Awareness about and willingness to use long-acting injectable pre-exposure prophylaxis (LAI-PrEP) among people who use drugs

Abstract

In the Bangkok Tenofovir Study of oral pre-exposure prophylaxis (PrEP; TDF/FTC), adherence was poor. Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) for HIV prevention may help overcome adherence challenges and is currently being tested in clinical trials, but not in people who use drugs (PWUD), an important key population that remains highly vulnerable to HIV. Since PWUD are not currently included in trials of LAI-PrEP, we sought to examine awareness about LAI-PrEP and factors associated with willingness to use LAI-PrEP in this understudied population. Participants included 234 HIV-negative people with opioid use disorder and self-reported HIV–risk behaviors recruited from Connecticut’s largest addiction treatment program. We analyzed data from a standardized assessment using audio computer-assisted self-interview (ACASI) to assess the independent factors associated with willingness to use LAI-PrEP. While only 25.6% of participants were aware of LAI-PrEP (67.1% had heard of oral PrEP), after being given a description of it, 73.5% were willing to use it, if it were available. Participants were most commonly concerned about long-term side effects (76.9%) of LAI-PrEP. Independent correlates of willingness to use LAI-PrEP were female sex (aOR=2.181, p=0.018), recent visit to healthcare provider (aOR=2.9, p=0.023), high perceived risk of acquiring HIV (aOR=3.3, p=0.007), and having previously taken oral PrEP (aOR=3.284, p=0.017). Findings suggest that PWUD are highly interested in PrEP, especially in LAI-PrEP formulations. Our results indicate the potential for LAI-PrEP, as an alternative to oral daily PrEP, to be implemented into existing evidence-based HIV-based HIV prevention efforts that target high-risk PWUD.

1. Introduction

The HIV epidemic among people who use drugs (PWUD) in the U.S. has been declining, but amid a burgeoning opioid epidemic, communities are now increasingly vulnerable to and experiencing HIV outbreaks (Jones, Christensen, & Gladden, 2017; Mack, Jones, & Ballesteros, 2017; Mars, Bourgois, Karandinos, Montero, & Ciccarone, 2014; Peters et al., 2016; Schwetz, Calder, Fauci, Rosenthal, & Kattakuzhy, 2019; Van Handel et al., 2016). Recent HIV outbreaks linked to drug injection have introduced HIV into networks of PWUD and, thus, reversed decades of HIV prevention successes. Pre-exposure prophylaxis (PrEP; TDF/FTC) is one promising approach for preventing HIV infection among at-risk groups and is recommended for high-risk PWUD as part of an integrated HIV prevention package (CDC, 2017; WHO, 2015). PrEP for HIV prevention is especially useful when other evidence-based harm reduction programs for PWUD (e.g., syringe services programs, opioid agonist therapies) are either unavailable or poorly scaled-to-need. Oral PrEP, formulated as a single, daily pill, was first FDA-approved in 2012 following studies documenting its HIV prevention efficacy among key populations (e.g., PWUD, men who have sex with men; MSM) (Baeten et al., 2012; Choopanya, Martin, Suntharasamai, Sangkum, Mock, Leethochawalit, Chiamwongpaet, Kitisin, Natrujirote, Kittimunkong, et al., 2013; Grant et al., 2010; Thigpen et al., 2012; Van Damme et al., 2012). Challenges with oral PrEP persist, including slow uptake and suboptimal adherence and persistence, indicating the need for new delivery mechanisms.

Research is currently evaluating injectable formulations of antiretroviral drugs as candidate agents for use as long-acting injectable PrEP (LAI-PrEP) (Taylor, Tieu, Jones, & Wilkin, 2019). LAI-PrEP is an attractive alternative to oral PrEP (Haberer et al., 2015), especially among individuals for whom daily medication adherence is challenging. LAI-PrEP would be administered to patients as an intramuscular injection in a clinical setting under professional supervision. Although clinical trials remain in progress, early data suggest injections for LAI-PrEP would be spaced at similar time intervals as LAI-ART, which occur approximately every 8 weeks (Delany-Moretlwe & Hosseinipour, 2019; Landovitz, 2020). An appealing alternative, LAI-PrEP may be perceived as a simpler delivery system that can confer a consistent level of protection against HIV, unlike oral PrEP, for which efficacy can modulate greatly based on daily adherence (Harper, 2019; Jackson & McGowan, 2015). LAI-PrEP may also overcome privacy concerns for people who store their medications in discrete locations or by placing them in inconspicuous containers, like vitamin bottles, to avoid stigmatization. It may also provide support for clinicians who lack confidence that PWUD can adhere to daily oral PrEP. Also, LAI-PrEP may be a more convenient option for PWUD patients, given the challenges of adhering to a daily pill-based regimen due to characteristics common among many PWUD, such as chronic substance use and neurocognitive impairment (Huedo-Medina, Shrestha, & Copenhaver, 2016; Shrestha & Copenhaver, 2016; Vik, Cellucci, Jarchow, & Hedt, 2004).

