigor to be included in a systematic review 52
For the 6 qualitative studies, the Consolidated Criteria for Reporting Qualitative Research (CORE-Q) checklist 53 was utilized to assess the quality of reporting. 53 These studies, while well reported, were missing key items from the CORE-Q, specifically in reporting relationships with the participants and reporting non-participation, including dropout rates. The setting, date of data collection, description of the subjects, study design, and quality scores from both STROBE and CORE-Q are presented, and summaries of the findings and conclusions from all the studies are presented in Table 1.
Summary of Systematic Review Findings.*
For studies prior to 2012, PrEP was prescribed as tenofovir-emtricitabine (TDF-FTC).
Results
Overall, we identified the following 4 overarching barriers to physicians prescribing PrEP: 1. The Purview Paradox (who should prescribe PrEP?), 2. Patient Financial Constraints, 3. Adherence and Fear of ART Resistance, and 4. Perceived Risk Compensation Behavior. The only identified facilitator to PrEP prescribing was physicians serving patients who were seen as high risk. We review each of these areas below.
Purview Paradox
Of greatest significance for primary care physicians is the purview paradox. This barrier refers to the fact that HIV specialists are the most informed and skilled in the delivery of antiretrovirals, whereas primary care physicians are more likely to encounter high risk HIV-negative persons in need of PrEP. 31 Primary care physicians often cited the lack of knowledge about antiretroviral medications as a barrier to implementing PrEP in general practice settings.37,40,47
Patient Financial Constraints
Additional barriers to prescribing included perceptions of the lack of financial resources to support prescriptions for PrEP patients,31,42,49 concerns about eliminating the consequences of high-risk behaviors,30,31,34,40,46,48-50 and the need for adherence monitoring.30,34,37,44-49 Prescriptions for PrEP can be expensive, and primary care physicians reported that patients that may benefit most from PrEP often do not have insurance or other means to pay for the prescription without financial assistance.31,42,49 Physicians also expressed concerns about risk compensation, or the idea that patients given PrEP may engage in more risk-taking behaviors as a result of feeling safer from infection30,31,34,40,46,48-50
Adherence and Fear of ART Resistance
Additionally, physician concerns over lack of adherence and subsequent development of drug-resistant strains of HIV were noted as affecting provider prescription behavior in several studies.30-32,34,37,44,46,48,49 In the studies that inquired about prescribing to PWID, lack of adherence specifically due to non-medical drug use was identified as a concern.36,37
Perceived Risk Compensation Behavior
Patients, who fall into elevated-risk group were found to be prioritized for PrEP prescription. An additional finding was a generally higher willingness to prescribe PrEP to sero-discordant couples and/or men identified as MSM. This may be due to a higher rate of these individuals having access to specialized clinics due to partner status or social network access. However, providers expressed less willingness to prescribe PrEP to other known high-risk groups: women with multiple sex partners; people with sexually transmitted infections; and PWID.10,12-14,17 The reviewed studies provide data primarily on barriers to PrEP. Little information regarding facilitators was found, and, to date, no studies provided data on approaches employed in medical schools to train students to prescribe PrEP.
Discussion
The findings of this review indicate the need to address barriers to PrEP provision among physicians practicing medicine in the United States. While knowledge of PrEP as HIV prevention was abundant, the numbers of physicians who had actually prescribed PrEP was low. Many studies reviewed up to 2017 showed <20% of physicians surveyed had ever prescribed PrEP.
Though there has historically been some confusion over the appropriate purview for PrEP, specialized clinics versus primary care, prescribing rates by primary care physicians have been rising. As noted in Figure 2, a national study of PrEP providers conducted annually from 2009 to 2015 41 found that HIV specialists are still most likely to prescribe PrEP, but over time, the number of primary care physicians prescribing PrEP has risen steadily. Mirroring this trend, research on barriers faced by primary care physicians to PrEP prescription have also risen.39,40 As these trends continue, it is clear that primary care medical education must address this important preventive tool.
PrEP prescription by provider type.
Many of the perceptions among primary care physicians limiting their use of PrEP have been found to be misapprehensions. Concern about patient financial constraints was widespread among physicians. However, a wealth of resources is available to support patients who are appropriate candidates for the regimen, including the Patient Advocacy Foundation, Gilead Sciences, and many state-based programs. 30 Both medical students and practicing physicians need information about these programs. Additionally, concerns regarding adherence were frequently noted. Adherence must be monitored and encouraged, and regular check-ups should be conducted to identify any adverse consequences from the medication30,34,37,44-49 To achieve this, providers may need to increase their level of non-judgmental patient communication regarding sexual risk.
