Factors associated with being PrEP-naïve among a US national cohort of former and naïve PrEP participants meeting objective criteria for PrEP care

Abstract

There is an urgent need to increase uptake and persistence in HIV pre-exposure prophylaxis (PrEP) in PrEP-eligible candidates. Little is known about the similarities and differences between groups of PrEP-naïve and former users; an important consideration for future interventions. We explored factors associated with being PrEP-naïve in a U.S. national cohort of naïve and former-PrEP users, all of whom met objective criteria for PrEP care at enrollment. Data were derived from the Together 5000 cohort study, an internet-based U.S. national cohort of cisgender and trans men and trans women who have sex with men. Participants were recruited via ads on men-for-men geosocial networking apps. All participants were not on PrEP at the time of enrollment. We conducted bivariate analysis to explore differences between the two groups and used multivariable logistic regression to assess factors associated with being PrEP-naïve. Of the 6283 participants, 5383 (85.7%) were PrEP-naïve, and 900 were former-PrEP users. There were significant differences between PrEP-naïve and former-PrEP users across multiple demographic variables, in addition to PrEP-related and psychosocial variables. Factors associated with being PrEP-naïve included younger age, sexual identity other than gay/queer, lower perception of candidacy for PrEP care, less willingness to take PrEP, lower access to PrEP-care, and individual-level barriers such as health- and provider-related concerns. Programs and policies designed to address uptake and persistence of PrEP should be aware of these differences. Providing care in non-traditional LGBTQ-care settings, home-based PrEP interventions, and provision by healthcare providers other than physicians could improve uptake. Future research should investigate mechanisms that can improve uptake and persistence in communities in need of PrEP.

Introduction

HIV continues to be a major epidemic in the United States, with over 38,000 new infections a year (CDC, 2017), and disproportionally impacting gay, bisexual men and other men who have sex with men (GBM). Pre-exposure prophylaxis (PrEP), in the form of emtricitabine and tenofovir disoproxil fumarate, is a FDA-approved once-daily pill that can provide near-full protection against HIV infection (McCormack et al., 2016). Since its approval in 2012, the effectiveness of PrEP has been consistently reaffirmed in both clinical and “real-world” settings; providing near-universal protection to HIV seroconversions, when adherence is high (Grant et al., 2010; Liu et al., 2016; McCormack et al., 2016; Volk et al., 2015).

The CDC estimates that approximately 1.2 million individuals would benefit from PrEP in the United States (Smith et al., 2015); however, fewer than 80,000 initiations were reported by 2016 (Ya-lin, Zhu, Smith, Harris, & Hoover, 2018). Communities of color, and communities across the southern United States, those already with disproportionate HIV incidence and significantly poorer HIV-related clinical outcomes (CDC, 2019), have been unequally impacted by access to, and information about PrEP (Smith, Van Handel, & Grey, 2018; Ya-lin et al., 2018). Systemic issues affecting MSM communities such as sexual stigma, discrimination, as well as psychosocial components like high levels of anxiety and depression are variables thought to explain the large gap between PrEP eligibility and uptake (Defechereux et al., 2016; Golub, 2018). Little is known, however, about how these variables are distributed in various groups of PrEP candidates. Understanding these metrics may better inform the development and deployment of PrEP resources seeking to enhance uptake and ultimately, persistence.

To measure progress in the HIV prevention continuum, studies have emphasized the use of PrEP motivational cascades (Kelley et al., 2015; Parsons et al., 2017), which are analogous and complementary to HIV treatment cascades in tracking progress along the continuum (Bradley et al., 2014). HIV cascades generally track milestones from seroconversion to viral suppression, while PrEP cascades track five prior milestones needed to avoid HIV acquisition:(1) objective eligibility for PrEP initiation, (2) willingness to take PrEP, (3) perception of candidacy for PrEP, (4) intention to initiate PrEP and (5) persistence in PrEP (Parsons et al., 2017). Thus far, PrEP motivational cascades have highlighted a disparate gap between an individual’s perception of being a candidate for PrEP versus their actual intention to initiate it; studies have reported high levels of candidacy perception and low levels of intention to start (Golub, Gamarel, Rendina, Surace, & Lelutiu-Weinberger, 2013; Parsons et al., 2017; Rendina, Whitfield, Grov, Starks, & Parsons, 2017). The use of cascades has thus become a standard measure for PrEP uptake over the years, with a specific focus on the narrowing of the perception-intention gap. Understanding the reasons for this gap, and how to best narrow it, may improve overall efforts to increase PrEP uptake, and to better tailor interventions for potential candidates. For example, it may be that individuals see PrEP as a good fit for themselves, but lack access to a competent PrEP provider; or perhaps individuals lack the financial resources to obtain the prescription.

