Opinions and Concerns Surrounding Long-Acting Injectable (LAI) and Oral HIV Pre-exposure Prophylaxis (PrEP) Among Current and Former LAI and Oral PrEP Users

Abstract

Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) has potential to increase PrEP uptake and adherence. However, most studies investigating opinions about LAI PrEP were done prior to its approval. We administered a cross-sectional electronic survey to clients at an urban PrEP clinic in the U.S. South. Eligible participants were 18 + and had previously taken or been prescribed oral or LAI PrEP. They were asked their opinions on PrEP, barriers to access, perceived HIV risk, and PrEP stigma. Between January and April 2024, 123 people participated. Twenty-two (17.9%) used LAI PrEP, 80 (65.0%) oral PrEP, and 21 (17.1%) were not currently using PrEP. Most participants identified as men (87.8%), and mean age was 38.6 (range 19–78). Participants were 52.8% White, 27.6% Black, and 14.6% Latinx. 56.1% preferred injection versus daily oral pill. Common concerns about PrEP included side effects (n = 48), cost of medication (n = 21), and cost of clinic visits/tests (n = 21). Of those taking oral PrEP, 56.3% reported remaining on oral because LAI was not offered to them and/or they were not aware of it. Perceived HIV risk scores were on average higher for those not currently taking PrEP (not on = 26.8, SD = 6.54; LAI = 22.3, SD = 6.45; oral = 24.2, SD = 6.13). Overall, participants had low to moderate PrEP stigma scores. Despite majority preference for LAI PrEP, patients are frequently unaware of or not offered LAI. Common concerns about PrEP include side effects and costs. These data demonstrate the importance of improving LAI PrEP awareness and accessibility of choice.

Supplementary Information

The online version contains supplementary material available at 10.1007/s10461-025-04749-0.

Introduction

Pre-exposure prophylaxis (PrEP) is an effective and important tool to prevent HIV acquisition [1]. Oral forms of PrEP have been available since 2012 but come with potential barriers to use including side effects and challenges in adhering to a daily regimen [2, 3]. PrEP clinics have shown low rates of patient retention in care even after just six months [4, 5]. Some of these challenges may be addressed by the approval of long-acting injectable (LAI) PrEP with injectable cabotegravir in 2021 by the Federal Drug Administration (FDA). LAI PrEP provides patients an effective and desirable form of HIV prevention, in large part due to improved adherence, reduced stigma, and the ease of a bimonthly regimen [6–8]. However, it also brings unique barriers—namely high cost depending on insurance status and medical benefits and injection-specific adverse effects [9–11].

Previous studies have shown high interest in LAI PrEP among oral PrEP users and people who are at increased risk of HIV acquisition [12–14]. These studies also indicated that knowledge of LAI PrEP, and PrEP in general, remains low [15]. Additionally, there is wide variation in the priorities of people who would benefit from PrEP resulting in heterogeneity in PrEP preferences [10, 12]. However, the majority of research focusing on LAI PrEP was conducted before FDA approval of LAI PrEP or before it was accessible at clinics. Participants were often presented with theoretical choices in preference studies which did not always match the real-world barriers patients face or the dosing schedule that was eventually approved for the cabotegravir form of LAI PrEP. Research that includes participants who are currently using LAI PrEP remains limited. Moreover, there is a gap in the literature surrounding the opinions about oral and LAI PrEP of patients who have stayed on oral PrEP or who have stopped taking PrEP since FDA approval of LAI PrEP.

The purpose of this study was to explore opinions, concerns and barriers to accessing PrEP, as well as differences in perceived HIV risk and PrEP stigma, among patients who are currently taking oral or LAI PrEP or who have taken or been prescribed PrEP in the past but are not currently on PrEP. We hypothesized that higher perceived risk of HIV would correlate with increased interest in starting LAI PrEP.

