Perspectives on Injectable HIV Pre-Exposure Prophylaxis: A Qualitative Study of Health Care Providers in the United States

Abstract

The introduction of injectable HIV pre-exposure prophylaxis (PrEP) has the potential to significantly change the biomedical HIV prevention landscape. However, effective implementation will require health care providers to adopt, prescribe, and administer injectable PrEP within clinical settings. This study qualitatively examined challenges and benefit of injectable PrEP implementation from the perspective of health care providers. From April to August 2022, we conducted 19 in-depth interviews with current PrEP-prescribing health care providers in New York State, including 3 physician assistants, 5 physicians, and 11 nurse practitioners. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed to report semantic-level themes regarding injectable PrEP implementation. More than half of participants (61%) were aware of injectable PrEP; only 21% had experience prescribing it. Qualitative findings highlighted five themes. Three themes represented implementation challenges, including speculative concerns about side effects, appointment compliance, and practical and logistical considerations. The remaining two themes described benefits of injectable PrEP relative to oral PrEP, which included greater convenience and enhanced privacy. Findings from this qualitative study make significant applied contributions to the sparse knowledge on health care provider perspectives of injectable PrEP post-US Food and Drug Administration approval and their concerns and considerations regarding implementation in real-world clinical settings.

Introduction

In the United States, HIV prevails as a significant public health concern, with ∼36,000 people diagnosed with HIV and more than 1.2 million people living with HIV in 2021.¹ The introduction of oral HIV pre-exposure prophylaxis (PrEP) has dramatically changed the biomedical HIV prevention landscape, illustrating significant efficacy at preventing HIV acquisition.² However, uptake of oral PrEP has not met expectations; only 30% of people clinically eligible for PrEP received a prescription in 2021.³ The introduction of new modes of administration has the potential to increase PrEP uptake and accessibility. In 2021, the US Food and Drug Administration (FDA) approved the first ever long-acting injectable medication for HIV PrEP.⁴ Clinical trials have demonstrated injectable PrEP to be highly effective at preventing HIV acquisition when administered as a bimonthly, intramuscular gluteal injection.^5–7

The introduction of injectable PrEP has the potential to renew hopes for ending the HIV epidemic in the United States. Research has illustrated great interest in injectable PrEP among populations at an increased risk for HIV.^8–11 Among a community-based sample of sexual minority men, more than two-thirds (67%) of participants noted injectable PrEP as their ideal PrEP modality.⁸ Patient interest in injectable PrEP may be motivated by its potential benefits. Greater convenience,^12–17 improved adherence,^11,12,17,18 reduced pill burden,^9,12–15 and increased privacy^12,16,19 have been identified by patients as perceived advantages. Yet, this important advancement in HIV prevention is not without challenges.

Several qualitative studies have identified cost and insurance coverage,^12,17,20 frequency of injections,^12,16,21 side effects,^16,17,21 and dislike of needles^12–14 as potential barriers to patients using injectable PrEP. Further, results of a secondary analysis from the first unblinded year of the HTPN 083 randomized control trial demonstrated that injectable PrEP was associated with a higher incidence of dyslipidemia, hypertension, malaise, and proctitis compared to oral PrEP.²²

Effective uptake of injectable PrEP will also require that health care providers are knowledgeable about and willing to adopt, prescribe, and administer injectable PrEP within clinical settings. Currently, there is a dearth of literature examining injectable PrEP uptake from the perspective of health care providers post-FDA approval. A recent systematic review conducted from 2010 to 2021 on the values and preferences for injectable PrEP identified five studies from the perspective of health care providers.²³ Like patients, providers highlighted greater convenience, adherence, and confidentiality as benefits of injectable PrEP.^12,20,24 Challenges included costs associated with the medication and logistical challenges, such as limited staffing and resources, increased time, and limited financial support.^12,13,25,26

While previous research has provided valuable insights into the benefits and challenges of injectable PrEP from a clinical perspective, most studies were conducted with injectable PrEP as a hypothetical HIV prevention method, and few were conducted post-FDA approval. Further, current literature has noted important implementation considerations for injectable PrEP, including educating and supporting health care providers to provide injectable PrEP and addressing clinical barriers to its uptake.^27,28 As such, to maximize its prevention potential, a greater understanding of health care provider perspectives on injectable PrEP is essential for widespread clinical implementation. Thus, the overarching goal of this study was to qualitatively explore health care provider perspectives on injectable PrEP implementation within clinical settings.