Studies among PrEP-naïve candidates (i.e., someone who has never taken PrEP) have shown that age, income, level of education, perception of candidacy and perceived effectiveness have significantly predicted willingness and intention to initiate PrEP (Grov, Whitfield, Rendina, Ventuneac, & Parsons, 2015; Holloway et al., 2017; Rendina et al., 2017). Furthermore, PrEP-naïve candidates have indicated preferences for PrEP programs offering free coverage of the medication and access to supportive services (Golub et al., 2013). Individual-level barriers such as health-related concerns (Rendina et al., 2017) and communication of sexual health with medical providers (Golub et al., 2013; Rendina et al., 2017) have conversely been associated with unwillingness to start PrEP in naïve candidates. These findings have identified essential considerations for the development of interventions and programs targeting uptake in PrEP-naïve candidates.

Less studied is another critical group of individuals: former-PrEP users. To date, the majority of studies have described characteristics of groups of PrEP-naïve users with varying attitudes towards PrEP initiation (Golub et al., 2013; Grov et al., 2015; Parsons, Rendina, Whitfield, & Grov, 2016; Rendina et al., 2017). For PrEP to successfully impact the HIV epidemic, not only must uptake by naïve candidates increase, it likely needs to include high levels of persistence by current users. Although early PrEP demonstration projects reported high participant adherence and retention (Liu et al., 2016), “real-world” clinical settings have reported large PrEP discontinuation figures (37-62%) after six-months of use (Chan et al., 2016; Rusie et al., 2018; Scott et al., 2019). Given such large proportions of discontinuation, and short length of use, it is critical to understand the differences and similarities of these two groups. To date, no study has explored how the characteristics of former-PrEP users contrast to that of PrEP-naïve candidates, nor has any research compared the PrEP motivational cascade in both groups. For example, perception of candidacy in former PrEP-users remains unexplored, which prohibits a comprehensive understanding of issues around uptake and persistence. Similarly, a broader exploration of demographic, geographic and psychosocial differences between PrEP-naïve and former PrEP-users would better inform the development and deployment resources to communities in need. Understanding these factors is critical for the designing of tailored interventions and programs seeking to support the initiation of PrEP care in naïve candidates, and reengagement among those who may have discontinued. The following study seeks to understand differences in demographic, structural, PrEP-specific, and other characteristics in a national cohort of PrEP-naïve and former-PrEP GBM and transgender users meeting objective criteria for PrEP care. We additionally draw and discuss PrEP motivational cascades for both groups.

Methods

Data for this manuscript were from the Together 5,000 study, an internet-based U.S. national cohort of cisgender men, trans men, and trans women who have sex with men. Enrollment procedures for the study have been described in detail elsewhere.(C. Grov et al., 2019; Nash, in press) In brief, participants were enrolled via ads on men-for-men geosocial networking apps between October 2017 to June 2018. Participants clicking one of our ads were routed to a secure online survey where informed consent was obtained, and participants were screened for eligibility. This enrollment survey had no compensation.

Eligibility

To be eligible, participants had to self-identify as male, trans male or trans female; be aged 16 to 49; had to report at least 2 male sex partners in past 90 days; not currently be enrolled in a PrEP clinical study or an HIV vaccine trial; be living within the United States or its territories; not be taking PrEP at the time of enrollment; self-report an HIV status of negative or unknown; and meet at least one additional criteria out of the following: diagnosed with syphilis in the past 12 months, diagnosed with rectal gonorrhea/chlamydia in the past 12 months, shared injection drug use needles in the past 12 months, self-reported more than one receptive condomless anal sex (CAS) act with a man in the past 3 months, self-reported greater than two insertive CAS acts with a man in the past 3 months, took post-exposure prophylaxis (PEP) in the past 12 months, and/or self-reported methamphetamine use in the past 3 months. For participants under 18 years-old parental consent was waived.

