Understanding HIV Pre-Exposure Prophylaxis Questions of U.S. Health Care Providers: Unique Perspectives from the PrEPline Clinical Teleconsultation Service

Introduction

Despite a 56% increase in HIV pre-exposure prophylaxis (PrEP) uptake from 2012 to 2017 in the United States, ¹ of the nearly 1.2 million individuals at substantial likelihood of HIV infection, only 23% were prescribed PrEP in 2019. ^2,3 There are considerable disparities in PrEP use across demographic groups and U.S. geographic regions. ⁴ Health care providers' lack of PrEP knowledge, willingness to prescribe PrEP, and provision of PrEP prescriptions have repeatedly been shown to be key barriers to PrEP implementation. ^{5 –14}

In 2019, a comprehensive systematic review of published studies showed that among 18,265 providers, 68% had heard of PrEP and 66% were willing to prescribe PrEP; however, 37% had ever provided a PrEP consultation to a patient and only 24% had ever prescribed PrEP. ¹² Therefore, there is evident need for capacity-building among providers to strengthen the upstream drivers of the PrEP care continuum ¹⁵ (i.e., supporting providers to increase PrEP knowledge and comfort in prescribing PrEP) to influence downstream factors of PrEP uptake and persistence at the patient level.

Clinical consultation services, particularly teleconsultation services, staffed by HIV subject matter experts play a unique and important role and complement other HIV education and training activities. In addition to helping mitigate disparities in resource-limited settings and locations lacking or with limited availability/accessibility of clinical experts, such services may improve concordance of provider practices with evolving and evidence-based HIV care delivery, and potentially improve clinical outcomes for people living with HIV or with factors associated with HIV acquisition. National teleconsultation services may be of particular importance for clinics or health care systems without in-house access to clinical experts. Additionally, clinical consultants can identify knowledge gaps and provide innovative and/or pragmatic options to address clinical questions that are not yet addressed in national guidelines due to lack of data or lack of expert consensus.

By examining real-world clinical questions posed by health care providers, clinical consultants in turn have an opportunity to better understand the needs of providers—the gatekeepers of widespread PrEP provision—to improve their PrEP knowledge and comfort and identify specific PrEP-related issues for which research or guidelines are needed. Therefore, with the ultimate goal of improving PrEP provision, the objective of this research was to develop a collection of key PrEP-related topics by reviewing questions posed by real-world providers and teleconsultations provided by the National Clinician Consultation Center (NCCC) PrEPline (described below).

Methods

The NCCC is the first and longest running national teleconsultation service of its kind, which operates under the University of California, San Francisco's (UCSF) Department of Family and Community Medicine, and is supported by the U.S. Health Resources and Services Administration (HRSA) and the Centers for Disease Control and Prevention (CDC). The NCCC is a unique component of the national AIDS Education and Training Centers program and operates multiple national teleconsultation services for U.S.-based providers, including the HIV Warmline, ¹⁶ Perinatal HIV Hotline, ¹⁷ PrEPline, Post-exposure Prophylaxis Hotline (PEPline), Substance Use Warmline, and Hepatitis C Warmline.

The NCCC principal objective is to promote health equity by facilitating free, timely, evidenced-informed, and person-centered access to clinical subject matter experts through a model of direct clinician-to-clinician telephone- and web-based consultations and education. Since its inception in 1991, the NCCC has provided more than 300,000 on-demand clinical teleconsultations to individuals with a variety of health professional backgrounds and HIV experience levels. The NCCC consultants include multiprofessional medical, nursing, and pharmacy subject matter experts. Consultations are conducted in real time and documented by the NCCC consultants by entering de-identified data directly into the database either during or shortly after the call. Documented data include fixed data fields (e.g., caller name, profession, contact information) and open text fields including description of the case, caller's question(s), and consultant's response(s). The discussions are organized by the caller profile in the NCCC consultation database.

In the wake of the Food and Drug Administration's 2012 approval of the first PrEP regimen, the NCCC PrEPline was introduced in 2014 to offer clinicians access to an educational resource staffed by clinical subject matter experts who could respond to a wide variety of PrEP-related questions. The PrEPline receives questions related to PrEP eligibility, PrEP regimen selection and dosing strategies, PrEP initiation, baseline and follow-up laboratory testing, special circumstances (e.g., kidney or bone disease, pregnancy), and specific populations (e.g., transgender individuals and adolescents).

The NCCC consultation data are collected and stored in a secure, cloud-based customer relationship management platform. No protected health information is collected by consultants or stored in the consultation platform. Data analytics features of this platform were used to create reports capturing all PrEPline consultations during the 4-year calendar period from January 1, 2017, through December 31, 2020. We started with 2017 to align with the release of CDCs then updated PrEP guidelines. ¹⁸ PrEPline consultation call data were then exported to Microsoft Excel by one co-author (P.S.) for further analysis.