Methods

Study Design

This was a cross-sectional electronic survey on participants’ current and prior experience with PrEP, conducted between January 10 and April 24, 2024, at a PrEP clinic in an academic health center in North Carolina. The research setting was chosen by convenience. Participants responded to a one-time online Qualtrics^® survey on a clinic-provided tablet in person, or through a link sent via the electronic medical record (EMR), text, or email.

Setting and Subjects

Eligible participants were 18 years or older and were currently or previously taking PrEP (including oral tenofovir alafenamide or tenofovir disoproxil fumarate in combination with emtricitabine, and/or injectable cabotegravir), or were previously prescribed PrEP but never began taking the medication. Participants with current or past usage of oral or injectable PrEP were identified through the EMR. Those with appointments at the PrEP clinic within the recruitment window were approached during their in-person appointments; otherwise, survey participants were invited through a combination of EMR messages and phone calls. For the purposes of anonymity, method of recruitment was not tracked in survey responses, and analyses were not done to compare methods. At the end of the survey, participants were able to voluntarily register for a raffle of one of five $50 Amazon gift cards.

Data Collection

The survey had a total of 50 items (Appendix 1). Each participant answered approximately 40 items, but total number varied as items were hidden with branching logic based on respondent’s prior and current PrEP usage. For example, participants currently on PrEP were not shown items regarding reasons for stopping PrEP. Informed consent to participate and participant age were obtained at survey onset. Participants were then presented with a short overview passage explaining what PrEP is used for and the difference between oral and LAI methods of PrEP. They were also asked about their sex, gender, sexual orientation, race, ethnicity, relationship status, sexual activity in the last 6 months, educational attainment, insurance status, and type and length of time on PrEP. All participants were asked about their preference for either oral or injectable PrEP. Persons who were prescribed PrEP but never filled their prescription or who were not currently on PrEP were also asked about their interest in starting or restarting oral or injectable PrEP.

Concerns About and Barriers to Accessing PrEP

All participants were asked about their general concerns about PrEP. Additionally, participants who never filled their prescription or were not currently on PrEP were asked about reasons they did not fill or stopped PrEP. Participants who were currently on oral or injectable PrEP were asked about reasons they chose their current form over the other option.

Perceived HIV Risk

Perceived risk of HIV was assessed using the perceived risk of HIV infection scale [16]. An 8-question version provided by the senior author (Fisher) was used in the survey in order to reduce question burden. The tool was slightly amended to include “neither likely nor unlikely” as an answer option to one of the questions. Using the scale, participants were assigned a summative score with higher scores representing greater risk perception. Possible scores ranged from 10 to 40. Participants were excluded if they did not answer all eight questions given the summative nature of the score.

PrEP Stigma

PrEP stigma was assessed using an adapted version of the PrEP stigma scale [17]. To reduce question burden, the scale was shortened based on suggestions from the first author and scale designer (Siegler). Eight statements were selected to design the scale, one from each of eight stigma framework categories. The statements with the highest item-rest correlation were chosen. Answers were given as Likert scale responses and scales were coded so that higher values equated to higher stigma. Overall PrEP stigma scores were calculated by averaging participants’ responses on the stigma scale and possible scores ranged from 1 (indicating low stigma) to 5 (indicating high stigma). Participants were excluded if they did not answer all eight questions.

Open Response Field

Participants were also given an optional open response field at the end of the survey to leave comments and feedback.

Data Analysis

Descriptive statistics were used to analyze demographics, barriers to accessing different forms of PrEP, perceived HIV risk scale, and PrEP stigma scale. A logistic regression analysis was conducted to test the hypothesis that higher perceived HIV risk, adjusted for time on PrEP (either more or less than one year) and relationship status, would be associated with increased odds of preference for LAI PrEP. Variables included in the multivariate model were selected based on a literature review identifying key factors influencing PrEP use. Time on PrEP was included due to evidence of a significant drop-off in retention in care after approximately one year [4, 5], and relationship status was included as partner dynamics can impact PrEP use [18].