There is a growing literature on the willingness to use oral PrEP (TDF/FTC) in PWUD and MSM (Iniesta et al., 2018; Ojikutu et al., 2019; Patrick et al., 2017; Ransome et al., 2019; Shrestha, Altice, Huedo-Medina, Karki, & Copenhaver, 2017; R. Shrestha et al., 2017). Studies on the preference toward using or willingness to use LAI-PrEP, however, have mostly been focused on MSM (Cheng et al., 2019; Kerrigan et al., 2018; Meyers, Wu, Brill, Sandfort, & Golub, 2018; Meyers, Wu, Qian, et al., 2018). Two qualitative studies in PWUD, however, showed high acceptability and relevance of LAI-PrEP to alleviate many of the barriers PWUD face in taking daily oral PrEP (Allen et al., 2019; Biello et al., 2019; Footer et al., 2019). Quantitative studies examining the preferences for LAI-PrEP in PWUD, however, are lacking. Therefore, we sought to better understand awareness about and willingness to use LAI-PrEP as a potential modality for PrEP delivery in opioid-dependent PWUD. If LAI-PrEP proves to be effective and safe and becomes available in the U.S., understanding preferences for, and attitudes toward, its use among diverse at-risk populations will facilitate rapid scale-up and implementation.

2. Methods

2.1. Participants

We recruited 234 individuals between July 2018 and October 2019. Individuals were eligible if they were: a) 18 years or older; b) self-reported HIV-uninfected or HIV status unknown; c) reported drug- (i.e., sharing of injection equipment) or sex-related (i.e., condomless sex) HIV risk in the past 6 months; d) met DSM-V criteria for opioid use disorder; e) on methadone maintenance treatment; and f) able to understand, speak, and read English. All patients were stabilized on methadone to treat opioid dependence.

2.2. Study setting and procedures

We recruited participants from Connecticut’s largest addiction treatment setting (APT Foundation, Inc.), using clinic-based advertisements and flyers, word-of-mouth, and direct referral from counselors. Trained research assistants conducted all screening, enrollment, and interview activities in a private room. We screened a total of 294 individuals for eligibility, with 234 (79.6%) meeting inclusion criteria. The majority of ineligibility was due to low levels of HIV risk. Following informed consent, all participants completed a 45-minute interview using audio computer-assisted self-interview (ACASI). We reimbursed all participants $25 for their time. The Investigational Review Board (IRB) at the University of Connecticut approved the study protocol, and we received approval from the board of APT Foundation, Inc.

2.3. Measures

We assessed participants for social and demographic characteristics, including age, sex, sexual orientation, ethnicity, marital status, educational status, employment status, annual income, homelessness, visit to a healthcare provider, and current methadone dose. We used standardized scales to assess depression (scores ≥16 indicative of moderate to severe depression on the 20-item Center for Epidemiological Studies Depression Scale [CES-D; Radloff, 1977]); alcohol use disorders (AUD), using the validated 3-item Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) (cut-offs ≥ 4 for men and ≥ 3 for women suggest the presence of an AUD) (Bush, Kivlahan, McDonell, Fihn, & Bradley, 1998); and an HIV risk assessment, adapted from NIDA’s Risk Behavior Assessment (Dowling-Guyer et al., 1994), to measure several aspects of HIV risk behaviors, including measurement of “any” high-risk behavior (sexual or drug-related) in the past 30 days. We measured perceived risk of acquiring HIV by a single question, “What do you think is your current risk of getting HIV?” with a dichotomized response of “low” or “high”. We assessed participants’ satisfaction with previous HIV prevention methods using the question “Are you satisfied with your current method of HIV protection (e.g., condom use, clean needle use, daily oral PrEP use)?” with a dichotomized response of “yes” or “no”.

We assessed participants’ awareness (“Before participating in this survey, have you ever heard of daily oral PrEP for protection against HIV?”) and prior use of daily oral PrEP (“Have you ever used PrEP for protection against HIV?”) after we presented participants with a brief description of daily oral PrEP, administered daily per recommendations for PWUD.