We used a qualitative content analysis approach in which clinical topics and subtopics were developed inductively through reading, interpreting, and discussing textual data. ¹⁹ Initially, one co-author (P.S.) reviewed a random sample of 40 calls to develop preliminary overarching clinical topics (e.g., laboratory ordering/monitoring and side effects) and subtopics (e.g., HIV viral load testing and testing window period) that captured the main themes and subthemes of the caller's inquiry and/or clinical case and their subsequent discussion with the PrEPline consultant. One co-author (P.S.) then trained three co-authors (A.S., N.J.M., and C.E.C.) to review and code all calls based on topic and subtopic and to iteratively refine the coding structure by identifying any topics/subtopics that were not originally captured by the first author.

Next, all the authors assigned up to three subtopics for each consultation. Additionally, the authors were trained to designate one of three levels of complexity for each consultation: (1) Level 1 or low complexity consultations (i.e., response to the question was available within the CDCs PrEP guidelines or other established medical guidelines); (2) Level 2 or moderate complexity consultations referred to discussions involving some complexity (i.e., cases with limited data to respond to the caller's question or questions that were partially addressed in CDC PrEP guidelines but required additional information to inform clinical decision-making); and (3) Level 3 or highly complex consultations (due to the absence of published data [i.e., no clear data/evidence-based guidance existed at the time to address the question, in some cases requiring PrEPline consultants to seek additional input from other PrEP researchers or clinical experts]).

Two co-authors (P.S. and C.E.C.) reviewed a random sample of 10% of categorized calls for quality assurance and to ensure consistency in coding across reviewers. One co-author (P.S.) used descriptive statistics to summarize caller demographic characteristics, call topics and subtopics, and the level of complexity.

Results

From 2017 through 2020, the PrEPline responded to a total of 1,754 clinical teleconsultation requests from providers across the United States (Table 1). There was a gradual increase in the percentage of PrEPline calls from 2017 (n = 414, 23.6%) to 2019 (n = 500, 28.5%) and a decrease in the percentage of calls in 2020 (n = 373, 21.3%). Most calls were from advanced practice nurses (n = 689, 39.3%) and physicians (n = 662, 37.7%), with a smaller percentage from other types of health care providers, including physician assistants (n = 131, 7.5%), pharmacists (n = 83, 4.7%), and registered nurses (n = 57, 3.2%).

Family Medicine (n = 372, 56.2%) and Internal Medicine (n = 96, 14.5%) constituted the majority of physician callers, whereas other specialists, such as Infectious Diseases (n = 80, 12.1%), called less frequently. The highest number of calls were from the Pacific region (n = 493, 28.1%), and the fewest number of calls were from the Southeast (n = 155, 8.8%), South Central (n = 124, 7.1%), and New England (n = 110, 6.3%) regions. The majority of callers indicated that they had ever prescribed PrEP (n = 987, 56.3%) and had at least one patient on PrEP (n = 884, 50.4%).

Questions regarding specific medication-based HIV prevention strategies composed the greatest percentage of cases (n = 931, 22.7%; Table 2). The most commonly discussed subtopics within this topic area included PrEP medication initiation (n = 379, 9.3%), followed by consultations around the concept of undetectable = untransmittable or “U = U” (n = 120, 2.9%), transitioning from post-exposure prophylaxis (PEP) to PrEP (n = 104, 2.5%), PrEP continuation (n = 100, 2.4%), and deciding between prescribing PEP or PrEP (n = 95, 2.3%).

Under the topic of PrEP laboratory ordering/monitoring, general questions about which laboratory tests to order/monitor before or during PrEP use (n = 598, 14.6%) were the most common subtopic. Questions regarding side effects and contraindications arose least frequently; within this topic, renal side effects of PrEP were discussed for 249 calls (6.1%) and infrequent side effects such as liver toxicity were discussed in 67 calls (1.6%). Overall, 57.9% of calls fell within the Level 1 complexity group, and smaller percentages were categorized as Level 2 (25.5%) or Level 3 (5.8%).

Specific questions regarding deciding between tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF; n = 118, 2.9%) or alternative dosing strategies such as 2-1-1 dosing (n = 87, 2.1%) were frequently asked in the “PrEP medication information and dosing strategies” topic. Nearly 51 (1.2%) questions were regarding discrepant HIV screening/testing results before or after PrEP initiation (i.e., inconclusive or indeterminate testing results that were inconsistent and/or did not denote a clear negative or positive HIV serostatus). Additionally, few callers (n = 11, 0.3%) asked about more complex concepts of presumptive antiretroviral therapy (ART) prescribing (i.e., the use of ART to cover both prophylaxis and treatment in the event of a recent exposure within the “window period” of HIV diagnostic testing) and PrEP “failures” (i.e., HIV acquisition in PrEP users; n = 10, 0.2%).

