RECOMMENDATIONS FOR INTERVENTION CONTENT TO ENHANCE HIV PRE-EXPOSURE PROPHYLAXIS UPTAKE AMONG MEN WHO HAVE SEX WITH MEN RECEIVING CARE AT SEXUALLY TRANSMITTED DISEASE CLINICS

Background and objective Pre-exposure prophylaxis (PrEP) uptake has been suboptimal. Sexually transmitted disease (STD) clinics provide important opportunities to scale PrEP uptake. Material and methods To inform the development of a brief intervention to enhance PrEP uptake in STD clinics, we conducted 32 qualitative interviews to explore barriers and facilitators of PrEP uptake among PrEP eligible, PrEP naïve, and men who have sex with men (MSM) presenting for STD screening services. We also solicited input for intervention components to enhance PrEP uptake at STD clinics. Results Most participants’ self-perceived HIV risks were low despite reporting unprotected anal intercourse. Many were reluctant to take any medications, expressed apprehension about perceived side effects of PrEP, and were unaware of how to obtain PrEP. Participants recommended that interventions focusing on enhancing PrEP uptake in STD clinics should include: culturally tailored educational materials about PrEP, informational graphics indicating PrEP’s relative efficacy in reducing HIV transmission risks, and comprehensive PrEP navigation. Most participants did not feel strongly about gender, race or ethnicity of providers; however, nearly all preferred gay-affirming providers. Brief interventions to enhance PrEP uptake among MSM in STD clinics Recommendations for Intervention Content to Enhance HIV PrEP Uptake Among Men e48 J Mens Health Vol 16(3):e47–e59; 03 September 2020 This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License. ©2020 Amy S. Nunn et al. should include efforts to raise self-awareness of HIV risk, provide information about PrEP’s efficacy relative to other interventions, underscore PrEP’s relatively few side effects, and provide culturally tailored messaging.


INTRODUCTION
An estimated 37,600 new HIV infections occur annually in the United States (US); 70% of infections are among gay, bisexual, and other men who have sex with men (MSM). 1 Pre-exposure prophylaxis (PrEP) is a biomedical HIV prevention intervention that can significantly reduce HIV acquisition among MSM. PrEP is a once-daily, oral antiretroviral medication (co-formulated tenofovir disoproxil fumarate and emtricitabine, TDF/FTC) approved by the US Food and Drug Administration to reduce HIV transmission among HIV-negative individuals at risk for HIV infection. 2 PrEP has been proven highly effective in reducing HIV acquisition among MSM in clinical trials. 3,4 However, PrEP uptake among populations most at risk of HIV infection, including MSM of color, remains a challenge.
Pre-exposure prophylaxis programs have expanded across the US since PrEP was approved in 2012. [4][5][6] While over 70,000 people initiated PrEP by 2017, 7 they represent only a small fraction of the 1.23 million individuals, the Centers for Disease Control and Prevention (CDC) estimates, clinically indicated for PrEP. 8 PrEP awareness, uptake, and adherence are lower among younger and Black/African American and Hispanic/Latino MSM than among White MSM. 6 The highest rates of HIV infection in 2016 occurred among Black/African Americans and Hispanic/Latinos (42 and 27%, respectively). 9 However, only 10% of people starting PrEP between 2012 and 2016 were Black/African American, and only 13% were Hispanic/Latino, compared to 73% who were White. Low self-perceived risk is a common barrier to PrEP uptake and other prevention interventions. [10][11][12][13] Other reported reasons include concerns about side effects, 14 stigma, 15 the prohibitively high cost of PrEP, 16 and accessibility of PrEP services. 17,18 Other studies have examined the barriers and facilitators to PrEP uptake, [15][16][17] but little is known about how to enhance PrEP uptake, particularly among MSM of color and in sexually transmitted disease (STD) clinics or safety net settings most likely to serve individuals at highest risk for HIV acquisition. Little is also understood about the requisite "wrap-around" services that would enhance PrEP uptake. In this study, we explored barriers to PrEP uptake among a diverse population of HIVnegative MSM at high risk for HIV acquisition. We also solicited their opinions and recommendations about how to design effective, brief interventions to be delivered in busy STD clinic settings that can enhance PrEP uptake.

Patient sample and clinical setting
Participants were approached for participation if they were identified as male, had never used PrEP, and met current CDC recommendations for PrEP use. 18 We used purposive sampling to recruit participants from an urban STD clinic that serves a diverse patient population in Providence, RI. The clinic offers STD screening services, HIV care, and PrEP services. The inclusion criteria for the study were: identifying as a man who has had sex with another man in the last 6 months, being HIVnegative, and not currently taking PrEP. Participants also met CDC recommendations for PrEP, which include having any male sex partners in the last 6 months, not being in a monogamous relationship with an HIV-negative partner, reporting any condomless anal sex in the past 6 months, or reporting perspectives on how best to present information about HIV risk and PrEP. Participants were also asked about their preferences for the race, ethnicity, and sexual orientation of health care providers or interventionists delivering any potential PrEP uptake intervention.