In total, 8777 individuals met eligibility criteria. These participants were emailed and texted a link to an additional survey which included measures of interest in the present study. Those completing this second survey (n = 6283) were provided a $15 amazon.com gift card and are the analytic sample of the present manuscript.

Measures

Demographic Characteristics

Measures of interest for the present study included demographic characteristics. Age was collected in years and coded into the age groups (16-24, 25-29, 30-39, 40+). Race or ethnicity was collected categorically (White, Black/African American, Latino, Asian/Pacific Islander, multiracial). Gender identity was collected categorically as male, trans female, or trans male. Sexual identity was collected as gay/queer/homosexual, bisexual, straight/heterosexual, or other, and then coded into three groups (gay/queer, bisexual, straight/other). Lastly, annual income was collected as 11 categories from Less than $10,000 to $250,000 or more, in intervals of $10,000 to $50,000; this variable was recoded into 4 categories (< $20,000, $20,000 - $50,000, $50,000 - $100,000, $100,000+).

Access to Healthcare

Participants were asked about their health insurance status [Do you have health insurance?]; primary care provider (PCP) status [Do you have someone that you consider your primaiy care provider?]; those with a PCP, were asked whether their providers were aware of their sexual behavior [Does she or he know that you have sex with men?]. Variables were coded dichotomously (Yes/No).

PrEP Status

Participants were asked whether they had ever been prescribed PrEP before, “Have you ever been prescribed HIV medications (e.g, Truvada) for use as PrEP (Pre-Exposure Prophalyxis)?” Responses were, “I don’t know what PrEP is”, “I have never taken PrEP” or “Yes, but I am not currently taking PrEP.” We created a dichotomous variable—PrEP-naïve (i.e., never taken PrEP or does not know what PrEP is) and former-PrEP users—based on their answers. Participants who reported current PrEP use during the screening survey were not eligible for enrollment.

Perception of candidacy for PrEP care

Participants were presented with a brief description of PrEP:

“PrEP (pre-exposure prophylaxis) is a new biochemical strategy to prevent HIV infection. PrEP involves HIV-negative guys taking anti-HIV medications (for example, Truvada) once a day, every day to reduce the likelihood of HIV infection if they were exposed to the virus. PrEP is highly effective to reduce the likelihood of HIV infection. Please note that PrEP is not the same as taking HIV medications for a brief period of time (i.e., 28 days) after a high risk exposure to HIV through encounters such as being stuck by a contaminated needle or having unprotected intercourse. PrEP is intended for regular, long-term use.”

Following the prompt, they were asked their perceived candidacy for taking PrEP, “Do you believe that you are currently an appropriate candidate for PrEP?” The 5-categories response ranged from 1 “Yes, I am definitely an appropriate candidate for PrEP” to 5 “No, I am definitely not an appropriate candidate for PrEP.” Responses were recoded into a dichotomous variable yes (1-2) and unsure/no (3-5)

Willingness to take PrEP

Participants were also asked about their willingness to take PrEP, “Research shows that PrEP is at least 90% effective in preventing HIV when taken daily. How likely would you be to take PrEP if it were available for free?” There were 5 responses ranging from “I would definitely take it” to “I would definitely not take it.” We recoded all responses into a dichotomous variable (yes or unsure/no), where those who responded the top two affirmative answers were categorized as “yes” or willing to take PrEP, and those responding the bottom three negative or ambivalent answers were categorized as “unsure/no” or unwilling to take PrEP.

Intention to start PrEP

Participants were also asked about their intention to start PrEP care, “PrEP is currently available with a prescription from your doctor, and research has shown that a majority of insurance companies cover most or all of the costs. Do you plan to begin PrEP?” This measure was collected using a 5-item categorical variable with response options ranging from “I - Yes, I will definitely begin taking PrEP” to “5 - No, I definitely will not begin taking PrEP.” We combined those answering the first two affirmative options and those answering the last three categories to develop a dichotomous variable – “yes” or intending to start PrEP care or “unsure/no” or not intending or unsure “3 – I’m not sure – I might begin taking PrEP” about starting PrEP care.

