Next Generation Pre-Exposure Prophylaxis for Young Men Who Have Sex with Men: Lessons from System and Provider-level Barriers to Oral PrEP

Abstract

Next generation pre-exposure prophylaxis (PrEP) modalities that do not require daily regimens may address some of the barriers to daily oral PrEP among young men who have sex with men (YMSM). We conducted online semi-structured interviews with 30 YMSM to examine experiences and preferences related to HIV prevention care that may inform implementation of next generation PrEP. Barriers to PrEP care included initiating conversations about sexuality with providers; confidentiality concerns regarding disclosure of sexual practices and PrEP use to family; gaps in access to healthcare; and limited availability of affordable health services. Future implementation of next generation PrEP may benefit from providers addressing confidentiality concerns when discussing PrEP with YMSM; PrEP programs accounting for discontinuities in healthcare access among YMSM while strengthening access to affordable services; and collaborations between generalist providers and specialized clinics and providers to address providers’ education needs, which may increase as next generation PrEP becomes available.

INTRODUCTION

Young men who have sex with men ages 13–24 years (YMSM) are highly vulnerable to HIV acquisition. In 2019, 21% of the 36,801 new cases of HIV in the U.S. were observed among individuals in this age group, and 85% of these were among YMSM [1]. Adolescence and young adulthood are periods marked by exploration of sexual identity and risk-taking, which, coupled with lack of comprehensive sex education, may lead to behaviors associated with HIV transmission, including condomless anal sex [2–5]. Moreover, YMSM present suboptimal engagement in HIV prevention and treatment services, contributing to continued HIV transmission [4, 6].

Daily oral HIV pre-exposure prophylaxis (PrEP) is highly efficacious to prevent HIV transmission, including among YMSM [7–10]. However, PrEP uptake remains low among YMSM, with less than 30% of individuals under 24 years with clinical indications for PrEP estimated to be using the medication [11]. Barriers to PrEP use and persistence among MSM in general include concerns related to side effects, cost, medication adherence, and stigma related to PrEP use [12, 13]. In addition to challenges experienced by older MSM, YMSM face additional challenges navigating complex health systems, developing trusting patient-provider relationships, and accessing affordable and confidential HIV prevention services, which contribute to poor uptake and adherence to daily oral PrEP in this group [10, 12, 14–16].

Currently, PrEP is FDA approved for use as tenofovir-based, orally-delivered drug taken daily as a pill [10]. In addition to daily oral PrEP, however, other forms of PrEP that do not involve daily medications (i.e. next generation PrEP) are at different stages of the drug development pathway and may be available for clinical use in the U.S. in the near future. For example, oral tenofovir-based regimens taken at least two hours before and for two days after sexual encounters (i.e. event-driven oral PrEP) showed 86% efficacy in preventing HIV transmission in a placebo-controlled trial with MSM [17]. Based on these findings, event-driven oral PrEP has been recommended in international clinical guidelines as a PrEP option for MSM [18], although this modality has not received FDA approval in the U.S. Additionally, bimonthly injections of cabotegravir have been shown in a clinical trial to lead to a 66% reduction in HIV transmission compared to daily oral tenofovir due to increased medication adherence [19], and has recently been FDA-approved for adolescents and adults at increased risk of HIV transmission [20]. Other next generation modalities include long-acting oral medications [21], subdermal implants [22], rectal douches [23], and intravenous infusions of broadly neutralizing antibodies (bnAb) [24, 25], all of which are currently being evaluated in phase 1–3 clinical trials.

Behavioral research on investigational products that are currently being evaluated in clinical trials has the potential to optimize clinical trial conduct, and accelerate real-world implementation of PrEP modalities [26, 27]. If found to be effective, these next generation PrEP modalities may provide biobehavioral HIV prevention options that are more congruent with YMSM’s diverse needs, preferences, and lifestyles than modalities requiring daily administration, and thereby promote PrEP uptake and persistence. For example, YMSM experiencing sporadic or episodic HIV risk (e.g., transmission risk concentrated on weekends or vacation periods) may be particularly open to using event-driven PrEP modalities [28–30] and long-acting modalities may better fit the needs of YMSM who struggle with adherence to daily medications [31].

Preliminary studies have shown high acceptability of different next generation PrEP among several populations vulnerable to HIV infection, including YMSM [31–36]. However, next generation PrEP modalities may also introduce new challenges in accessing HIV prevention services. For example, YMSM may have concerns related to side effects of newly-approved products, especially when not familiar with the mode of delivery (e.g., have never received medication intravenously, rectally, or as subcutaneous implants) [37, 38]. Previous studies have also reported concerns regarding concealability of use of next generation PrEP modalities (e.g., subcutaneous implants that can be seen through the skin), which could potentially lead to unwanted disclosure of PrEP use and, indirectly, of sexual identity and practices to family and friends [39]. Moreover, the introduction of different PrEP modalities may also increase the complexity of patient-provider communications about HIV prevention options as these next generation PrEP modalities vary widely in modes of administration, interval between doses, and hypothesized side effects profiles. To date, however, there is a dearth of research examining how to plan for the implementation of next generation PrEP in our health systems. The present study examines YMSM’s experiences and interactions with healthcare providers and health systems for HIV prevention. Specifically, we examine how their experiences and insights may inform improvements to current and future PrEP services and delivery models.