Due to the exploratory nature of the study and sample size constraints, additional variables such as age and education level were not controlled for in the model. The regression analysis included only participants who were currently using oral PrEP. Participants not on PrEP were excluded due to their small sample size, and those already using LAI PrEP were excluded due to their overwhelming preference for injectable PrEP. Participants who selected ‘no preference’ were classified as preferring daily oral PrEP.

For the regression analysis, statistical significance was determined at the standard alpha value of 0.05. Regression residual assumptions were checked using a binned residual plot. Collinearity between independent variables was evaluated using chi-square tests (for relationship status vs. length of time on PrEP) and variance inflation factor (for other independent variables). Data was not weighted for analysis and given the cross-sectional design, findings were purely associative. All analyses were performed within R.

Ethical Approval

Measures used in the survey were developed in collaboration with the Duke Collaborative Community Council (DC3), a group of research-engaged community members in North Carolina who promote HIV prevention and care and work closely with the Duke Center for AIDS Research. This study was approved by the Duke University Institutional Review Board. There were no external funding sources. We acknowledge that this survey, like all forms of public opinion research, faces limitations and unseen sources of error for which we cannot completely account.

Results

Demographics

Eighty-seven people were approached during in-person PrEP clinic visits and of those, 76 (87%) participated in the survey. An additional 332 people were sent messages on the EMR patient portal and/or phone calls and of those, 47 (14%) participated in the survey.

In total, 123 people participated in the survey. Among survey participants, 22 (18%) were currently using LAI PrEP, 80 oral PrEP (65%), and 21 (17%) were not currently on a form of PrEP (Table 1). Average age of the participants was 38.6 years old (range 19–78, SD = 13.1). The majority of participants identified as men (n = 108, 87.8%) and as gay (n = 82, 66.7%) or bisexual (n = 13, 10.6%). Additionally, 52.8% (n = 65) identified as White, 27.6% (n = 34) as Black, with 3.3% (n = 4) selecting multiple self-reported race categories. In our study, 14.6% (n = 18) of participants identified as Latinx. Most of the participants were single (n = 71, 57.7%) and sexually active with one or more new partners in the last six months (n = 85, 69.1%). Nearly 70% (n = 85) reported having completed a college degree and another 25.2% (n = 31) had completed a high school degree or some college. The majority of participants were privately insured (n = 85, 69.1%), either through their employer or the healthcare.gov market. Some participants were insured through Medicaid (n = 12, 9.8%) or Medicare (n = 2, 1.6%) and nine (7.3%) reported having multiple forms of insurance. Only three participants (2.4%) reported having no insurance. A large proportion of patients on oral PrEP had taken oral PrEP for more than 3 years (n = 35, 43.8%). The three groups were generally similar, with the exception of those not currently on PrEP being on average younger (not on PrEP: mean = 35.2 years, SD = 12.4; LAI: mean = 40 years, SD = 13.6; oral: mean = 39 years, SD = 13.1), with fewer identifying as men (not on PrEP: 71.4%; LAI: 90.9%; oral: 91.3%) and fewer Black (not on PrEP: 14.3%; LAI: 31.8%; oral: 30.0%).

Table 1.