Data analysis
We used the grounded theory approach in this study. We interviewed participants until we reached saturation, when no new data were emerging. 21-23 An inductive approach using a coding scheme to identify themes and categories guided data analysis. Three study team members first analyzed the interview transcripts to identify recurrent themes, then developed a preliminary coding scheme. They independently developed and applied a final coding scheme, using NVivo 11 Software 24 to ensure consistency. Discrepancies were discussed and resolved among the research team.

RESULTS
A total of 32 participants were enrolled, from 20 to 49 years of age, with a median age of 27 years. Twenty-eight participants (88%) had either private health insurance (through an employer or purchased themselves) or state-funded insurance (i.e., Medicaid). The demographic characteristics of the study sample are summarized in Table 1. The HIRI-MSM scores ranged from 8 to 33, with a median of 21.

Barriers to prep uptake
We grouped themes by structural, social, individual, and clinical factors that influenced barriers and opportunities to enhance PrEP uptake. Structural factors shape HIV risk via institutions, the environment, access to services and policy. Social factors affect HIV risk through interactions with others. [25][26][27][28] Individual factors are usually related to a person's decision-making, attitudes, or perspectives. Clinical factors include clinical issues a diagnosed bacterial sexually transmitted infection (STI) in the last 6 months. 19 Written informed consent approval was obtained from each participant prior to beginning study procedures. The study was approved by The Miriam Hospital Institutional Review Board. The research conforms to the principles of the Declaration of Helsinki.

Data collection
We conducted semi-structured, individual, in-depth interviews with HIV-negative, PrEP-naïve MSM who presented for HIV and STD screening services at an urban STD clinic in Providence, RI. Interviews were conducted by trained interviewers in a private room. Interviews lasted for approximately 45 min, were digitally recorded, and were professionally transcribed. We asked participants about their knowledge, opinions, and experience with PrEP, and identified barriers to PrEP uptake. We also solicited their normative recommendations about the essential components of a brief intervention to enhance PrEP uptake in STD clinics. Each participant received a $50 gift card.
These interviews assessed structural, social, individual, and clinical factors that may influence PrEP uptake among MSM who are indicated for PrEP but not currently taking it. Interview guides were informed by existing literature and the team's experience providing clinical services to this population. Interview guides contained questions about PrEP knowledge, including knowledge about PrEP relative to other HIV prevention interventions, attitudes about PrEP, and what factors might negatively or positively influence their PrEP use. To assess participants' HIV acquisition risk, we asked participants to complete the HIV Incidence Risk Index for MSM (HIRI-MSM), 20 which assesses risk by age group and sexual behaviors (i.e., condomless anal sex with one or more male partners). We solicited participant input about content for a brief intervention designed to promote PrEP uptake among MSM presenting to STD clinics. We also asked for their  that may impact a patient's experiences. Barriers included structural factors such as insufficient health care coverage and cost of medications; social factors such as stigma and fear of disclosure of one's sexual identify; individual factors such as the inaccurate self-perceived risk of acquiring HIV; and clinical factors (i.e., documented and perceived side effects) that may influence PrEP uptake (Table 2).

Structural barriers
Even among participants who were interested in taking PrEP, many identified insufficient health insurance coverage and expressed perceptions that high out-of-pocket costs precluded them from starting PrEP. While most were insured, many were unsure whether their insurance would cover PrEP costs.

I think PrEP is amazing. I just don't take it because I don't have health insurance.
Out of pocket for me, for one month, is basically the cost of the Participants were also concerned about unexpected costs at the pharmacy point of sale. One participant, still covered under his parent's insurance, was unclear whether his insurance plan covered PrEP. He noted his concerns about out-of-pocket costs: There's a lot of social stigma about not being able to afford things, so you know if I went to a pharmacy thinking that I was about to receive something and then be told it's a price I can't afford, that's something I would also want to avoid.

Social barriers
Some participants under the age of 26 and covered under their parents' health insurance were concerned that their parents would learn about their PrEP care through the explanation of benefits (EOBs) documents sent to their homes. This fear of disclosure about their sexual orientation and PrEP use to their parents precluded several participants from starting PrEP. Two participants explained:

Individual barriers
Prior to completing the HIRI-MSM, participants were asked to reflect and rate their selfperceived HIV acquisition risks. Many participants underrated their HIV acquisition risks, which were often incongruent with their scores on the HIRI-MSM. Underrating their acquisition risks was a key factor influencing men's decisions not to initiate PrEP. Two participants' comments illustrated this phenomenon:  put someone who is kind of in my position, where they're like "Oh, I don't really need it," in a place where they think, "well, it might be nice."