METHODS

Participants and procedures

Between May and October 2020, we recruited 30 YMSM for online semi-structured individual interviews. Recruitment took place online through ads posted on social media platforms and websites (i.e., Facebook, Craigslist) that cater to youth in general and sexual minority youth and through targeted electronic mailing lists. Online recruitment activities targeted the metropolitan areas of Boston, MA, and Philadelphia, PA. Participants were eligible to participate if they were 15–24 years old, were assigned male sex at birth and identified as male (i.e. cisgender man), self-reported being HIV negative or HIV status unknown, had at least one episode of condomless anal sex with another man or transgender woman in the past six months, and were fluent in English. We used purposive sampling to ensure diversity with respect to race/ethnicity and previous PrEP use. The sample size for this study was determined based on previous qualitative HIV studies with YMSM by our research team [31, 40] as well as indications of data saturation in the data collection process.

Interested individuals took a brief online screener survey to determine eligibility. Research staff contacted eligible individuals on the phone to confirm eligibility and explain study procedures. Participants then met with a member of the research staff on SecureVideo, a HIPAA-compliant video software, for a brief self-administered survey immediately followed by an online semi-structured interview planned to last 60 minutes (duration range: ~30–120 minutes). Participants received a gift card worth $50 for participation. All participants provided written informed consent/assent electronically. We obtained a waiver of parental consent for individuals under 18 years old. The Institutional Review Board at University of North Carolina reviewed and approved all study procedures and materials.

Instruments

The brief online survey assessed participants’ demographic characteristics (e.g., age, race, ethnicity, education, income, relationship status), sexual behaviors (e.g., number of partners and number of condomless sex acts with men and transgender women in the past six months), and access to health services (e.g., insurance status, previous HIV/STI testing, and PrEP awareness, interest, and use).

The semi-structured interview guide was created based on our previous work on engagement in PrEP care among sexual minorities and refined based on content analysis of social media posts related to sexual health and PrEP by U.S. youth to update terminology and enhance cultural appropriateness of language and questions for age group [41]. The semi-structured guide contained a series of questions assessing topics related to healthcare and HIV prevention, each followed by probes to provide greater depth in participants’ responses. Main domains included perceptions and previous experiences in general healthcare (e.g., previous interactions with healthcare providers and access to preventative services) and HIV prevention services (i.e., HIV/STI testing and daily oral PrEP), as well as preferences and acceptability across biobehavioral PrEP products. Sample probes relevant to the present study are shown in Table 1.

TABLE 1 –

Sample probes from semi-structured interview guide

Probes
• Do you have a primary care provider?
• Can you tell me about when you started going to this provider? How old were you? Is this the same provider who used to see as a child?
• What type of provider (e.g. NP, PA, MD, pediatrician, adolescent medicine, etc.) do you see regularly?
• What kind of health issues do you discuss with your primary care provider?
• What about sexual health issues? Why not?
• What would make you more comfortable talking about sexual health with your provider?
• What is the role of your family in your relationship with your provider, if any?
• How do you determine which PrEP modality would be best for you?
• Where would you go to look for more information about next generation PrEP (healthcare providers, friends, family)?
• What would be the role of your family, if any, in your decision about what kind of PrEP you would choose?
• How would you bring up conversations about PrEP with your provider? How do you think this conversation would go?
• What would be challenging about having conversations about PrEP with your provider?

Boldface = probes added after initial interviews

In addition to asking about daily oral PrEP, we presented five hypothetical next generation products in semi-structured interviews: PrEP delivered as event-driven oral pills before and after sexual intercourse; bimonthly intramuscular injections; bimonthly intravenous bnAb; yearly subcutaneous implants; and rectal douches administered before intercourse. Interviewers provided a brief description of each PrEP modality before asking questions about preferences and acceptability related to HIV prevention options. Semi-structured interviews also included a cognitive interview component, in which participants were asked to read, interpret, and provide suggestions for improvement of written descriptions of PrEP products (daily oral and next generation) for use in future research [42].

Data analysis

Semi-structured interviews were audio-recorded and professionally transcribed. Interview transcripts were made available to the research team early during data collection and preliminary data analysis informed further semi-structured interviews, which facilitated monitoring the data for thematic saturation. After completion of data collection and immersion in the data, we used inductive and deductive approaches to develop an initial codebook draft based on a subset of transcripts; specifically, codes were defined a priori based on the research questions and emerging topics from interviews. The codebook was iteratively refined after coding additional interview transcripts [43]. When the codebook was final (i.e., existing codes were able to capture and categorize all relevant data), we proceeded to code all interview transcripts. Each transcript was coded by at least two coders, who systematically compared and discussed code applications and reconciled coding divergences (i.e. negotiated agreement coding) [44]. This approach ensures that at least two coders agreed upon all code applications, enhancing the dependability of the coding process.