Demographic and clinical characteristics of survey participants

	Overall (N = 123)	Not Currently on PrEP (N = 21*)	LAI PrEP (N = 22)	Oral PrEP (N = 80**)
Age
Mean (SD)	38.6 (13.1)	35.2 (12.4)	40 (13.6)	39 (13.1)
Median (Q1, Q3)	35 (29, 46)	33 (27, 40)	34 (30.2, 49.2)	36.5 (29, 46.2)
Min, Max	19, 78	19, 73	22, 71	19, 78
Months on LAI PrEP
Mean (SD)	–	–	14.9 (17.7)	–
Median (Q1, Q3)	–	–	9 (6.25, 14.8)	–
Min, Max	–	–	0, 72	–
Time on oral PrEP
Less than 1 year	–	–	–	19 (23.8%)
1–3 years	–	–	–	25 (31.3%)
Over 3 years	–	–	–	35 (43.8)
Missing	–	–	–	1 (1.3%)
Gender
Man	108 (87.8%)	15 (71.4%)	20 (90.9%)	73 (91.3%)
Non-binary or gender fluid	3 (2.4%)	1 (4.8%)	1 (4.5%)	1 (1.3%)
Trans man	1 (0.8%)	1 (4.8%)	0 (0%)	0 (0%)
Trans woman	1 (0.8%)	0 (0%)	0 (0%)	1 (1.3%)
Woman	5 (4.1%)	2 (9.5%)	1 (4.5%)	2 (2.5%)
Missing	5 (4.1%)	2 (9.5%)	0 (0%)	3 (3.8%)
Sex
Female	6 (4.9%)	3 (14.3%)	1 (4.5%)	2 (2.5%)
Male	112 (91.1%)	16 (76.2%)	21 (95.5%)	75 (93.8%)
Missing	5 (4.1%)	2 (9.5%)	0 (0%)	3 (3.8%)
Sexual orientation
Bisexual	13 (10.6%)	2 (9.5%)	5 (22.7%)	6 (7.5%)
Gay	82 (66.7%)	13 (61.9%)	13 (59.1%)	56 (70.0%)
Heterosexual/straight	4 (3.3%)	1 (4.8%)	1 (4.5%)	2 (2.5%)
Pansexual	2 (1.6%)	0 (0%)	0 (0%)	2 (2.5%)
Queer	5 (4.1%)	2 (9.5%)	0 (0%)	3 (3.8%)
Multiple	10 (8.1%)	0 (0%)	3 (13.6%)	7 (8.8%)
A sexual orientation not listed here	2 (1.6%)	1 (4.8%)	0 (0%)	1 (1.3%)
Missing	5 (4.1%)	2 (9.5%)	0 (0%)	3 (3.8%)
Hispanic/Latinx ethnicity
No	100 (81.3%)	16 (76.2%)	20 (90.9%)	64 (80.0%)
Yes	18 (14.6%)	3 (14.3%)	2 (9.1%)	13 (16.3%)
Missing	5 (4.1%)	2 (9.5%)	0 (0%)	3 (3.8%)
Race
American Indian or Alaskan Native	2 (1.6%)	1 (4.8%)	0 (0%)	1 (1.3%)
Asian/Pacific Islander	3 (2.4%)	1 (4.8%)	1 (4.5%)	1 (1.3%)
Black/African American	34 (27.6%)	3 (14.3%)	7 (31.8%)	24 (30.0%)
White/Caucasian	65 (52.8%)	10 (47.6%)	11 (50.0%)	44 (55.0%)
Multiple	4 (3.3%)	1 (4.8%)	1 (4.5%)	2 (2.5%)
A race not listed here	2 (1.6%)	0 (0%)	0 (0%)	2 (2.5%)
Prefer not to answer	5 (4.1%)	3 (14.3%)	1 (4.5%)	1 (1.3%)
Missing	8 (6.5%)	2 (9.5%)	1 (4.5%)	5 (6.3%)
Relationship status
Partnered with one or more people	45 (36.6%)	8 (38.1%)	9 (40.9%)	28 (35.0%)
Single	71 (57.7%)	9 (42.9%)	13 (59.1%)	49 (61.3%)
Missing	7 (5.7%)	4 (19.0%)	0 (0%)	3 (3.8%)
Sexual activity in last six months
Sexually active, no new partners	24 (19.5%)	5 (23.8%)	6 (27.3%)	13 (16.3%)
Sexually active, and I have had one or more new partner(s)	85 (69.1%)	12 (57.1%)	15 (68.2%)	58 (72.5%)
Not sexually active	8 (6.5%)	2 (9.5%)	1 (4.5%)	5 (6.3%)
Prefer not to answer	1 (0.8%)	0 (0%)	0 (0%)	1 (1.3%)
Missing	5 (4.1%)	2 (9.5%)	0 (0%)	3 (3.8%)
Highest level of education completed
Less than high school degree	2 (1.6%)	1 (4.8%)	0 (0%)	1 (1.3%)
High school degree or equivalent	11 (8.9%)	1 (4.8%)	1 (4.5%)	9 (11.3%)
Some college, but no college degree	20 (16.3%)	4 (19.0%)	6 (27.3%)	10 (12.5%)
Completed college degree	85 (69.1%)	13 (61.9%)	15 (68.2%)	57 (71.3%)
Missing	5 (4.1%)	2 (9.5%)	0 (0%)	3 (3.8%)
Insurance
Medicaid	12 (9.8%)	1 (4.8%)	3 (13.6%)	8 (10.0%)
Medicare	2 (1.6%)	0 (0%)	1 (4.5%)	1 (1.3%)
Private insurance - healthcare.gov market	7 (5.7%)	1 (4.8%)	0 (0%)	6 (7.5%)
Private insurance - employer	78 (63.4%)	14 (66.7%)	13 (59.1%)	51 (63.8%)
Multiple	9 (7.3%)	1 (4.8%)	1 (4.5%)	7 (8.8%)
Other	5 (4.1%)	1 (4.8%)	1 (4.5%)	3 (3.8%)
None	3 (2.4%)	0 (0%)	2 (9.1%)	1 (1.3%)
Missing	7 (5.7%)	3 (14.3%)	1 (4.5%)	3 (3.8%)