Following these, we asked participants about their awareness about LAI-PrEP (“Before participating in this survey, have you ever heard about the long-acting injectable PrEP for protection against HIV?”). We assessed their interest in LAI-PrEP after providing a brief description of LAI-PrEP. After reviewing the description, we asked participants to respond to a question “Suppose that LAI-PrEP is effective in preventing HIV when injected once every two months. Would you be interested in taking it?” To better understand the pattern of reasoning and decision making around interest in LAI-PrEP use, we explored participants’ perceived concerns related to uptake of LAI-PrEP. We asked participants to indicate their agreement on statements listing concerns related to uptake of LAI-PrEP.

2.4. Data analysis

We performed all data analyses using IBM SPSS v. 25. We computed descriptive statistics, including frequencies and percentages for categorical variables, and means and standard deviations for continuous variables. We conducted bivariate logistic regression analyses between each independent covariate and the dependent variable, willingness to use LAI-PrEP. We then included covariates significant at p<0.10 in a multivariate logistic regression on willingness to use LAI-PrEP. We evaluated estimates for statistical significance based on 95% confidence intervals using p<0.05. We assessed the goodness-of-fit of the final multivariate model using the Hosmer and Lemeshow Test (Hosmer, Hosmer, Le Cessie, & Lemeshow, 1997).

3. Results

3.1. Participant characteristics

Table 1 shows participant characteristics, stratified by their willingness to use LAI-PrEP. Most participants were in their early 40s, with most (74.4%) meeting screening criteria for moderate to severe depression and 31.2% meeting screening criteria for AUD. Almost half of the participants (44.8%) reported injecting illicit drugs in the past 30 days. Of those who reported injecting in the last 30 days, 18.4% reported sharing injection equipment. Of those who reported engaging in sexual activities (e.g., anal, vaginal, or oral) in the past 30 days (71.4%), 39.3% reported having multiple sex partners, and only 6.0% reported always using condoms with their sexual partners. Almost two-thirds of participants (62.0%) reported being satisfied with their current method of HIV prevention (e.g., condom use, clean needle use, PrEP use) and 25.2% perceived that they were at high risk of acquiring HIV.

Table 1:

Characteristics of participants and HIV transmission risk behaviors, stratified by willingness to use LAI-PrEP (Bivariate associations; N=234).