Normative suggestions for brief interventions to increase PrEP uptake in STD clinics
Participants offered important feedback about how to overcome barriers to PrEP uptake. Their suggestions included offering support to help patients obtain PrEP, tailoring the content and delivery of PrEP educational information to subpopulations of MSM, and providing culturally competent care for LGBTQ patients. They also commented on the preferred demographic characteristics of their PrEP providers.  Figure 1 presents the graphical representation of the effectiveness of different HIV prevention approaches used in our intervention. [29][30][31][32][33][34] In addition to including graphical representations of PrEP's efficacy in educational materials, participants appreciated the HIRI, a brief measure to help understand their own HIV acquisition risks. Participants also suggested that clinics routinely use and discuss the HIRI-MSM HIV-risk scale with patients.
Participants suggested providing information about PrEP's limited side effects. After suggesting this combination of interventions, one participant commented:

I feel good. I feel encouraged about taking it. I'd say it makes me more encouraged
to take it and more willing to take it than I would have been before. Not that I was unwilling to take it before -I just didn't know as much, but now that I know more, I'm more drawn to trying it out.
Another participant with similar suggestions suggested:

I think you should go through a participant's risk and then have a personal
conversation with someone about their prevention options. It's easier than sort of feeling that you're navigating this whole process and decision by yourself.

Service delivery recommendations
Participants suggested that culturally tailored messages about PrEP might enhance PrEP uptake, particularly for MSM of color. One African American participant from the Deep South remarked:

Structural recommendations
When asked how to best overcome the challenges of high copayments and deductibles, participants suggested having a navigator to help accurately forecast potential out-of-pocket costs, navigate patient assistance and copayment programs, and assist with associated paperwork. Two participants commented: I think it's helpful just to go through and have more of a personalized risk assessment. I think for my specific circumstances, the most helpful thing would be someone who'd be able to help navigate insurance stuff and figure this out with my providers, which I feel like is a large part of the medical system in general. I need a patient advocate.
It's nicer to just have a personal conversation with someone. I think it's pretty good. It's easier than feeling that you're navigating whole process and decision by yourself.

Recommendations for overcoming individual barriers
Most participants had incomplete knowledge about PrEP's efficacy, including its efficacy compared to other HIV prevention interventions, as well as the importance of daily medication adherence. They recommended developing a graphical illustration to help raise awareness about PrEP's efficacy relative to other HIV prevention interventions such as condom use, treatment as prevention, male circumcision, and changing sexual positions from receptive to insertive anal sex. Most participants did not have strong preferences about the gender, sexual orientation, or race of their health care providers. However, participants overwhelmingly noted their strong preferences for knowledgeable, non-judgmental, and gay-affirming providers, noting that these characteristics would impact their PrEP uptake. One participant remarked: The biggest point I would make about that is that whoever is providing these sessions should be understanding, sensitive, empathetic. As long as the person is culturally sensitive.
Another participant commented about the clinic's "safe space" culture: To identify as many barriers as possible to PrEP uptake, we developed a proposed list for participants to populate that could help a navigator to identify and overcome barriers to PrEP uptake (Figure 2).

DISCUSSION
Findings from this study suggest that structural, social, individual, and clinical factors may influence PrEP uptake among at-risk MSM presenting to urban safety-net STD clinics. Structural

comfortable and safe talking to the clinic staff about my sexual orientation and my partners.
A few participants expressed that having a clinical staff of their race, ethnicity, or sexual orientation may be important factors to retain MSM in PrEP care: Maybe subconsciously, like someone who is similar to you would probably be more appealing. If they're gay, as well, then I think I would feel more comfortable.