*Of 21 participants not on PrEP, 20 were previously on PrEP; one was prescribed PrEP but did not start

**Oral PrEP included patients who had taken either tenofovir alafenamide or tenofovir disoproxil fumarate in combination with emtricitabine. We did not ask which one

Preference for Oral vs LAI PrEP

Overall, most participants (56.1%) preferred injection over daily pill when asked to choose between the two methods. Participants currently using LAI overwhelmingly chose injection (n = 22, 100%). About half of participants not currently using PrEP also preferred injection (n = 11, 52.4%). Of participants who were using oral PrEP, 45.0% (n = 36) preferred injection, 37.5% (n = 30) preferred a daily pill, and 10.0% (n = 8) had no preference. Additionally, 56.3% (n = 45) of participants taking oral PrEP reported that they had not switched to injectable PrEP either because it was not offered to them (n = 35, 43.8%) or they were not aware of LAI before taking this survey (n = 15, 18.8%). Another 15% (n = 12) reported that insurance would not cover LAI PrEP. The most common reason for those on LAI choosing injection over oral was not wanting to take a pill every day (n = 21, 95.5%), followed by feeling that the injectable form was more effective (n = 14, 63.6%).

Participant Concerns About and Barriers to Accessing PrEP

The most common concern across all three PrEP modality groups were side effects of PrEP (n = 48, 39.0%) (Fig. 1). Other common concerns included cost of clinic visits or testing (not on PrEP: n = 5, 23.8%; LAI: n = 3, 13.6%; oral: n = 13, 16.3%), cost of PrEP (not on PrEP: n = 4, 19.0%; LAI: n = 4, 18.2%; oral: n = 13, 16.3%), and having to take a pill every day (not on PrEP: n = 4, 19.0%; LAI: n = 4, 18.2%; oral: n = 9, 11.3%). Patients currently taking either form of PrEP also reported concerns that if they became HIV+, certain medicines would not work because of taking PrEP (not on PrEP: n = 1, 4.8%; LAI: n = 4, 18.2%; oral: n = 13, 16.3%). Importantly, a little over a quarter of overall participants cited having no concerns about PrEP (n = 33, 26.8%). When asked about reasons why participants who were not currently on PrEP had stopped using the medication, the most common reasons included no longer needing PrEP (n = 7, 33.3%) and side effects (n = 5, 23.8%).

Fig. 1.

General concerns about PrEP amongst participants not currently on, on LAI or on oral PrEP

Perceived Risk of HIV

Participants who were not currently on PrEP had on average higher scores (mean = 26.8, SD = 6.54) than those on either form of PrEP. Those on LAI and oral PrEP had similar risk perception scores, with oral being slightly higher (LAI: mean = 22.3, SD = 6.45; oral: mean = 24.2, SD = 6.13). Overall, participants had a moderate amount of perceived HIV risk with an average score of 24.2 (SD = 6.32; moderate amount as described by Napper et al. [16]).