Using a phenomenological approach [45], the first author reviewed relevant coded excerpts for semantic (i.e., explicit) and latent (i.e., interpretative) themes related to YMSM’s lived experiences and understandings regarding accessing or forgoing medical care and PrEP services that could inform future implementation of PrEP services [46]. After identifying themes, we reorganized the data in a matrix where participants were listed in rows and columns contained themes (i.e. the framework method) [47]. This was done to prevent over-fragmentation of data that may happen when transcripts are reorganized into coded excerpts, which may obfuscate the context and meaning from individuals’ narratives [48, 49]. After having identified preliminary themes, we convened a meeting with the youth advisory board (YAB) of YMSM at the University of Pennsylvania to discuss research findings and gather youth’s input. We then refined our description of the findings and lessons for implementation based on feedback from the YAB.

RESULTS

Participants’ age ranged from 16–24 years (median=22, IQR=3.5) and three individuals (10%) were under 18 years old. About half identified as non-Latinx White (n=14, 47%) and most participants identified as gay (n=22, 73%). Almost all participants had health insurance (n=29, 97%) and most had a primary care provider (PCP) (n=24, 83%). Twenty-eight participants had heard of PrEP prior to the study (93%) and about half (n=14, 47%) had previously been prescribed PrEP for HIV prevention. Table 2 shows sociodemographic characteristics of our sample.

TABLE 2 –

Sociodemographic characteristics of participants in semi-structured interviews (N=30).

	Mean (SD)
Age (range: 16–24) / Median=22 (IQR=3.5)	21.4 (2.39)
	N (%)
Age group
15–17	3 (10%)
18–20	6 (20%)
21–24	21 (70%)
Race/Ethnicity
Non-Latinx white	14 (47%)
Non-Latinx Asian	7 (23%)
Latinx	4 (13%)
Non-Latinx Black	2 (7%)
Multiracial/Other	3 (10%)
Sexual orientation
Gay/homosexual	22 (73%)
Bisexual	8 (27%)
Currently in school	18 (62%)
Highest level of education completed
Less than high school	3 (10%)
Graduated high school/GED	4 (13%)
Some college/tech or vocational school	10 (33%)
Four-year college graduate or more	12 (43%)
Currently has health insurance	29 (97%)
Currently has primary care provider	24 (83%)
HIV test
Past year	26 (87%)
Ever	26 (87%)
STI test (ever)	27 (90%)
Heard of oral PrEP prior to study	28 (93%)
Oral PrEP use
Ever	14 (47%)
Current	13 (43%)
Interested in taking PrEP in the future (if not currently on PrEP)
Extremely likely	2 (12%)
Likely	4 (24%)
Undecided	10 (59%)
Unlikely	1 (6%)

We identified four main themes related to provider- and health system-level factors that may influence acceptability of PrEP products and inform implementation of health services for YMSM: 1) initiating and maintaining communication about sexual health needs and PrEP with healthcare providers, 2) involvement of family in care and concerns about confidentiality, 3) changes and discontinuities in access to care, and 4) availability of affordable services. YAB members also believed that these four themes were relevant and salient for YMSM accessing PrEP services.

Conversations about sexual health and PrEP

Several participants reported discomfort discussing their sexuality with providers, sometimes stemming from expectations of prejudice and discrimination against non-heteronormative sexual practices. This was particularly salient for younger participants in the sample, who were often less comfortable discussing their sexual practices and identities with providers:

[Sexual health] is not really, uh, a topic we really discuss. So, then I just err on the side of not telling him [the provider]. Because I’m not at that stage where I feel comfortable discussing it [sexual practices] with him since he doesn’t really make it a habit to discuss it. Nor, do I feel like he would be open to listening to it. So, that’s why I never really talk about it.

(16 years, Asian, PrEP-naïve, PHL-15)

Some participants, regardless of their age, perceived providers to lack skills in having conversations about sexual health with sexual minority patients, limiting opportunities to communicate about the topic:

One time [my provider] said, “Do you have a girlfriend?”, and I said no. And then she paused, awkwardly, for like ten seconds and she was like, “A boyfriend?” And I was like, “No”. And then she was, like, “Okay.” And that was the end of the conversation. So, we like didn’t really broach it. We’ve never gone further than that.