Methods

Participants and procedures

From April to August 2022, we recruited potential study participants using the publicly available New York State Department of Health (NYSDOH) PrEP Voluntary Provider Directory. Health care providers were contacted through phone or email and screened for eligibility. Participants were eligible if they were (a) a health care provider with prescribing privileges in New York State, who had prescribed PrEP for at least 3 months, (b) 18 years or older, (c) able to read and write in English, and (d) willing to complete a web-based survey and qualitative interview. Eligible participants were emailed a study information sheet and invited to complete a qualitative interview.

Interviews were conducted in English by a trained research staff member through phone or Zoom. Before the interview, participants completed a brief survey assessing demographic and clinical characteristics. A semistructured interview guide was then used to direct discussion regarding knowledge, awareness, and perceptions of injectable PrEP implementation. Interviews occurred until data saturation was achieved, and no new information emerged. Participants received a $50 Amazon e-gift card. The University at Buffalo Institutional Review Board approved all study procedures with a waiver for written informed consent.

Data analysis

Interviews were audio-recorded, transcribed verbatim, and ∼42 min in length (range = 30–68 min). We conducted a five-phase thematic content analysis to report semantic-level themes.^29,30 First, three research team members (J.B., M.C., and S.P.) familiarized themselves with the data and developed an initial codebook. Second, two team members (J.B. and M.C.) applied the initial codebook and coded a subset of transcripts (n = 5).

The team members met regularly to iteratively revise the codebook and resolve coding discrepancies through discussion and mutual agreement.³¹ Third, the two team members applied the revised codebook and re-coded the initial subset of transcripts to ensure consistency and reliability. The two team members then independently coded the remaining subset of transcripts (n = 14). Finally, the three team members conducted a cross-analysis to identify themes through observed patterns in the qualitative data and selected representative quotes for each theme. We assessed the rigor and trustworthiness of the data using previously established criteria.³²

Results

Sample characteristics

Nineteen health care providers participated in this study, including 3 physician assistants, 5 physicians, and 11 nurse practitioners. The majority identified as female (79%) and non-Hispanic White (89%). Age ranged from 29 to 64 years (M = 42.7 years). More than half of the participants (61%) were aware of injectable PrEP; only 21% (n = 4) had experience prescribing injectable PrEP to patients. Additional participant characteristics appear in Table 1.

Table 1.

Participant Characteristics (N = 19)

Characteristics	n (%)
Age, M (SD)	42.7 (11.1)
Gender
Female	15 (78.9)
Male	4 (21.1)
Race
Non-Hispanic Black	1 (5.3)
Non-Hispanic White	17 (89.4)
Hispanic White	1 (5.3)
Sexual orientation
Bisexual	1 (5.3)
Heterosexual/straight	17 (89.4)
Not sure/questioning	1 (5.3)
Clinician type
Nurse practitioner	11 (57.9)
Physician	5 (26.3)
Physician assistant	3 (15.8)
Years of clinical practice, M (SD)	13.2 (9.5)
Aware of injectable PrEP	12 (63.2)
Prescribe injectable PrEP	4 (21.0)

PrEP, pre-exposure prophylaxis; SD, standard deviation.

Thematic analysis identified five themes describing providers' perspectives on implementing injectable PrEP in clinical settings. Three themes highlighted challenges to injectable PrEP implementation: (a) Speculative concerns regarding side effects, (b) appointment compliance, and (c) practical and logistical considerations. The remaining two themes represented benefits of injectable PrEP relative to oral PrEP: (d) Greater convenience and (e) enhanced privacy.

Speculative concerns regarding side effects

While providers themselves were not concerned about the side-effect profile of injectable PrEP, they noted that it may be a concern for patients. Providers discussed that patients may worry about experiencing side effects (e.g., injection site reaction, fever, fatigue) and fear not being able to stop taking the medication immediately, given its long-acting formulation. One provider said, “You can't stop it. Once it's injected, it's in your body. It's not like a pill where if you take it and you have side effects, you can stop it. With an injection, you're stuck with it until it wears off. I think that that's a concern with an injectable medication” (51-year-old physician assistant). Providers noted that this may deter patients from considering injectable PrEP as an HIV prevention option:

I think people are still a little leery of it being an injection and how if it makes them feel whatever way that is, but if it's in their body, they can't get it out… once they get this injection, if they don't like how it makes them feel they're kind of stuck until it just wears out… it's new and [people] just fear the unknown. (62-year-old nurse practitioner)

As stated by the previous participant, providers discussed how this reluctance may be related to the novelty of injectable PrEP. Another provider echoed a similar sentiment, “It [injectable PrEP] is newer, but it's been approved, yet some people may not want something that's newer. They might want something that has longer term data on it” (37-year-old physician).