Relationship Between Preference for LAI PrEP and Perceived Risk of HIV, Time on ORAL PrEP, and Relationship Status

Consistent with our hypothesis, we ran a multivariate model to test whether preference for LAI PrEP was associated with higher perceived HIV risk while controlling for time on oral PrEP and relationship status. Participants who had used oral PrEP for one year or more had significantly lower odds of preferring LAI than participants who had been on oral for less than one year (OR = 0.18, CI = 0.05–0.61, p = 0.008; Table 2). Additionally, when adjusting for time on oral PrEP and perceived risk of HIV, being partnered with one or more people (compared to being single) was associated with nearly three times higher odds of preferring injectable (OR = 2.98, CI = 1.04–9.12, p = 0.047). However, higher perceived HIV risk was not significantly associated with higher odds of preferring injectable over oral PrEP. These results remained unchanged in a sensitivity analysis excluding the 8 participants who reported no preference.

Table 2.

A multivariate model resulting in estimated odds ratios predicting the association of preference for injectable PrEP with relationship status, time on pill, and perceived HIV risk score for participants on oral PrEP

Independent Variable		Preference for Daily pill (n = 38*)	Preference for Injection every 2 months (n = 34*)	Odds Ratio**
Relationship status	Single	28 (59.6%)	19 (40.4%)	∙
∙	Partnered with one or more people	10 (40.0)	15 (60.0)	2.98 (1.04–9.12, p = 0.047)
Time on pill	Less than 1 Year	5 (27.8)	13 (72.2)	∙
∙	More than 1 Year	33 (61.1)	21 (38.9)	0.18 (0.05–0.61, p = 0.008)
Perceived HIV risk score	Mean (SD)	24.3 (5.9)	24.1 (6.5)	0.99 (0.91–1.08, p = 0.797)

*Participants on LAI PrEP and not currently on PrEP were not included in regression analysis due to small sample sizes and for those on LAI, the overwhelming preference for injectable

**Odds ratios included here represent the predicted preference for LAI for each independent variable controlling for the other two independent variables

PrEP Stigma

Stigma scores indicated generally low to moderate average stigma scores overall (1.97; SD = 0.598) and were similar between the three groups with the average score being 1.94 (SD = 0.476) for those not currently on PrEP, 2.09 (SD = 0.626) for those on LAI, and 1.94 (SD = 0.62) for those on oral (Table 3). Almost all participants either agreed or strongly agreed with the statements regarding positive connotations of PrEP, but there was more variation on the statements with negative connotations (Fig. 2). Moreover, numerous participants left comments in the open response field indicating stigmatizing beliefs surrounding PrEP. These comments included statements such as, “I feel that people on PrEP have to be mindful that there are drug-resistant strands of HIV and that PrEP and PEP are not whore pills,” and “PrEP I believe has been a blessing and a curse. I feel a lot more people are indulging in risky behavior because of PrEP.” On the other hand, other participants were very positive about PrEP, stating “I think it’s an awesome drug,” and “PrEP has given me a peace of mind I desperately needed, and I have no regrets about taking my daily pill.”

Table 3.

PrEP stigma and HIV risk scores for survey participants

	Overall (N = 123)	Not Currently on PrEP (N = 21)	LAI PrEP (N = 22)	Oral PrEP (N = 80)
PrEP stigma score
Mean (SD)	1.97 (0.598)	1.94 (0.476)	2.09 (0.626)	1.94 (0.62)
Median (Q1, Q3)	2 (1.5, 2.28)	2 (1.62, 2.12)	2.12 (1.78, 2.5)	1.88 (1.5, 2.31)
Min, Max	1, 3.8	1.2, 3.1	1, 3.2	1, 3.8
Missing	7 (5.7%)	2 (9.5%)	0 (0%)	5 (6.3%)
Perceived HIV risk score
Mean (SD)	24.2 (6.32)	26.8 (6.54)	22.3 (6.45)	24.2 (6.13)
Median (Q1, Q3)	24 (20, 29)	28 (23, 30.2)	22 (17.5, 26)	24 (20, 29)
Min, Max	10, 38	14, 38	13, 36	10, 37
Missing	8 (6.5%)	5 (23.8%)	0 (0%)	3 (3.8%)

Population includes entire study sample

Fig. 2.