Knowledge of a PrEP provider

Participants were also asked whether they generally know a medical provider they would feel comfortable requesting PrEP from [Suppose that you were interested in getting a new prescription for PrEP – do you have or know of a medical provider that you would feel comfortable asking to prescribe it for you?]. Responses to this question were recoded into a dichotomous variable (yes/no).

Anticipated Barriers to PrEP uptake

Participants completed as 12-item assessment about their concerns regarding anticipated barriers to taking PrEP (Golub et al., 2013; Rendina et al., 2017). Response options ranged from “1 - Not concerned at all” to “4 - Very Concerned.” Sample items included “The long-term effects of PrEP on my health,” “Bringing up the topic of PrEP with a doctor,” and “The way that men on PrEP are portrayed in the media.” We used an approach previously reported to develop 3 subscales: health consequences (range: 5-20; α = 0.88); provider concerns (range: 2-8; α = 0.91); and stigma (range: 4-16; α = 0.83). Subscales were computed by taking the average of their items.

Knowledge of people living with HIV

The enrollment survey asked participants about their knowledge of people living with HIV, using a numeric variable, “How many HIV-positive people do you know?” with options ranging from 0 – 90+. We recoded the variable to be dichotomous (yes/no) based on reporting knowledge of at least 1 person living with HIV.

Visiting a LGBTQ-affirming community center or health clinic in the past 6 months

Participants were asked about the number of times they visited various LGBTQ-affirming community centers or health care providers in the past 6 months. Categories ranged from “never” to “more than 10 times.” We developed a dichotomous variable (yes/no) by including anyone who answered any category other than “never” and visited either a community center or a healthcare provider in the past 6 months.

Individual Resilience

Resilience was measured using the 10-items Connor-Davidson Resilience Scale, which measures individual-level resilience (α = 0.88). Scale details have been reported elsewhere (Connor & Davidson, 2003).

Internalized Homophobia

A 14-item internalized homophobia scale, measuring internalized and subjective feelings of homophobia, was administered in our sample (α = 0.88). This scale has been described elsewhere (Herek, Cogan, Gillis, & Glunt, 1998).

Depression and Anxiety

Depression and anxiety was assessed in our sample (α = 0.91) by utilizing the 4-item PHQ-4 scale, previously validated. (Kroenke, Spitzer, Williams, & Löwe, 2009)

Analysis Plan

We compared PrEP-naïve and former-PrEP users on all variables selected for this study. Variables were selected to best describe the sample’s social determinants of health, such as their age, race and other demographic information. Additionally, we selected variables that described the sample’s structural access to health care, like their insurance status and access to a primary care provider, and variables that described their attitudes and feelings towards PrEP. Where appropriate, we conducted bivariate analysis to compare demographic, structural, PrEP-related and other differences between these two groups using chi-square tests of independence and t-tests. Next, we used a multivariable logistic regression model including all independent variables to explore associations between characteristics of PrEP-naïve participants, using the former-PrEP user group as reference.

Results

Of the 6283 participants, 5383 (85.7%) were PrEP-naïve, and 900 were former-PrEP users; their demographic and structural characteristics are described on Table 1. Our sample was mostly composed of people under the age of 30 (52%), nearly all cisgender male (98%) and self-identified as gay/queer (84%). Nearly half (48%) were non-White and the majority reported an income of $50,000 or less (75%). Nearly three quarters were insured, and 51% reported having a PCP. Among those with a PCP (n =3226), the majority (73%) reported that their provider was aware of their sexual behavior with men.

Table 1.

Demographic and Structural Characteritics differences among PrEP-Naïve and Former PrEP users