PrEPare to Start
Note: Circle your rating for each question/statement on the right.
PrEP stands for pre-exposure prophylaxis and is a pill taken once per day, every day to prevent HIV. We are trying to understand our clients' concerns about taking PrEP. What follow are some commonly cited reasons that people may be concerned about taking PrEP.
Please fill out this form so that we can understand any concerns you might have about taking PrEP. Our staff will then talk to you about any concerns you might have. Your answers will help improve the quality of care that we provide at this clinic.  factors affecting PrEP uptake were primarily financial, including prohibitive clinical and pharmaceutical costs for patients who were uninsured or underinsured. Social barriers included fear of disclosure of sexual identity and PrEP use. Individual factors included low perceived HIV-risk and a common unwillingness to take daily medications among otherwise healthy young men. Clinical barriers included perceived side effects and a lack of available educational information at provider locations. Participants offered numerous normative recommendations to enhance PrEP uptake, particularly among MSM of color. These included hiring PrEP navigators to address insurance and payment barriers, enhancing patient education by providing a graphical representation of PrEP's efficacy relative to other HIV prevention interventions, increasing the accuracy of patients' perceived HIV risk, and training providers and staff to give culturally competent PrEP education and care.
While few studies have explored barriers to PrEP uptake in STD clinics, our results are generally consistent with previous studies that examine barriers and facilitators to PrEP implementation and uptake in other clinical settings. [15][16][17] Barriers included patients' reluctance to take medication either because of perceived side effects with taking medication 14 or because of the inconvenience of taking daily medication when they were otherwise healthy; 22 low perceived HIV risk; [11][12][13] and the high and often variable cost of PrEP. 16 Previous research has also indicated that both the perceived and actual cost, particularly for uninsured and underinsured individuals, was an important barrier to PrEP uptake. 23 Perhaps, most importantly, participants offered numerous actionable solutions to overcome the aforementioned barriers that are highly applicable for busy real-world, high-volume STD clinics. To raise awareness about HIV acquisition risks, participants recommended a subjective HIV risk scoring instrument that could easily be self-administered during the intake process. 24 This tool could easily be self-administered by patients in busy STD clinics, and then presented to health care providers to shorten intervention time with each client. This might help mitigate inaccurate self-perceived HIV acquisition risks, which are major barriers to PrEP uptake. 25 While most participants had heard of PrEP, the overwhelming majority had limited knowledge about PrEP and its efficacy relative to other HIV prevention interventions. To address this concern, several participants suggested utilizing a graphical chart during the clinical intake process to help raise awareness about PrEP's efficacy relative to other HIV prevention interventions. We present this tool in Figure 1. Notably, participants' perceived side effects were also incongruent with actual side effects experienced by most patients. Participants' concrete suggestions to provide educational information about PrEP's relative efficacy and relatively few side effects could be delivered by clinical staff (e.g., nurses or nurse practitioners), via pamphlets, or on digital educational screens in the lobby. These low-cost efforts that require minimal human resource investment might enhance PrEP knowledge in busy clinical settings.
The most commonly cited barrier to PrEP uptake was the perceived out-of-pocket costs associated with deductibles and copayments for medications and clinical visits. Many participants did not know about industry and clinic-sponsored patient assistance programs and suggested that a navigator might help participants to overcome those cost barriers as well as navigate industry and clinic-sponsored patient assistance programs. Navigators might also enhance downstream outcomes in the PrEP continuum such as adherence and retention in PrEP care. 26 Additionally, navigators might help patients address concerns about stigma and disclosure with practical solutions. The proposed list for participants to populate that could help a navigator identify and overcome barriers to PrEP uptake is presented in Figure 2. While patient navigation can be costly, patient navigation for Ryan White patients has been associated with dramatic improvements in program uptake and clinical outcomes. Similar outcomes might be observed for PrEP participants. 27,28,35 Moreover, safety net STD clinics that offer 340B programs may be able to offset navigation costs with 340B revenue. 36 Another important vehicle for enhancing PrEP uptake in STD clinics is providing gay-affirming, culturally congruent care. Some participants seemed to have a preference for health care providers of their own racial or demographic background, but most participants noted their top priority was to have a gay-affirming, sex-positive provider who delivered care in a non-judgmental setting. Unlike the aforementioned suggestions, this suggestion may require cultural shifts and investment in capacity-building for culturally congruent care in some STD clinics. On the other hand, many STD clinics already have a gay-affirming, sex-positive culture, and may just need periodic training updates for providing culturally congruent PrEP care.
Our study is subject to several limitations, as it was based on a sample of MSM from an STD clinic in the Northeastern US. Thus, results may not be generalizable to other settings or other STD clinics. This study nevertheless offers several important findings for enhancing PrEP uptake in busy STD clinics. We found that complex social, structural, individual, and clinical factors impede PrEP uptake. However, inexpensive educational tools such as administering and reviewing an HIV risk score with patients, providing graphical educational materials about PrEP's relative efficacy in reducing HIV risks, and providing accurate information about PrEP's relatively few side effects might dramatically enhance PrEP uptake and help overcome many of these barriers. Other longer-term investments such as ongoing cultural competence training and patient navigation may also promote PrEP uptake in STD clinics. These findings have important implications for scaling up PrEP in STD clinics across the country. These suggested intervention components might also be easily combined into a "PrEP uptake toolkit" that