Appointment compliance

One prevalent concern for providers was their patients' abilities to maintain the bimonthly appointment schedule. First, providers noted that using injectable PrEP requires a greater number of visits to a health care provider or clinic compared to oral PrEP. Providers discussed that this may not be ideal for patients who are relatively healthy and have not previously engaged with their health care at this capacity.

As one provider said, “it's frequent, so for people who are otherwise healthy and don't see a doctor frequently, it's not ideal” (37-year-old physician). Second, providers noted that their patients' busy schedules may make it difficult for them to comply with the treatment schedule. One provider drew upon their own busy schedule to highlight potential challenges that patients may face, “I work usually work five days a week, like how would I take an hour off every other month to go and get a shot somewhere? That seems like a pain and then having to coordinate travel or any plans around that shot with only a week on either end of flexibility” (35-year-old nurse practitioner).

Finally, others noted that some patients already have difficulty accessing transportation to attend their oral PrEP appointments. For these patients, increasing the number of appointments for injectable PrEP may make compliance difficult. One provider said, “Many people have transportation problems to get to the office, and then they no-show, or they might lapse on their [injectable] treatment, versus if they had it [oral PrEP] at home, they don't have to go anywhere” (62-year-old nurse practitioner).

Practical and logistical considerations

Providers highlighted several practical and logistical considerations that make implementing injectable PrEP challenging. Most providers described injectable PrEP as “expensive and complicated” (38-year-old nurse practitioner). Providing injectable PrEP in their clinics was often complicated by obtaining prior authorizations from insurance companies. The additional steps to obtain authorizations for injectable PrEP as a medical benefit compared to a pharmacy benefit strained clinic-related resources. This process was challenging as it differed from how providers have traditionally prescribed oral PrEP. When asked about implementation challenges, one provider described this phenomenon:

Having it [injectable PrEP] as a medical benefit instead of a pharmacy benefit, requires this whole other process that we're not used to. We're used to doing prior authorizations for pharmaceutical drugs, but the whole process for a medical benefit is almost like we're getting approval for somebody having surgery instead of just prescribing a medicine, which makes it more complicated and more time consuming… this whole process takes up time and effort of staff. That's the biggest barrier. (35-year-old nurse practitioner)

Another consideration for providers was the perceived time to administer the injection. Many providers acknowledged that a medication injected by a health care professional inherently takes more time and resources compared to writing a prescription for an oral medication. One provider compared the time commitment of injectable PrEP to oral PrEP:

“Having the resources to do it and time. With oral PrEP, it's just me that has to see the patient because I prescribe the prescription, send it to the pharmacy, and they're out the door. With injectable PrEP, I see the patient and then determine [if] they're a candidate, write the prescription, and then would have to either go draw up the injection, prepare it and then go back in the room and give the injection, or have one of my nurses do it if I have a nurse there that day. So there's more staffing involved and a little bit longer of an appointment making sure you have the resources to provide it like that full injection itself.” (30-year-old physician assistant)

Finally, providers discussed how limited staffing and resources may complicate scheduling and clinic flow. Given that patients would be coming to the clinic every other month, not having adequate resources to accommodate an increase in patient volume could make it difficult to establish an efficient workflow for injectable PrEP. As one provider stated,

Scheduling. Large part of it is scheduling right now, so getting patients in has been tough. Having them in every two months is a challenge. We just hired our newest nurse practitioner, and there is another one that just started, too. Hopefully with their assistance, we can open our schedules, but right now, that's one of the biggest barriers. (52-year-old physician)

Greater convenience

One benefit noted by providers was that injectable PrEP may be more convenient for patients. Many providers shared that injectable PrEP is “less work” because it removes the inherent cognitive burden associated with taking an oral medication. One provider said, “I think the ease of not having to worry about taking a pill every day, or remembering to take a pill, you just have to remember to come in the office for it, so, it could just be easier, because people don't really have to think about it in between the two months for their shots” (58-year-old physician).

The convenience of injectable PrEP was described as an attractive attribute for both patients and providers. For patients, it removes daily pill burden and nonadherence concerns. One provider said, “You don't have to mess with pills. …The real benefit of injectable medications, other than reducing pill burden, is that it completely removes human error” (41-year-old nurse practitioner). For providers, injectable PrEP gave them reassurance that a patient's protection against HIV acquisition was no longer dependent on adherence to oral PrEP, but rather an injection administered by a nurse or provider. One provider echoed this sentiment, “…They don't have to think about it every day. All they have to do is make their appointment and then rely on the nurse or provider or whoever is giving them their shot. It's just kind of out of their hands and less room for error” (30-year-old nurse practitioner).