(24 years, Asian, PrEP-experienced – PHL-11)

A few YMSM of color reported that building trusting relationships and communicating about sexual health with white providers was particularly challenging due to instances of experienced or perceived racism and ethnicity-based discrimination in previous interactions with these providers. In some cases, participants preferred non-white, sexual minority providers, who were perceived to better positioned to relate to their lived experiences and health needs:

When you go to the doctor, you wanna talk to someone who is knowledgeable on what’s going on with you, but someone who also understands you, you know, mentally. You want them to understand you emotionally. And so, having someone who is gay and a minority, you know, a minority racially, allows me to relate to him. You know, I’m gay, I’m Middle-Eastern, there’s a lot of shit that I don’t know about in the world of medicine but he’s there to help me through it.

(23 years, Middle-Eastern, PrEP-experienced, PHL-12)

Even in instances where participants developed rapport with providers and had regular conversations about HIV/STI testing and sexual behaviors that may constitute PrEP indications, PrEP was sometimes not addressed in sexual health conversations:

We had a good relationship. It was very open. I felt like I could talk about whatever with her and feel very comfortable, (…) I also got the STD testing through her. (…) [But] I haven’t [talked about PrEP with her], which I think is interesting. I feel like so many people are on it that I feel like it would’ve been mentioned to me by a provider at this point, but it hasn’t.

(24 years, white, PrEP-naïve – RI-12)

Perceiving providers to have low knowledge about daily oral PrEP compounded participants’ uncertainties related to discussing sexuality with providers, a perception shared among YAB members. Many participants reported having previous negative experiences in which providers were not aware of PrEP and/or expressed skepticism toward PrEP for HIV prevention. These communication challenges and perceived knowledge deficits among providers motivated participants to change providers or go to clinics specializing in LGBTQ-inclusive care for HIV prevention and PrEP.

I asked [my previous provider] to get onto PrEP because I was single and I was, you know, having a time and having sex with multiple partners. But my primary care provider, I was his first ever open LGBT patient. And when reviewing PrEP, (…) he’s like, “The side effects aren’t worth the benefit,” so he wouldn’t prescribe it to me. It’s because of that I switched healthcare providers because he is really out of touch with the needs that I have as a gay man. (…) You’re rejecting something basic, (…) clearly, you’re not meeting my needs as a healthcare provider so, like, bye. (…) Now I actually commute all the way up to [a LGBTQ-friendly clinic in a neighboring city] for healthcare, because they’re understanding. They understand the problems I’m having, [and my previous provider] was very uncomfortable discussing my sex habits with men.

(24 years, white, PrEP-naïve, RI-14)

Difficulties communicating about sexuality and HIV prevention needs and low perceived knowledge was also a potential barrier to rollout of next generation PrEP. When discussing next generation products, most participants highlighted the role of healthcare providers helping patients make informed decisions regarding PrEP options. This was particularly relevant if participants were less familiar with medications with similar routes of administration or if the modality involved medical procedures perceived to be more complex (e.g., inserting implants, placing intravenous catheter for infusion of bnAb):

I feel like [my preferences for next generation products] would change depending on my degree of trust in the provider. Especially if I don’t know about the method. (…) The less I know, the more insecure I feel about it, so the more I would need to trust the provider to make a decision. (…) [For example] having to go through a procedure to put an implant in my arm, maybe if I don’t trust the provider that much, I wouldn’t be willing to [do it]. Maybe I can take the injection, or even on-demand PrEP.

(22 years, Multiracial, PrEP-naïve, RI-15)

Some participants who did not have open, trusting relationships with their regular providers would prefer to access next generation PrEP through other health services (e.g., specialized clinics), while seeing their regular PCP for other general health needs:

[I would like to know more] information about the medication [next generation modalities]: what kind of injection, if it’s intramuscular, if it’s intradermal, intravenous; if it would be administered by like anyone, any healthcare physician, any type of clinic, or if it would have to be specifically prescribed by a PCP. (…) I feel some people would not prefer to have their PCP know everything about their medical history or their personal lives. So I feel that would impact [my acceptability of the products] as well if it could be administered by any clinic or just having that confidentiality [from the PCP]. That would boost wider adoption.

(23 years, Asian, PrEP-naïve, PHL-09)

Family involvement in care and concerns about confidentiality

While our semi-structured guide did not initially include questions and probes about the role of family members in participants’ general and sexual health-related care, this topic emerged in early interviews and was further explored in subsequent data collection. Many participants, reported high levels of involvement of their family in their general healthcare and sometimes even had the same provider as their parents, leading to concerns about providers breaching confidentiality related to sexual health topics.

I didn’t really want to tell my parents I was trying to get on PrEP to have sex [in] a non-committed relationship. (…) I was afraid [the provider] would spill the beans (…). Because, you know, I come from a first-generation household of, like, very strong Catholic parents. They know I’m gay but I don’t talk to them about my sex life.