PrEP stigma statement agreement levels by current PrEP usage status. ^aAnswers coded in orange represent more stigmatizing responses, participants who responded to any number of the eight items were included in this figure

Discussion

Given the recent FDA approval of LAI PrEP, this is among the first surveys to be conducted outside of a clinical trial that includes participants currently on LAI PrEP and those receiving oral PrEP from a clinic that offers LAI PrEP. This survey was conducted in an academic PrEP clinic in the Southeast region, which has the highest rates of new HIV acquisitions and lowest rates of PrEP uptake in the United States [19, 20]. We investigated perceived HIV risk, stigma, PrEP method preference, and concerns about and barriers to PrEP in people who are currently using oral and LAI PrEP or who have previously used PrEP. Overall, the group had low perceived HIV risk and PrEP stigma scores, which is not surprising at a PrEP clinic. Participants generally preferred LAI over oral PrEP; and the most common reasons participants using oral PrEP chose oral over LAI was lack of LAI awareness and/or LAI not being offered to them. We also found the most common general concerns about PrEP among all groups were side effects and costs associated with testing and medication. Collectively, these data suggest that in order to improve slow uptake of LAI PrEP, clinics should focus on improving patient awareness of LAI PrEP and expanding access, as well as improved counseling about side effects.

In this study, the majority of participants who were on LAI PrEP or not currently on PrEP preferred injectable over oral. Participants on LAI overwhelmingly reported that their reasons for choosing LAI over oral included not having to take a pill every day, as well as feeling that LAI was more effective than oral. These findings suggest that convenience factors like not having to manage daily medication and the proven higher efficacy rate [7], in part due to adherence, are benefits for LAI that should be emphasized to patients who are choosing between methods [6]. Furthermore, most participants who were on oral PrEP either preferred injectable or reported having no preference, although those on oral PrEP for more than one year had lower odds of preferring injectable suggesting they were accustomed to oral daily medication. On the other hand, persons on oral PrEP in relationships with one or more persons had greater odds of preferring injectable PrEP, indicating that partner dynamics may have an impact on PrEP modality choice.

Despite a demonstrated appetite for LAI PrEP—both in this study and the rest of the literature [8, 10, 12]—many patients remain unaware and unable to access it [21]. Our data support that participants are not necessarily making active choices to remain on oral, as most participants currently on oral PrEP either were not offered LAI or were not aware of LAI before participating in this study. Additionally, a portion of participants reported that insurance would not cover the medication. Taken together, additional efforts are needed to improve access to LAI PrEP, as patients are interested in this novel modality.

The low perceived HIV risk scores overall may have been influenced by the fact that most participants were taking PrEP to prevent HIV, as participants who were not currently on PrEP had higher risk scores on average than those on either form of PrEP. More than half of the group not on PrEP reported having been sexually active with one or more new partners in the last six months which substantiates the importance of retention efforts for persons who fall out of care. It appears that participants who had previously stopped PrEP were not doing so solely because they were no longer at risk of acquiring HIV. Many participants who stopped PrEP also reported that side effects were a reason for discontinuation. A higher percentage of participants not on PrEP (as opposed to participants currently taking either form) identified as women, non-binary, or trans, populations that have had historically lower uptake of PrEP [20], and they were on average slightly younger. And, despite previous studies showing that higher perceived HIV risk may be associated with preference for LAI PrEP [11], thus influencing our initial hypothesis, our data did not demonstrate that perceived risk was associated with a preference for LAI. Thus, perceived HIV risk may not be the most important factor in patients’ decisions surrounding PrEP.