Enhanced privacy

Another salient benefit expressed by providers was the ability for injectable PrEP to increase patient privacy. Injectable PrEP was described as “concealable,” given that patients would no longer need to have a physical pill bottle in their possession. As one provider stated, “A big part of injectables is the privacy of it and I think that patients are having high risk sexual behaviors, then I can see them wanting to not have pills out when they have people over or something like that” (29-year-old nurse practitioner). Many providers viewed this as a great benefit of injectable PrEP as it reduces the possibility that a friend, family member, or partner will find a prescription bottle and make assumptions about a patient's sexuality, sexual practices, or HIV status. One provider said,

[It's] the idea of privacy. If you're taking oral PrEP, then you have this medicine bottle in your cabinet, and then somebody looks at it and says, “Why are you on Descovy or Truvada? Isn't that for HIV?” They Google it and they're like, “Oh, it's for HIV. Why are you on an HIV medication? Are you HIV positive?” Versus if you just come into the clinic and get a shot every two months, then there's no evidence. There's more privacy. (41-year-old nurse practitioner)

Discussion

New PrEP modalities, such as injectable PrEP, have the potential to significantly advance HIV prevention efforts in the United States. Healthcare providers will play a critical role in the adoption, implementation, and uptake of injectable PrEP as an additional prevention option for people at risk of HIV acquisition. In this study of health care providers, five themes emerged, centering on the various challenges to injectable PrEP implementation and the benefits of using injectable PrEP relative to oral PrEP.

Providers in our study noted several challenges to injectable PrEP implementation. One challenge was that patients may not wish to use injectable PrEP because of side effects. For providers, concerns regarding side effects were mainly driven by the perceived difficulty of discontinuing injectable PrEP because of its long-acting formulation.¹³ While previous studies have identified side effects a potential barrier to injectable PrEP use,^16,17,21,33 ECLAIR trial participants reported relatively high tolerability with injectable PrEP; 66% of participants reported satisfaction with side effects and only 25% were dissatisfied with injection-related pain or discomfort.³⁴

Our findings suggest that side effect-related reluctance may be a result of the novelty of injectable PrEP. Research among women in the Women Interagency HIV Study described similar sentiments, as participants were apprehensive to use injectable PrEP due to its newness.¹⁶ This mutual concern highlights the need to educate providers about the safety and effectiveness of injectable PrEP and to train providers on how to successfully communicate these considerations to patients in an effort to support shared decision-making regarding PrEP uptake and use.^33,35

Another implementation challenge was patient compliance. Similar to health system stakeholders in Ontario, Canada,¹² providers described that bimonthly injections greatly increased the number of clinic visits required and were concerned that patients may initiate injectable PrEP, but not return for their next injection or STI testing. Patients have also echoed similar concerns, citing that injectable PrEP would take more time¹² and may be difficult to integrate into busy lives.²¹ Structural barriers, such as access to transportation, played a major role in providers' concerns regarding appointment compliance.

Transportation is consistently cited as a barrier to oral PrEP uptake and adherence.^36,37 Addressing transportation barriers to PrEP uptake and adherence is vital to maximize the prevention potential of injectable PrEP. Future research should examine accessible options for injectable PrEP administration and alternative strategies for PrEP-related STI testing. For instance, pharmacist-led programs³⁸ and at-home testing strategies³⁹ are highly acceptable and feasible among oral PrEP users; yet, the extent to which these strategies translate to injectable PrEP is unknown.

A recent review article described various practical and logistical concerns, such as time and financial support, as key considerations needed for the provision of injectable PrEP,²⁶ a sentiment echoed by providers in our study. Most notably, providers discussed insurance complications, time constraints, and limited staffing and resources as implementation challenges. Like previous work,^12,24,25 providers in our study were concerned about insurance coverage and costs. Difficulties obtaining prior authorizations from insurance companies were of particular concern. Despite guidance that injectable PrEP can be covered by insurance companies as a medical benefit, pharmacy benefit, or both,^40,41 providers recounted difficulties getting insurance companies to cover injectable PrEP, which complicated implementation efforts. Limited time, capacity, and resources were also voiced as implementation challenges. A common concern was the ability to provide injectable PrEP in clinics with existing staffing, time, and resource limitations.^12,24,42