(24 years, white, PrEP-naïve, RI-14)

Being included in their family’s health insurance was also described as a barrier to daily oral PrEP use due to fears of unintended disclosure of PrEP indications or use to the insurance policyholder (e.g., via an explanation of benefit [EOB] form). In some instances, participants preferred to not access HIV/STI testing and PrEP services through their regular medical provider or insurance plan, and instead sought free PrEP provision in other places, such as at community clinics with cost assistance programs:

It’s my parents’ insurance. I mean, I feel like they wouldn’t care so much, but it would just be awkward, ‘cause they’d see it on their insurance, obviously. And then the issue is, if I’m using their insurance, there’s still a cost, and if I decide not to put it under their insurance, there’s an expensive cost. I wouldn’t want to pay full price for a medication, probably. Even though I know there are places out there that can help with that, there’s Planned Parenthood, and everything, there’s multiple places you can go to, to get around that.

(19 years, white, PrEP-naïve, PHL-06)

Participants had mixed opinions as to how their family’s involvement in their healthcare could affect decisions regarding next generation PrEP modalities. A few participants who were out to their families and open about their PrEP use saw family members as potential sources of information and support for choosing from HIV prevention options.

My mom is the only person who knows about my health conditions. (…) She knows about my allergies. She knows I take PrEP. She knows that I get tested regularly. She knows about every STD that I’ve had, about every sort of hospital visit I’ve had. So, she’s 100% in which is nice to have that support system, you know? It’s someone who’s not judging you, which is nice.

(23 years, Middle-Eastern, PrEP-experienced, PHL-12)

Most participants, however, did not feel comfortable discussing sex and PrEP with family members and would prefer PrEP modalities that would be easier to conceal from parents. For example, participants were worried about self-administered medications (e.g., oral pills, PrEP douche) because they would require storing medication containers at home:

I guess having to take a medication every day, I would be maybe worried if they [my parents] questioned me about it. I guess getting injections and implants would be more discreet to [do].

(23 years, Multiracial, PrEP-naïve, RI-15)

A few participants also reported being concerned about parents finding out about long-acting PrEP modalities, such as PrEP implants that are visible or palpable through the skin, and PrEP injections, which could raise questions from parents.

If [the PrEP injection] does leave a bump, or, you know, a sore mark, like, a flu shot sore, if it does leave that then if your parents find out they might be a little bit suspicious. (…) Because then, you know, they’ll think at first you’re injecting some drug or whatever. They [would be], like, “You already got your flu shot, what are you taking?”

(19 years, Latinx, PrEP-naïve, PHL-14)

Discontinuities in care

Life circumstances that often take place in late adolescence and young adulthood, such as starting college, moving cities, and changing jobs, were often accompanied by changes and discontinuities in access to healthcare. Some participants discussed discontinuities in access to a regular provider when “aging out” of pediatric care or after moving out of their hometown. In some situations, relatively simple medical care such as STI testing and treatment involved navigating several different appointments at different health centers, indicating fragmentation in the care received:

I recently transitioned from my pediatrician that I have had since I was a kid to [an] adult care doctor, a regular doctor. But during that transition, I was already referred to a sexual health clinic at my school when I decided to get tested (…). When I went to my school’s health center, they tested me and then I contracted gonorrhea. They referred me to other places to get some care [for gonorrhea]. And then one time I contracted gonorrhea again within the couple months afterwards. And since the healthcare at my school was not available and to make an appointment with my pediatrician took some time, what my university recommended for students to get care outside hours of the regular healthcare or student center, was to go to [a hospital]. There, they recommended me to a doctor in the infectious disease center of the hospital.

(19 years, Asian, PrEP-experienced, RI-04)

The participant above continued to explain that some of the discontinuities in care experienced accompanied increases in sexual activity and HIV risk, making access to comprehensive care all the more important:

I went to the infectious disease center and I started PrEP with them. I didn’t talk to my pediatrician or PCP [adult care] at the time, because I was not meeting with my pediatrician since transitioning from high school to college, and also transitioning to my current PCP. (…) I would think I’m comfortable with talking [about PrEP] with either my pediatrician or my PCP at the time, but this was like a year after I turned 18, or starting college, so the numbers of sexual partners I’ve had increased a bit more.

(19 years, Asian, PrEP-experienced, RI-04)

Participants also described frequent changes in insurance coverage during this period of their lives, including moving in and out of their parents’ insurance plan as they got on student insurance plans through college or started new jobs. A few participants discussed how those changes in insurance coverage have impacted their decision to initiate oral PrEP:

The insurance I have at [college] is different from the insurance I have at home. And I don’t know, because [the former] expires at the end of the school year. So I don’t know, if during the summer I would have the same access to [PrEP], ‘cause I’m not sure [if] my insurance at home covers it. I know at [college] it covers it, but I’m not sure if they both do and I don’t know how it works, like, transferring between insurance.

(20 years, Multiracial, PrEP-naïve, PHL-07)

For participants who experienced gaps in their access to a regular medical provider or health insurance after going to college, universities’ student health services were described as a key resource for general health and HIV prevention needs:

Because I don’t have a primary care provider here, I have no idea where I would go [to get PrEP] or what I’d do or who I’d call. But because there’s the university health service, it’d be very easy to just say, “I’m interested in this.” And I know they’d connect me to the right resources.