Other topics that require non-judgmental communication are talking with people about changing desires to use PrEP and experiences with non-adherence. Further, while perceptions of risk compensation and the fear of the development of drug resistant strains of HIV due to inconsistent adherence were identified as major concerns among physicians, neither have been found in the literature of studies of PrEP.18,19,23,24
Patients in sero-discordant couples or self-identified MSM were noted as the most likely to be prescribed PrEP. However, in the U.S., HIV prevalence rates among women with multiple sex partners are second only to MSM, underscoring the potential for women with multiple sex partners to benefit from PrEP. 54 In addition, while currently PWID make up a small percentage of the number of new HIV cases, for the latest reporting year (approximately 9% including MSM who also are PWID), 1 in 23 men and 1 in 36 women who inject, respectively will be infected in their lifetime. 55 This rate clearly suggests the need for PrEP access among the PWID population. Even though the above-mentioned reports fall within the criteria for HIV PrEP developed by CDC and are currently being implemented in U.S., 55 the CDC guidelines have limitations in supporting PrEP uptake. 56 These limitations include incorrect categorization and confounding of sexual orientation, gender identity and risk behavior. 56 Education is also needed to ensure that physician stigmatization due to implicit biases of groups that are already marginalized does not create more barriers to health due to limiting PrEP access to these at-risk populations.
Recommendations for Addressing Physician-Identified Barriers
Considering the physician-identified barriers, we make recommendations for how physicians and students may work to increase PrEP knowledge and competence along each stage of the PrEP cascade. We recommend adopting HIV risk assessment as a standard of care, improving physician ability to identify PrEP candidates, improving physician interest and ability in encouraging PrEP uptake, and increasing utilization of continuous care management to ensure retention and adherence to PrEP.
The findings of this review are important to medical education, in that the key barriers to PrEP prescribing identified in the literature can be used to inform the development of PrEP delivery curricula for medical students. In order for PrEP delivery to be improved in real world settings, medical students will need training to identify appropriate candidates for PrEP based on risk assessment, patient data from electronic medical records, and patient preferences for the use of chemoprophylaxis. They will also need to increase their comfort in prescribing and monitoring patient adherence as well as their knowledge about patient assistance programs including: training in cultural humility to address bias towards high-risk HIV populations, practice taking an effective sexual history to identify patients that may be high risk, and overall training in what PrEP is and the benefits of PrEP in order for new physicians to be able to educate and answer patients’ questions surrounding PrEP. Full recommendations have been organized, outlined in Table 2, using the PrEP cascade model, 57 to provide medical educators a framework for teaching medical students and residents the requisite knowledge and skills to deliver PrEP in their future practices and for assessing the responsiveness of the health care system for PrEP delivery and adherence. Finally, suggestions as to how to integrate these skills into medical education curricula are offered.
Elements of the PrEP Cascade and Educational Recommendations.
Note. Adapted from Liu et al. 57
Assessing HIV Risk and Identifying PrEP Candidates
There is an increasing consensus that primary care is the appropriate venue for delivery of this preventive intervention. One key reason for this is that this setting will allow for maximum contact with at-risk patients. This is particularly true in practices that have large populations of MSM, transgender women, sero-discordant couples, women with multiple sex partners, young persons who have multiple partners, and PWID. Delivering PrEP in primary care settings will require provider comfort in obtaining thorough regular sexual histories, frequent HIV testing, and the delivery of HIV prevention messages delivered in culturally appropriate ways to a wider range of patients.
A key factor in the PrEP cascade is the employment of approaches demonstrating cultural humility in working with MSM, transgender, racial/ethnic minorities, and PWID individuals. The impact of intersectionality of race, gender, class, sexuality, and drug use also must be assessed. The outcomes will help individuals, who are discriminated because of layered identities including but not limited to race, gender orientation, social relations, power, oppression etc. Studies of lesbian, gay, bi-sexual, transgender, queer, and intersex (LGBTQI) individuals and PWID individuals seeking medical care have consistently found disparities in health outcomes.24,25,58-62 Patients who identify as LGBTQI frequently report discomfort discussing sex in the health care setting.58,59 One study of medical student responses to at-risk patients found that patient race/ethnicity can play a significant role in the likelihood of students identifying PrEP candidates. 60 Combating this will require increased training in sexual history taking, drug use history, cultural humility, and prevention counseling. In addition to the identification of individual risk behaviors, population health data may help identify patients that are part of broader social, sexual, and drug use networks. The addition of algorithms to electronic health records that trigger further screening of at-risk patients for HIV can also be used as a means to help students identify PrEP candidates.
Patient Interest in PrEP
Training in this area builds on risk assessment and identification strategies where physicians are trained to counsel patients effectively about PrEP and engage patients in the process.58-60 Whether training in brief motivational interventions that may assist patients in their increased risk perception and evince individual interest in PrEP is open for speculation.
PrEP Linkage
To facilitate an increase in use of PrEP in primary care settings, medical students must be exposed to training in LGBTQ and PWID affirming health practices. Shadowing PrEP delivery by residents and attending physicians can provide opportunities for medical students to observe PrEP prescribing. Training in this area could include opportunities to observe culturally appropriate language, care provision in a setting that is inviting to MSM, transgender people, and PWID, staff that is knowledgeable about the target populations, as well as opportunities for medical students to identify, reflect on, and address their own implicit and/or explicit biases regarding these populations.