	Full Sample		PrEP-Naïve		Former-PrEP
	n= 6283		n= 5383		n= 900
Characteristic	n	%	n	%	n	%	χ2	p-value
Age							60.88	<0.001
16 – 24	1536	24.4%	1402	26.0%	134	14.9%
25 – 29	1735	27.6%	1470	27.3%	265	29.4%
30 – 39	2049	32.6%	1684	31.3%	365	40.6%
40+	963	15.3%	827	15.4%	136	15.1%
Gender Identity							2.86	0.09
Cisgender	6131	97.6%	5260	97.7%	871	96.8%
Transgender or non-binary	152	2.4%	123	2.3%	29	3.2%
Sexual Orientation							21.8	<0.001
Gay/Queer	5301	84.4%	4495	83.5%	806	89.6%
Bisexual	899	14.3%	811	15.1%	88	9.8%
Straight/Other	83	1.3%	77	1.4%	6	0.7%
Race/Ethnicity							7.39	0.12
White	3255	51.8%	2779	51.6%	476	52.9%
Black/African American	698	11.1%	603	11.2%	95	10.6%
Latinx	1543	24.6%	1343	24.9%	200	22.2%
Asian/Pacific Islander	226	3.6%	183	3.4%	43	4.8%
Multiracial	561	8.9%	475	8.8%	86	9.6%
Income							26.97	<0.001
< $20,000	2112	33.6%	1869	34.7%	243	27.0%
$20,000 - $50,000	2603	41.4%	2210	41.1%	393	43.7%
$50,000 – $100,000	1208	19.2%	993	18.4%	215	23.9%
$100,000+	360	5.7%	311	5.8%	49	5.4%
Has health Insurance							2.94	0.23
Yes	4554	72.5%	3883	72.1%	671	74.6%
No	1729	27.5%	1500	27.9%	229	25.4%
Has a Primary Care Provider							33.97	<0.001
Yes	3226	51.3%	2683	49.8%	543	60.3%
No	3057	48.7%	2700	50.2%	357	39.7%
PCP is aware of sexual behavior (n = 3226)							112.79	<0.001
Yes	2343	72.6%	1848	68.9%	495	91.2%
No	883	27.4%	835	31.1%	48	8.8%

For PrEP motivational cascade and LGBTQ community-related variables, shown in Table 2, most participants were willing to take PrEP (89%); however, with regards to the perception-intention gap, only 73% indicated they would be appropriate candidates for PrEP care, and three-quarters (75.6%) did not plan to begin PrEP care at all. See Figure 1. Although both groups had similar levels of willingness and intention to initiate PrEP, former users were significantly more likely to perceive themselves to be good candidates for PrEP than naïve participants. In total, 77% of our participants reported knowing at least one person living with HIV, and 40% visited an LGBTQ-affirming community center or clinic in the past six-months.

Table 2.

PrEP-Specific and LGBTQ Community related Variables differences among PrEP-Naïve and Former PrEP users

	Full Sample		PrEP-Naïve		Former-PrEP
	n= 6283		n= 5383		n= 900
Characteristic	n	%	n	%	n	%	χ2	p-value
Self-report PrEP Candidacy							83.25	<0.001
Yes	4599	73.2%	3828	71.1%	771	85.7%
Unsure/No	1684	26.8%	1555	28.9%	129	14.3%
Would take PrEP							0.31	0.58
Yes	5600	89.1%	4793	89.0%	807	89.7%
Unsure/No	683	10.9%	590	11.0%	93	10.3%
Plans to begin PrEP treatment							0.45	0.5
Yes	1536	24.4%	1324	24.6%	212	23.6%
Unsure/No	4747	75.6%	4059	75.4%	688	76.4%
Knows a provider that would feel comfortable asking for PrEP							233.6	<0.001
Yes	3440	54.8%	2736	50.8%	704	78.2%
No	2843	45.2%	2647	49.2%	196	21.8%
Has visited an LGBTQ community center, provider or facility							177	<0.001
Yes	2489	39.6%	1952	36.3%	537	59.7%
No	3794	60.4%	3431	63.7%	363	40.3%
Knows someone who is HIV-positive							75.35	<0.001
Yes	4868	77.5%	4070	75.6%	798	88.7%
No	1415	22.5%	1313	24.4%	102	11.3%

Figure 1. PrEP Motivational Cascade.

The figure above represents the PrEP motivational cascade from meeting objective criteria for PrEP care to indicating intention to start PrEP. We depicted our sample percentages by our groups of interest, PrEP-naïve and former-PrEP users. *p-value < 0.001

There were statistically significant differences between PrEP-naïve and former-PrEP users in our bivariate analysis, across multiple variables (all p < 0.001). A larger proportion of PrEP-naïve participants were younger, bisexual, straight or other, and reported lower income than former-PrEP users. Similarly, a greater proportion of PrEP-naïve participants did not have a PCP or knew a provider they felt comfortable asking for PrEP. Among participants with a PCP (n = 3226), a smaller proportion of PrEP-naïve patients had disclosed their sexual behavior to them. Per the enrollment criteria of the study, all participants met objective criteria for PrEP care; however, a smaller proportion of PrEP-naïve participants considered themselves good candidates. Further, a smaller proportion of PrEP-naïve participants knew a person living with HIV, and an even smaller proportion visited a LGBTQ affirming space in the past six-months. PrEP-naïve participants had significantly higher mean scores for all three subscales of anticipated barriers to PrEP uptake: stigma, provider concerns, and health consequences. They had also higher mean scores for internalized homophobia than former-PrEP users. See Table 3.