In addition to questions regarding the utility or efficacy of PrEP in cisgender women (n = 72, 1.8%) and adolescents (n = 68, 1.7%), questions related to other specific patient populations included PrEP for transgender women (n = 18, 0.4%), people who inject drugs (n = 17, 0.4%), transgender men (n = 8, 0.2%), older adults (n = 6, 0.1%), and other unique populations (n = 21, 0.5%) such as incarcerated people, people seeking prophylaxis against HIV-2, people with dysphagia, people with a history of bariatric surgery, or those on hemodialysis.

Discussion

This report provides unique insight on the types and complexity levels of clinical cases and questions posed to national HIV PrEPline consultants by frontline U.S. health care providers and helps describe the “real-world” landscape of clinical case scenarios and medical decision-making. While it was encouraging that a high number of advanced practice nurses and physicians used this service, the numbers of physician assistants, pharmacists, registered nurses, and other health care providers contacting the PrEPline were low. This may indicate a potential need for increased training and involvement of these professions in PrEP-related care. Specifically, given evidence of successful pharmacy-led PrEP services, ^20,21 training of more pharmacy and nursing providers may increase opportunities for PrEP implementation and access and team-based care.

Additionally, Family Medicine and Internal Medicine constituted a higher number of the physician callers compared with Infectious Diseases and other specialties. This may be in line with a key barrier to HIV prevention services known as the “purview paradox” whereby HIV specialists often do not see HIV-negative individuals and primary care physicians may have varying levels of experience and comfort with PrEP. ^11,13

Most PrEPline inquiries came from providers in the Pacific region, and fewer questions were from the South region. This pattern bares resemblance to data demonstrating lower PrEP to need ratio in the South compared with other regions. ⁴ Our observation may be due to higher adoption of PrEP in the Pacific region, the geographic proximity among regional providers to the PrEPline, and/or familiarity with UCSFs HIV-related services. It is important to note that the PrEPline is federally funded and available at no cost to all providers nationally; therefore, the use of PrEPline as a clinical resource can be integrated into PrEP training and educational material and PrEP academic detailing efforts across all U.S. regions. ²² The use of PrEPline may also be of particular value in rural areas of the United States where family medicine residency programs lack PrEP training and programs. ²³

Even though the responses to many questions presented to the PrEPline could be found within the established CDC PrEP guidelines (i.e., Level 1 complexity), there are opportunities for future iterations of the guidelines or locally disseminated PrEP clinical guidance to develop content that clearly and succinctly addresses commonly asked questions with practical guidance and clinical decision-making support (i.e., more user-friendly). For example, step-by-step instructions on transitioning from PEP to PrEP may be useful, and case-based learning may be an approach, which holds appeal for newer PrEP providers.

While some of the questions posed by 2017–2020 PrEPline callers have been addressed in the updated 2021 CDC PrEP guidelines, ^24,25 this study may inform future guidelines committee planning and PrEP research efforts by identifying areas that could benefit from additional clarification and investigation. Additionally, PrEP educators and trainers may wish to tailor information from the guidelines to make them optimally useful for providers. Finally, nearly one third of PrEPline callers asked clinical questions related to PrEP prescribing that required clinical judgment and extrapolation of data/practices from other areas of HIV prevention and treatment (i.e., Level 2 or 3 complexity). These data can offer providers and researchers a view of PrEP topics that would benefit from expert consensus around “best practices” and more research.

This study reflects the needs and questions of a self-selecting group of providers; however, despite this limitation, these data can aid the NCCC and other organizations in development of “Frequently Asked Questions,” PrEP toolkits, or “pocket cards,” as well as creation of more substantial PrEP clinical training materials for health care providers. Given an abundance of evidence suggesting that providers would be more willing to provide PrEP if empowered with additional training, ^26,27 these data can be used to develop such training materials and case discussions using commonly encountered, real-world clinical scenarios to improve providers' knowledge and comfort with PrEP initiation and continuation.

Given the successes of academic or public health detailing, these PrEP training materials and case discussions can be used to market PrEP directly to providers to address gaps in PrEP prescribing. ²² Finally, the widespread use of the PrEPline across the United States highlights the importance of accessible capacity-building services and programs and teleconsultation resources. Along with other innovations in PrEP care, such as mobile clinics, pharmacy-led PrEP delivery, PrEP coordinator-led PrEP delivery, mobile health and web-based technologies, social media platforms, and home collection of laboratory samples, ^{28 –32} the PrEPline is an example of how health systems may better incorporate new technologies in health care to make PrEP care less burdensome and improve care in a sustainable and cost-effective ³³ manner.