(19 years, white, PrEP-naïve, RI-08)

Some participants also expressed concerns that gaps and discontinuities in access to care would impact their access to next generation PrEP options.

Insurance coverage of these various methods would be something that would change at different points in my life because I’m recently out of school and recently on new insurance and I know as my career unfolds my insurance is going to change. So I think coverage of the various methods would be something that would change over time.

(23 years, white, PrEP-naïve, PHL-04)

Therefore, uncertainties related to whether and where participants would have access to care in the future was described by a few participants as a barrier to uptake of long-acting modalities, such as yearly PrEP implants:

I guess stability of where I’m living would be kind of important [in making decisions regarding next generation modalities]. So I probably wouldn’t get the implant if I didn’t know if I’d be able to get it removed in a year. Because it seems like with all the other treatments [modalities], if you have a side effect or if you don’t like it you just don’t take it. You just stop. But with an implant you can’t really stop without a medical professional. So that’s the one I’d be most scared of if I didn’t know if I had access to healthcare in the future.

(23 years, Asian, PrEP-experienced, RI-05)

Conversely, a few participants perceived long-acting modalities, especially PrEP implants, to be easier to follow-up with if facing interruptions in insurance coverage because these products would require less frequent visits to healthcare:

I definitely think that for me, the implant would be the best with my sort of, like, lifestyle right now and for where I am professionally. Especially because where I am in terms of the job market and my education right now, I can definitely see myself moving long distances. And any time you move, you need to get new healthcare providers. So something long term like that where I wouldn’t need to worry about an HIV prevention method for many, many months because it’s in my body already would be really beneficial.

(24 years, white, PrEP-naïve, RI-11)

Affordability, availability, and access to health services

Almost all participants considered cost to be an important aspect of decisions regarding HIV prevention options. Many participants who were being prescribed oral PrEP reported relying on free or low-cost PrEP programs through community clinics or cost assistance programs:

It was very easy to initiate the conversation [about PrEP] with my provider. Getting it was another matter. I had the prescription filled and it was originally gonna cost a few thousand [dollars], and then it dropped down to $300 with my insurance, but that was still too expensive for me. I don’t know how it happened, but there was some program I think that when combined with my insurance brings the cost down to zero. So thankfully they were able to figure that out for me at the pharmacy. But that was difficult, to get it.

(21 years, white, PrEP-experienced, RI-07)

Many participants were uncertain as to whether next generation PrEP would also be made affordable through similar programs.

I think the biggest issue [about next generation PrEP] would be if it is an expensive product and it’s not covered by insurance. (…) Right now, my medical insurance covers [daily oral PrEP], but I still see what it costs to them, and it’s expensive. So if I would have to pay that out-of-pocket, I would’ve not done it.

(22 years, white, PrEP-experienced, PHL-01)

This concern was particularly salient for modalities perceived to be less likely to be covered by insurance (e.g., event-driven oral PrEP, PrEP douches), more expensive (e.g., bnAb), or that would require specialized medical procedures for administration/insertion (e.g., PrEP implants).

Cost is something to consider, more so for the implant. Because I can’t imagine the injection costing much. But for the implant, you know, [it’s] like a surgical procedure.

(21 years, Black, PrEP-experienced, PHL-05)

In addition to cost and concerns about insurance coverage, many participants were also concerned about availability of services that would provide next generation modalities. Modalities that would require more frequent visits to health services, such as bimonthly intramuscular injections or bnAb infusions, were perceived to be less accessible for participants facing challenges in accessing regular healthcare.

I know some people who either don’t have cars or don’t have means of getting to the doctor’s office as easily as I do. Like, I have my own car, so I would be able to very easily go to the doctor’s office to get an injection or to get an implant or something like that. But for other people who don’t have such stable transportation, they might have to rely on a parent or something like that to get to the doctor’s office. And then it becomes more of a process and some parents aren’t as okay with medications like this, and then, they’re not able to get that kind of medication at all.

(17 years, white, PrEP-naïve, RI-03)

Many participants highlighted the importance of wide availability of health services that could administer next generation PrEP products, both in terms of geographical availability and type of provider or clinic that would be qualified to provide these services:

[I would consider] how widely available [next generation PrEP] it is, not just like in specific areas of the country. (…) Especially if I’m traveling or out of where I normally am, because where I normally stay, I feel like I am like pretty sure that I can like have access to medication or treatment whenever I need to. However, if it’s like out of network or if I’m like traveling, (…) having in mind [that] just about anyone can do it gives you that reassurance that you can still have access to it even if you’re going anywhere out of where you normally are.