Table 3.

Individual Barriers to PrEP Subscales and Psychosocial Scales differences among PrEP-Naïve and Former PrEP users

	Full Sample		PrEP-Naïve		Former-PrEP
	n= 6283		n= 5383		n= 900
Scale	n	%	n	%	n	%	t-test	p-value
Barrier -Stigma ( Range: 5 -20)	7.3	3.4	7.4	3.4	6.7	3	6.28	<0.001
Barrier - Provider Concerns (Range: 2- 8)	3.9	2	4	2.1	3.1	1.6	13.32	<0.001
Barriers - Health Consequences (Range: 4 - 16)	10.6	3.3	10.7	3.3	10	3.3	5.81	<0.001
Connor-Davidson Resilience Scale	28.9	6.1	28.9	6.1	28.9	6	0.1	0.91
PHQ-4	4	3.6	3.94	6.7	4.17	3.7	1.7	0.077
Internalized Homophobia	26.6	7.9	26.76	7.9	25.65	7.6	3.91	<0.001

The results of our multivariable logistic regression are shown on Table 4. The likelihood of being a 16-24-year-old and having a sexual orientation other than gay/queer was significantly higher among PrEP-naïve participants compared to former-PrEP users. The odds of being PrEP-naïve in 16-24-year-old participants were 1.5-fold that of 25-29-year-old, and 1.75-fold of 30-39-year-old participants. Bisexual and straight or other sexual identity individuals had respectively 1.3 and 2.5 higher odds of being PrEP-naïve than gay participants. There was also a statistically significant lower chance of knowing someone living with HIV (aOR = 0.59); self-reporting being a good candidate for PrEP (aOR = 0.43); knowing a provider who they would feel comfortable asking for PrEP (aOR = 0.40); and having visited a LGBTQ affirming space in the past six-months among PrEP-naïve participants (aOR= 0.53). Lastly, PrEP-naïve participants were significantly more likely to report individual-level barriers to PrEP uptake related to health consequences and provider-related concerns than former-PrEP users.

Table 4.

Multivariable logistic regression predicting differences between PrEP-naïve participants and former-PrEP users

	Odds of being a PrEP-Naïve individual
	Reference: Former-PrEP Users
Characteristic	aOR	95% Confidence
Age (Ref: 16–24)
25 – 29	0.656**	0.52–0.83
30 – 39	0.571*	0.45–0.73
40+	0.83	0.62–1.11
Gender Identity (Ref: Cisgender)
Transgender or non-binary	0.74	0.47–1.17
Sexual Orientation (Ref: Gay/Queer)
Bisexual	1.298**	1.01–1.67
Straight/Other	2.534**	1.04–6.16
Race/Ethnicity (Ref: White)
Black/African American	0.98	0.75–1.26
Latinx	1.05	0.86–1.27
Asian/Pacific Islander	0.62	0.42–0.90
Multiracial	0.86	0.66–1.13
Income (Ref: < $20,000)
$20,000 - $50,000	0.88	0.73–1.06
$50,000 – $100,000	0.83	0.66–1.05
$100,000+	1.11	0.77–1.61
Has health Insurance (Ref: No)
Yes	1.01	0.83–1.22
Has a Primary Care Provider (Ref: No)
Yes	0.94	0.79–1.12
Knows someone who is HIV-positive (Ref: No)
Yes	0.594*	0.47–0.75
Self-report PrEP Candidacy (Ref: Unsure/No)
Yes	0.431*	0.35–0.54
Would take PrEP (Ref: Unsure/No)
Yes	1.09	0.83–1.42
Plans to begin PrEP treatment (Ref: Unsure/No)
Yes	1.12	0.94–1.34
Knows a provider that would feel comfortable asking for PrEP (Ref: No)
Yes	0.403*	0.33–0.49
Has vistie an LGBTQ community center, provider or facility (Ref: No)
Yes	0.533*	0.46–0.62
Barrier -Stigma ( Range: 5 -20)	1.00	0.97–1.03
Barrier - Provider Concerns (Range: 2- 8)	1.191*	1.13–1.26
Barriers - Health Consequences (Range: 4 - 16)	1.041*	1.02–1.07
Connor-Davidson Resilience Scale	1.01	0.99–1.02
PHQ-4	0.97	0.95–1.00
Internalized Homophobia	0.99	0.98–1.00