Stigma has previously been shown to be a large factor in patients’ decisions to start or continue PrEP [8, 11]. This is especially true in the southern United States, where studies have shown intersectionality and HIV-related stigma impact patients’ views of PrEP [22, 23]. In our study, PrEP stigma was uniformly low to moderate across participants, including both those currently on and not on PrEP. This may be indicative that, at least amongst patients willing to participate in surveys and who are engaged in care at an academic PrEP clinic, stigma towards PrEP is not high. Moreover, it could be related to this survey being conducted in a densely populated, urban area. It has been shown that PrEP stigma, and also HIV stigma which is in some ways the root of stigma about PrEP, is generally higher in rural areas [24, 25].

In terms of concerns about PrEP, general concerns were similar between participants currently using PrEP or not on PrEP. Most participants reported side effects as being their top concern, followed by costs associated with medication, clinic visits, and tests. We did not assess whether participants were concerned by prior or possible future side effects, but side effects have persistently been a concern for people considering PrEP, especially those who have been asked about modality preference [15, 26]. To allay concerns about side effects, patients should be given the opportunity to have comprehensive discussions with their providers before beginning medication. Additionally, with newer methods of delivery (i.e., injection causing injection site reactions), special attention should be paid to mitigating side effects in order to improve PrEP retention in care and patient experiences when using PrEP.

This study had some limitations. First, the sample size was modest, especially for participants currently using LAI or not on PrEP. This was particularly limiting to our model of preference for LAI PrEP as the small sample reduced the number of variables we could conceivably control for and there may be potential unmeasured confounders. However, response rate of participants on LAI who were approached for the study was approximately 50%, reflecting the small pool of patients currently on the medication. Second, there was limited diversity in some of the demographic characteristics of the participants, namely most participants were college-educated, privately insured, and identified as gay men. Just three participants reported having no insurance, a large change from previous reports of the demographics in this clinic [4], indicating that participants who were not insured may have been less likely to respond to our survey. While these characteristics may reduce generalizability, the survey participants reflected general trends in demographics of PrEP users [27, 28], and this underlines the necessity of future studies focusing specifically on uninsured people. As an important tool in reducing HIV acquisition, it is essential that research recruitment is focused on groups that have been historically excluded from the healthcare system. Finally, although participants in this study were patients at a clinic which is currently offering LAI PrEP, ability to provide LAI has remained limited due to insurance complications. This may have impacted the extent to which participants on oral PrEP were unaware of or not offered LAI but will be rectified as LAI PrEP becomes more available in the future.

Conclusions

This study is among the first to include participants who are currently using LAI PrEP in a real-life setting. Our results show that length of time on oral PrEP (at least one year) and being partnered (as opposed to single) are associated with preference for LAI PrEP, and that participants have not always been given an active choice between modality due to lack of awareness about, availability of, or simply not being offered LAI PrEP. These findings—taken with participants’ concerns about side effects and cost—indicate that in order to improve uptake of LAI, efforts need to be made to increase accessibility and direct it to people who are most likely to prefer injectables. Future studies and efforts need to be made to make LAI a viable and realistic choice for more patients.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Conceptualization and design: Alice Schaack, Mehri McKellar, Maxwell Allamong, Tina Watkins, and Katherine Link. Survey programming and software management: Maxwell Allamong. Material preparation and data collection: Alice Schaack. Formal analysis and visualization: Frances Hung and Richard Barfield. Writing - original draft: Alice Schaack. Writing - review and editing: all authors.

Funding

Funding for statistical analysis was provided in part by the Duke Center for AIDS Research, an NIH funded program (5P30 AI064518).

Declarations

Conflict of interest

Financial interests: Mehri S. McKellar has previously received funding from Gilead Sciences. All other authors have no financial interests to disclose. Non-financial interests: none.

Ethical Approval

This study was performed in accordance with the 1964 Helinski Declaration and ethical approval was granted by the Duke University Institutional Review Board.

Informed Consent

Informed consent was obtained from all participants.