(23 years, Asian, PrEP-naïve, PHL-09)

In commenting the above quote, YAB members suggested utilizing online tools to help connect youth to HIV prevention and PrEP services, such as web-based apps to facilitate scheduling of medical visits and filling prescriptions, and telehealth visits without the need to travel to health clinics.

DISCUSSION

While next generation PrEP modalities show promising results in clinical trials [19, 22–25], real-world implementation of these technologies may lag if preferences and acceptability among YMSM are not taken into consideration in the design of PrEP delivery programs. Our study explored YMSM’s perceptions and experiences related to currently available and next generation PrEP, and identified key considerations for future implementation of these products.

We identified lack of knowledge about PrEP among providers as a barrier to conversations about HIV prevention and daily oral PrEP uptake. This finding is consistent with the existing literature on oral PrEP [16, 50–53]. Ongoing implementation of daily oral PrEP has relied on specialists (e.g., HIV and infectious disease clinicians, providers at health centers specialized in LGBTQ-inclusive care), which have acted as “innovators” and “early adopters” of PrEP [54, 55]. As new PrEP modalities become available, clinical guidance on HIV prevention options with become more complex and require greater training and education for providers. Given primary care providers generally under-prescribe daily oral PrEP currently, specialized clinics and providers will likely be key in helping structure future PrEP delivery programs that account for the diversity in PrEP modalities, as well as developing education initiatives on next generation PrEP for a wider audience of providers.

However, wide dissemination and implementation of varied PrEP modalities will also require involving generalist providers working at non-specialized clinics. To that, engaging PrEP champions, who would lead multidisciplinary teams within non-specialized clinical practices to facilitate prescribing by providers and work with staff to streamline administrative procedures related to PrEP provision may be promising [56]. Generalist providers will also likely still have a role in identifying and, if necessary, referring PrEP-indicated individuals to specialized centers, especially patients who are less motivated, with low HIV risk perception, and those without adequate access to healthcare who may be unable to access specialized PrEP services directly. Open communication about sexual practices and HIV prevention with generalist providers may therefore be extremely valuable and may help patients make informed decisions about HIV prevention modalities that are congruent with their needs, lifestyles, and expectations.

To date, however, lack of cultural competence to provide care for YMSM among providers, including biases and overt discrimination related to sexual identity and behavior, has negatively impacted PrEP uptake [50, 51, 53, 57, 58]. YMSM of color, who may experience racism in addition to heterosexism/homophobia in healthcare, face even greater challenges to communicating about HIV prevention and PrEP with providers [53, 59]. Recent systematic reviews indicate that interventions targeting educational curricula and other training programs can be effective in reducing anti-YMSM bias and increasing comfort in providing care for YMSM patients among healthcare providers and students [60, 61], and provider education interventions have been shown to increase daily oral PrEP prescription behaviors among providers [62, 63]. Future research should also evaluate provider-focused training and education initiatives in facilitating access to next generation PrEP modalities approved for clinical use among youth (e.g., injectable cabotegravir). Importantly, to effectively address patent racial and ethnic disparities in PrEP access [64], such training programs should also incorporate components to address racial biases and discrimination among providers involved in PrEP provision services.

Our results also suggest that providers engaging in communication about HIV prevention with sexual minority youth would do well to consider the social and family contexts of their patients. Previous studies have indicated that fear of unintended disclosure of sexual identity or behaviors to parents are an important deterrent of interest in and use of daily oral PrEP among youth in the U.S. [10, 65, 66]. Our study shows that similar concerns may also influence decisions about next generation modalities. For example, YMSM may avoid next generation PrEP modalities that involve taking medication at home or that may be visible to family members. Other studies have shown that individuals may also experience PrEP-related stigma from sexual partners and other individuals in their social networks [12, 67, 68], which may persist with the advent of next generation modalities. At the same time, some participants in our study also had supportive family relationships that would be potential resources in helping participants make health-related decisions and providing adherence support. Therefore, providers should assess YMSM’s social relationships, especially with family members, to evaluate their support networks and assist patients’ in making individualized considerations regarding concealability of PrEP products in conversations about HIV prevention options.

Confidentiality in PrEP care among youth also encompasses disclosure of sexual practices by providers and issues related to insurance. In several states, there are laws that ensure that youth can initiate daily oral PrEP without parental consent and legislation to allow individuals to forward EOB forms to an alternative electronic or physical mail address instead of that of the primary insurance policyholder’s [10, 14, 69]. However, as we have shown, concerns persist about disclosure of access to HIV prevention care and PrEP to family members and insurance policyholders, usually parents. Unwanted disclosure of access to PrEP use is concerning because it can “out” sexual and gender minority youth to family and others [39]. Some YMSM in our study bypassed these concerns by accessing daily oral PrEP through drug assistance programs or community clinics such that they would not rely on their family insurance plan. However, out-of-pocket costs of PrEP to the end-user still vary greatly according to type of insurance coverage, if any, and access to state, local, and private-funded cost assistance programs, which may be challenging to access and navigate [70]. Accessing affordable PrEP may be particularly difficult for YMSM, who often experience changes in type of insurance coverage and gaps in coverage during adolescence and young adulthood, which have been linked to poor healthcare utilization and unmet health needs [71]. YMSM who are inexperienced in navigating the fragmented U.S. health system are particularly susceptible to such barriers to PrEP use and persistence [12]. These insurance and health system complexities may be exacerbated with the advent of next generation products, and PrEP implementation should consider affordability of these products to avoid worsening disparities in PrEP access and promote equity. Health clinics providing next generation modalities may benefit from individualized patient navigation and case management services to assist YMSM in evaluating appropriate and affordable forms of accessing PrEP products in a confidential manner. These services should also assess and plan for potential discontinuities in healthcare access that youth may experience.