^*p < 0.001;

^**p < 0.05;

^***p < 0.01

Discussion

The ability of PrEP to effectively impact the HIV epidemic in the United States depends on both uptake and persistence among those who would benefit most from PrEP’s protection. Our findings show that there were significant differences between PrEP-naïve and former-PrEP users (all of whom met objective criteria for PrEP care at the time of enrollment) in our U.S. national cohort. These results underscore the importance of developing distinct strategies to engage new PrEP users and reengage former users. To our knowledge, this is one the first studies to assess structural, demographic, and PrEP-related differences between PrEP-naïve and former-PrEP GBM and transgender individuals in a national cohort of individuals meeting objective criteria for PrEP care.

Demographically, our results indicated that age and sexual orientation were important predictors of being PrEP-naïve. In fact, PrEP-naïve participants 16-24 years comprised over one quarter of that group compared to 15% of former-PrEP users. Younger age, specifically, seems to be a key consideration for interventions targeting uptake of PrEP – epidemiological surveillance has shown this group to face higher HIV incidence rates (CDC, 2017). Similarly having a sexual identity other than gay/queer was significantly associated with being PrEP-naïve, suggesting the need to expand the outreach and provision of PrEP outside of traditional LGBTQ-care places. Bisexual individuals, specifically, may benefit from receiving PrEP information targeted to their specific community, similar to what is currently done with transgender and African American cisgender women (Collier, Colarossi, & Sanders, 2017; Sevelius, Keatley, Calma, & Arnold, 2016). Furthermore, the integration of PrEP into the general primary care practice is and should continue to be at the forefront of efforts to increase uptake in naïve candidates (Calabrese, Krakower, & Mayer, 2017); such efforts can help streamline a regular discussion of PrEP and sexual health to the general population. Our results also suggest that other approaches, some already underway, to offering PrEP in non-healthcare spaces where young people may access healthcare services, such as in community based organizations, via the internet, or in home-based services models could help improve uptake and warrants further investigation. (Siegler et al., 2019; Touger & Wood, 2019)

Our sample had high levels of willingness to take PrEP (89%). Despite that, only about three-quarters (73.2%) of our participants considered themselves PrEP candidates, and only one quarter (24.4%) planned on initiating PrEP care, though the entire sample met objective criteria for it. The persistent perception-intention gap has been observed elsewhere. In two studies, whereby the sample was also restricted to just GBM who met objective criteria for PrEP care, researchers found that about 50% perceived themselves to be appropriate candidates for PrEP (whereas in our sample it was 75%) (Parsons et al., 2017; Rendina et al., 2017). Interestingly, however, intentions to begin PrEP in both those studies as well as ours was the same at approximately 25%. It may be that differences in perceived candidacy for PrEP care (i.e., believing oneself an appropriate candidate for PrEP) across those studies and ours could be due to increased familiarity of PrEP over time (Rendina et al. and Parsons et al. were collected 2014, whereas our data were collected 2017-2018, during a time in which PrEP is more a part of the HIV prevention lexicon). However, the large gap between meeting objective criteria for PrEP and intentions to start PrEP observed in our sample suggest an urgent need to consider strategies to offering PrEP that are not solely based on objective clinical guidelines. Researchers recently discussed strategies to mitigate the perception-intention gap, for example, by using PrEP as a way to reduce HIV-related anxiety and focusing on the role of PrEP in increasing partner intimacy (Golub & Myers, 2019). Strategies like these, addressing issues other than risk for HIV acquisition itself, could prove very effective in further closing the larger gap between eligibility for PrEP and intention to initiate PrEP care. Intimacy motivation, specifically, has been previously reported as a significant predictor of intention to start PrEP (Gamarel & Golub, 2015), indicating that the uptake of PrEP is not simply conditioned on HIV prevention. A deeper understanding of this framework will better inform ways to expand the criteria for PrEP beyond objective risk, and further increase the pool of candidates who perceive PrEP as beneficial for them.