Despite implementation concerns, providers described significant benefits of injectable PrEP relative to oral PrEP. Congruent with previous research,^12,14,15,24 providers noted that injectable PrEP would reduce daily pill burdens for patients, making injectable PrEP more convenient for patients. Providers were enthusiastic that adherence to injectable PrEP relied on a provider-administered injection, thereby reducing patient-related adherence challenges to daily pills,⁴² suggesting injectable PrEP may be a more favorable option for patients who struggle with adherence to oral PrEP.^12,18

PrEP stigma is documented as significant barrier to uptake and adherence.⁴³ Previous research has associated PrEP use with various negative assumptions and stereotypes about a patient's HIV status or sexual behaviors.⁴⁴ Further, PrEP stigma has been shown to be associated with decreased interest and uptake of PrEP among nonusers^45,46 and a driver of nonadherence and discontinuation among users.⁴⁷ Relative to oral PrEP, findings from this study suggest that injectable PrEP may assist with reducing PrEP-related stigma, a sentiment also noted by patients.²¹ For instance, providers described how injectable PrEP has the potential to increase privacy, given that adherence to the medication is confidential and inconspicuous, a finding echoed by health care providers^12,24 and patients^{12,13,16,48,49} alike. Our results coupled with previous work suggest that uptake of injectable PrEP could significantly reduce PrEP-related stigmas and stereotypes and may be more acceptable among patients who seek to conceal their PrEP use.

It is notable to mention that more than half of our sample were nurse practitioners in a state with full practice authority, which suggests that nurse practitioners play an integral role in improving PrEP uptake and access.^50–53 For instance, an analysis of scope of practice law classifications for nurse practitioners found that nurse practitioners in states with full practice authority were 1.4 times more likely to prescribe oral PrEP compared to nurse practitioners in states whose prescribing authority was dependent on a supervising physician.⁵¹

Further, a recent systematic review and meta-analysis of the role of nurse practitioners, physician assistants, and other nursing staff in HIV PrEP care found that nurse practitioners had greater odds of prescribing oral PrEP to patients (odds ratio = 1.40 and 95% confidence interval = 1.02–1.92) compared to physicians. According to the American Association of Nurse Practitioners, only 27 states and the District of Columbia grant full practice authority to nurse practitioners as of 2023; 12 states grant reduced practice authority and 11 states have restricted practice authorities for nurse practitioners.⁵⁴ Our results, coupled with previous literature,^50–53 support the need for practice- and policy-level changes that leverage nurse practitioners to accelerate and support the implementation of injectable PrEP for HIV prevention.

This study is not without limitations. First, we relied on a convenience sampling strategy to recruit providers from one geographic location in the United States; therefore, our findings may not be transferrable to clinical settings in other communities and geographical locations. Second, providers in our study had experience prescribing oral PrEP. The perspectives presented in this study may differ from clinicians who do not have experience prescribing oral PrEP. Third, we used semistructured interview guides to direct discussions about injectable PrEP implementation, which may present social desirability bias.

Finally, as the literature base for injectable PrEP expands, new scientific findings become known. Data highlighting greater incidence of hypertension and dyslipidemia among injectable PrEP participants,^22,55 the influence of body mass index on injectable PrEP pharmacokinetics,^55,56 and breakthrough infections associated with the development of integrase strand transfer inhibitor resistant mutations⁵⁵ were not explored in this study as potential factors influencing injectable PrEP implementation within clinical settings. Future research should explore how these concerns may impact injectable PrEP prescribing practices among health care providers.

The approval of injectable PrEP expands the array of prevention options for populations most vulnerable to HIV. Health care providers will play a pivotal role in ensuring effective and equitable implementation and uptake of injectable PrEP. Findings from this qualitative study make significant applied contributions to the sparse knowledge on health care provider perspectives regarding injectable PrEP and their considerations for clinical implementation post-FDA approval. Our results support the need for future research examining the various factors influencing injectable PrEP uptake at the patient, provider, and clinic levels to ensure meaningful clinical and public health impacts on HIV prevention and incidence.

Authors' Contributions

J.B.: Project administration, investigation, formal analysis, and writing—original draft. M.M.: Formal analysis and writing—review and editing. K.C.: Investigation and writing—review and editing. A.H.: Funding acquisition and writing—review and editing. G.D.M.: Funding acquisition and writing—review and editing. S.P.: Conceptualization, methodology, funding acquisition, resources, formal analysis, supervision, project administration, and writing—review and editing.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR001412 to the University of Buffalo. Jacob Bleasdale was supported, in part, by the National Institute on Alcohol Abuse and Alcoholism of the NIH under award number T32AA025877 to the University of Florida. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.