Another important element of decisions about next generation PrEP is the distribution of health services to provide these products. Almost a decade after initial approval of daily oral PrEP for HIV prevention in the U.S., geographical availability of PrEP clinics is still limited [72]. Health services focusing on the needs of MSM and other LGBTQ individuals, which have spearheaded the roll-out of oral PrEP in the U.S., are also concentrated in large urban centers [73]. Next generation PrEP modalities that need specialized procedures for insertion (e.g., implants) or facilities for administration (e.g., bnAb infusion) may come with additional distribution and logistical challenges and further strain existing PrEP services. For YMSM who are in or will pursue higher education, engaging college health centers may be key in improving continued access to next generation PrEP. These centers are well-positioned to meet students’ needs without the need for intermediation of family members in a moment in which many YMSM may experience heightened HIV risk [74], leading to a recent national guidelines recommending daily oral PrEP as a standard healthcare service in these institutions [75].

In addition to MSM and LGBTQ-inclusive clinics and university health services, which may also be challenging to access for youth still on their parents’ insurance, continued access to next generation PrEP products will necessitate a wide distribution network in varied geographical locations to account for youth in different insurance statuses and life circumstances (e.g., relocating across cities, starting and ending college, in between jobs, etc.). Telemedicine-based models and other technologies to make in-person medical visits non-mandatory for PrEP initiation, PrEP delivery within pharmacies or retail care clinics, and making PrEP available over-the-counter have been proposed for daily oral PrEP [76, 77] and may also facilitate future implementation of next generation PrEP. In some of these delivery models, in addition to making PrEP available at alternative locations (e.g., pharmacies, retail care clinics), patients may self-collect specimens for regular laboratory follow-up and receive prescriptions at home, facilitating both PrEP initiation and retention in care [77]. However, many of these PrEP implementation interventions have yet to be rigorously evaluated. Future research should evaluate the role of different PrEP provision models and strategies in streamlining initiation of different PrEP modalities, addressing disparities in access and retention in care, and reducing HIV transmission among youth.

Our study is not without limitations. None of the next generation PrEP modalities discussed in the present study had been approved for clinical use in the U.S. at the time of conducting semi-structured interviews; as such, participants’ attitudes and beliefs toward these products were based on hypothetical scenarios and characteristics of the products. Product characteristics may change as part of the drug development pathway, which in turn may influence participants’ preferences. Still, research on behavioral determinants of interest and acceptability of biomedical products is crucial for optimal drug development and future implementation [26]. We encourage further research to continue to examine acceptability of and preferences for investigational biobehavioral HIV prevention products in all phases of the drug development process, including with previous participants in clinical trials and individuals in priority populations in the HIV epidemic (e.g., YMSM). Second, our recruitment efforts targeted YMSM 15–24 years old living in urban centers in the Northeast U.S. and our findings may not be generalizable to other YMSM, particularly those under 15 years of age and/or living in non-urban areas. Our purposive sampling ensured diversity with respect to race/ethnicity and daily oral PrEP experience in two priority jurisdictions in the HIV epidemic and gave us breadth in participants’ perspectives, which we believe may provide implementation lessons that are translatable to other settings and populations. Future studies should continue to examine participants’ beliefs and experiences with daily oral and next generation PrEP products to better design and implement HIV prevention services for different settings in the U.S. and globally.

These limitations notwithstanding, our study contributes to the understanding of preferences regarding HIV prevention and health systems-, clinic-, and providers-level factors that may influence uptake and retention in PrEP services. Early engagement of behavioral and social sciences research to examine acceptability and preferences of experimental PrEP products can improve conduct of ongoing clinical trials, and accelerate drug development and implementation of technologies shown to be effective [26, 27]. Next generation PrEP holds promise to address disparities in HIV transmission [78], but realizing this potential will require addressing disparities in healthcare access currently in place and those that may emerge as next generation PrEP is implemented. Engaging and training healthcare providers, establishing a wide network of free and low-cost PrEP provision services that operate regardless of insurance status, and understanding when and how to involve family members and other individuals in the social networks of YMSM will be key to that end.