PrEP Initiation
Additional training about antiretrovirals may be necessary for faculty members who are clinical preceptors if primary care is to be the venue for PrEP delivery. PrEP delivery can be discussed as a part of preventive counseling that includes other measures to protect against HIV, HCV, and other STIs. This approach addresses concerns regarding risk compensation, and allows the primary care setting to not only be the hub for PrEP prescription, but also for risk reduction for a broad range of risk-taking behaviors. For students, knowledge of antiretroviral medications can be discussed in year 1 microbiology courses. Pharmacy consultation may be a critical part of this element of training with attention on how resistance to medications is developed. Research describing the actual risk of mutation that weighs this against preventive value can be used in training to diminish this concern.61,62 Rotations through HIV clinics with physicians that have a vast knowledge of antiretrovirals (ARV) can expose medical students to ARV prescribing. This approach is expected to raise awareness of students about the necessary lab tests for PrEP, as well as identifying key issues in maintaining patients on PrEP.
PrEP Retention and Adherence
Medical training in the clinical years should include a focus on regular HIV testing, assessing PrEP side effects, providing ongoing support and risk reduction counseling, monitoring kidney function and conducting regular STI testing as parts of standard care of the PrEP cascade. Monitoring adherence, likewise, is a key element of effective PrEP delivery. Primary care residency training programs might focus on low cost methods (i.e., self-report) for monitoring adherence in the patient-centered medical home (PCMH) clinical settings. This step is expected to keep the PrEP cost low and available and promotes adherence. While self-report surveys have been found to over report adherence, the visual analogue scale has a strong concordance with unannounced pill counts in HIV treatment,63,64 but its validity with PrEP has not yet been demonstrated. On the other hand, dry blood spots which are highly accurate are very costly. As more accurate self-report measures and lower cost, urine and hair assays are developed, medical students should be trained in the most up to date protocols for monitoring patient adherence. Finally, because mental health and substance abuse are factors that affect adherence and retention, medical students should receive training in brief screening and intervention approaches to ensure these barriers do not affect medication adherence. These skills have broad applicability and can easily be integrated into the medical education curriculum in years 1 through 4 along with behavioral health content. The increasing connection between intravenous drug use, sexual risk behavior, and adherence to medication will make this increasingly salient for patients who are on PrEP. It is recommended that clinics, educators and programs ensure representation of people from key populations (TGW and GBMSM) in their cohorts, professional positions and student cohorts. Another recommendation involves working directly in community based, co-development training approaches.
Limitations
The review identified the barriers physicians face in delivering PrEP. At the time of the review (till 2017) no published papers on training efficacy were available. If PrEP is to be a viable preventive measure and realize its potential in ending the HIV epidemic, physicians must be trained to deliver PrEP, and barriers to prescribing PrEP must be addressed in training. Till 2017, few studies have examined the rate of at-risk patients seen by primary care physicians participating in the surveys. Nor do the physicians always know, as members of these groups may not readily identify themselves in a primary care setting. Without asking about physician sexual and drug use history taking, studies assessing rates with which at-risk patients are prescribed PrEP can provide only a rough estimate of the number of people who could benefit from PrEP. Additionally, 2 areas of the PrEP cascade have been neglected in most of the studies: patient interest in PrEP and linkage to PrEP. As a preventive measure, patients may opt out of PrEP even when they may be appropriate candidates, and only 1 of the articles addressed this crucial stage in the PrEP cascade. 47 Similarly, only 1 article addressed linkage to PrEP. 45 This element of the cascade may be obfuscated by the fact that physicians are not clear on the appropriate venue for delivery and thus may not see linkage as an issue that they must address. Another limitation of our study is that we have stopped our systematic review in 2017 as we had to wrap-up this study and move on to other medical education intervention efforts. Thus, we may have omitted some other studies that may have given us more current information on PrEP. Particularly, contemporary estimates of most training targets (domains) such as knowledge, willingness, comfort, attitude, adherence etc. may have changed in the recent 3 to 4 years since the cessation of our systematic review. Nonetheless, our effort laid a foundation on which further studies could be built to popularize PrEP as an educational intervention in under- and postgraduate medical education and clinical training.
Conclusion
The HIV epidemic will not be halted without innovative approaches that effectively curb HIV transmission rates. While PrEP has become 1 widely available solution, barriers to PrEP provision remain. We present findings from our scoping review as a means for collating physician identified (perceived and actual) barriers and offering up solutions and clarifications for misconceptions that pose as barriers. We recommend adopting HIV risk assessment as a standard of care, improving physician ability to identify PrEP candidates, improving physician interest and ability in encouraging PrEP uptake, and increasing utilization of continuous care management to ensure retention and adherence to PrEP. We hope our actionable recommendations inspire medical educators, students, and practicing physicians to play a greater role in attenuating the HIV epidemic through increased PrEP provision.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number UH1HP3048, titled “Academic Units for Primary Care Training and Enhancement.” This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government.