Currently, in the U.S., guidelines for PrEP eligibility are based solely in clinical objectivity (i.e., having a STI; having a partner living with HIV), and while these are appropriate tools to guide medical practice, they are not enough. In our study, PrEP-naïve participants had, on average, significantly higher internalized homophobia mean scores than former-PrEP users; they were also significantly more likely not to perceive themselves as PrEP candidates, and to report more stigma-related barriers (i.e., concerned about how gay men on PrEP are portrayed in the media). While our findings cannot establish a causal pathway between experiences of discrimination and PrEP uptake, they illustrate a potential mechanism for which these experiences may impact uptake, especially in PrEP-naïve candidates. Systemic structural issues like discrimination, stigma, homophobia and transphobia are important factors fueling the HIV epidemic in the U.S., (Denning, DiNenno, & Wiegand, 2011; Gupta, Parkhurst, Ogden, Aggleton, & Mahal, 2008) and implementation strategies may benefit from addressing these issues along with PrEP promotion. Future research should further investigate how experiences of discrimination and stigma may impact PrEP uptake.

Lastly, PrEP-naïve participants were significantly more likely to report concerns related to health consequences about PrEP (e.g., side effects, partial protection) as well as concerns communicating sexual health to medical providers than former-PrEP users. Earlier cohorts of PrEP-naïve candidates have already demonstrated that among those intending to start PrEP, concerns related to provider communication were prevalent (Rendina et al., 2017). Interventions to facilitate communicating about HIV prevention and sexual behavior with medical providers are necessary to efforts aiming to enhance uptake in PrEP-naïve candidates and need to be scaled-up. Alternative methods to deliver PrEP, such as through nurses (O'Byrne, MacPherson, Orser, Jacob, & Holmes, 2019), pharmacists (Ryan, Lewis, Sanchez, Anderson, & Mercier, 2018) or telehealth (Touger & Wood, 2019) could help overcome some of these concerns by linking candidates to other medical professionals who they may feel more comfortable asking questions and receiving care. Similarly, home-based PrEP services could be an alternative way to address such concerns. Research around preferences for home-based PrEP showed that candidates with higher provider-related concerns (i.e., bringing up the topic of PrEP) were more likely to prefer home-based PrEP services (John, Rendina, Grov, & Parsons, 2017).

Limitations

Our results should be understood in light of their limitations. First, items were self-reported and could be subject to social desirability—although self-administered surveys (as opposed to interviewer-administered) can reduce social desirability. (King & Bruner, 2000) Additionally, data were from a cross-sectional assessment and some variables, such as sexual risk assessment, may be limited to the context of the participant during the period of data collection and causality cannot be inferred. Similarly, additional variables that could further explain differences in our analysis may have not been measured. For instance, we lacked sufficient information about why participants stopped using PrEP – an area where further research is needed. Lastly, although our sample was nationwide, our recruitment strategies did not produce a US-representative sample of GBM nor transgender individuals. Instead, our recruitment was conducted via geo-social dating apps, and designed to identify individuals at risk for HIV.

Conclusions

Our findings demonstrated that there were distinct differences between PrEP-naïve and former-PrEP users that meet objective criteria for PrEP care. We found that participants who were PrEP-naïve were more likely to be younger, have lower socioeconomic status, and have more limited access to healthcare. Additionally, individual-level barriers, and lower self-assessment of eligibility were significantly associated with being PrEP-naïve. Overall, a majority of our participants, all of whom met objective criteria for PrEP care, agreed that they were good candidates for it; however, an overwhelming majority did not have plans to initiate it. These findings suggest that alternatives to daily-PrEP, other types of PrEP-implementation strategies, and likely other types of PrEP dosing and formulations may be beneficial for communities with low uptake of daily-PrEP. Distinct interventions that target specific groups are likely needed to support uptake or initiation of PrEP and future research should focus on exploring specific tools, interventions and structural features that may influence uptake of and support persistence on PrEP.