Variables	Entire Sample (N = 234)			Willingness to use LAI-PrEPe		OR f (95% CI g)	p
	Frequency		%	No (n = 62)	Yes (n = 172)
Characteristics of participants
Age: Mean (±SD), years a		42.7 (±10.2)		41.5 (±10.6)	43.1 (±10.0)	1.016 (0.987, 1.046)	0.283
Sex
Male		119	50.9	40 (17.1)	79 (33.8)	-	-
Female		115	49.1	22 (9.4)	93 (39.7)	2.140 (1.174, 3.902)	0.013
Heterosexual sexual orientation
No		49	20.9	12 (5.1)	37 (15.8)	-	-
Yes		185	79.1	50 (21.4)	135 (57.7)	0.876 (0.423, 1.803)	0.721
Ethnicity
Non-White		86	36.8	22 (9.4)	64 (27.4)	-	-
White		148	63.2	40 (17.1)	108 (46.2)	0.928 (0.507, 1.700)	0.809
Currently married/living with partner
No		183	78.2	46 (19.7)	137 (58.5)	-	-
Yes		51	21.8	16 (6.8)	35 (15.0)	0.734 (0.372, 1.449)	0.373
High school graduate
No		65	27.8	16 (6.8)	49 (20.9)	-	-
Yes		169	72.2	46 (19.7)	123 (52.6)	0.873 (0.452, 1.686)	0.686
Employed
No		205	87.6	52 (22.2)	153 (65.4)	-	-
Yes		29	12.4	10 (4.3)	19 (8.1)	0.646 (0.282, 1.478)	0.300
Income level
< $10,000		68	29.1	18 (7.7)	50 (21.4)	-	-
≥ $10,000		166	70.9	44 (18.8)	1 22 (54.1)	0.998 (0.527, 1.892)	0.996
Homelessb
No		103	44.0	26 (11.1)	77 (32.9)	-	-
Yes		131	56.0	36 (15.4)	95 (40.6)	0.891 (0.495, 1.603)	0.700
Visited healthcare providerb
No		27	11.5	12 (5.1)	15 (6.4)	-	-
Yes		207	88.5	50 (21.4)	157 (67.1)	2.512 (1.103, 5.721)	0.028
Methadone Dose (mg): Mean (±SD) a		81.9 (±30.5)		86.9 (±31.2)	80.0 (±30.2)	0.992 (0.983, 1.002)	0.129
Moderate to severe depression
No		60	25.6	16 (6.8)	44 (18.8)	-	-
Yes		174	74.4	46 (19.7)	128 (54.7)	1.012 (0.521, 1.966)	0.972
Alcohol use disorder
No		161	68.8	45 (19.2)	116 (49.6)	-	-
Yes		73	31.2	17 (7.3)	56 (23.9)	1.278 (0.672, 2.430)	0.455
HIV transmission risk behaviors
Duration of drug use: Mean (±SD a) years		18.4 (±10.1)		18.3 (±10.3)	18.4 (±10.1)	1.001 (0.973, 1.031)	0.926
Used illicit drug c
No		74	31.6	22 (9.4)	52 (22.2)	-	-
Yes		160	68.4	40 (17.1)	120 (51.3)	1.269 (0.687, 2.344)	0.446
Injected any illicit drug c	n = 160
No		55	23.5	15 (9.4)	40 (25.0)	-	-
Yes		105	44.9	25 (15.6)	80 (80 (50.0)	1.200 (0.570, 2.526)	0.631
Shared injection equipment c	n = 105
No		62	26.5	15 (14.3)	47 (44.8)	-	-
Yes		43	18.4	10 (9.5)	33 (31.4)	1.053 (0.422, 2.631)	0.912
Engaged in sexual intercourse c
No		67	28.6	18 (7.7)	49 (20.9)	-	-
Yes		167	71.4	44 (18.8)	123 (52.6)	1.027 (0.541, 1.949)	0.935
Multiple sex partner c	n = 167
No		75	32.1	23 (13.8)	52 (31.1)	-	-
Yes		92	39.3	21 (12.6)	71 (42.5)	1.495 (0.749, 2.985)	0.254
Consistent condom use c	n = 167
No		153	65.4	41 (24.6)	112 (67.1)	-	-
Yes		14	6.0	3 (1.8)	11 (6.6)	1.342 (0.356, 5.054)	0.663
Engaged in transactional sex c	n = 167
No		121	51.7	36 (21.6)	85 (50.9)	-	-
Yes		46	19.7	8 (4.8)	38 (22.8)	2.012 (0.854, 4.736)	0.110
Sex under the influence of alcohol c	n = 167
No		94	40.2	29 (17.4)	65 (38.9)	-	-
Yes		73	31.2	15 (9.0)	58 (34.7)	1.725 (0.842, 3.533)	0.136
Perceived risk of HIV transmission
Low		175	74.8	54 (23.1)	121 (51.7)	-	-
High		59	25.2	8 (3.4)	51 (21.8)	2.845 (1.264, 6.404)	0.012
Satisfied with current method of HIV prevention
No		89	38.0	22 (9.4)	67 (28.6)	-	-
Yes		145	62.0	40 (17.1)	105 (44.9)	0.862 (0.471, 1.577)	0.630
PrEP-specific variablesd
Heard of oral PrEP
No		77	32.9	28 (12.0)	49 (20.9)	-	-
Yes		157	67.1	34 (14.5)	123 (52.6)	2.067 (1.135, 3.766)	0.018
Ever used oral PrEP
No		174	32.9	56 (23.9)	118 (50.4)	-	-
Yes		60	25.6	6 (2.6)	54 (23.1)	4.271 (1.734, 10.520)	0.002
Heard of LAI-PrEP e
No		174	74.4	50 (21.4)	124 (53.0)	-	-
Yes		60	25.6	12 (5.1)	48 (20.5)	1.613 (0.791, 3.290)	0.189

Note:

^aSD: standard deviation;

^bin the past 12 months;

^cin the past 30 days;

^dPrEP: pre-exposure prophylaxis;

^eLAI-PrEP: long-acting injectable PrEP;

^fodds ratio;

^gconfidence interval

Among 234 participants (Figure 1), 67.1% and 25.6% of participants reported having heard of oral PrEP and LAI-PrEP, respectively. Similarly, 25.6% had ever used oral PrEP for protection against HIV. Conversations with a healthcare provider (33.3%) and friends (29.9%) were reported as the top sources of PrEP knowledge. The most frequently reported concern about taking LAI-PrEP was the potential for long-term side effects (76.9%). Participants reported slightly less concern about the possibility that the efficacy of LAI-PrEP may wane (37.6%) or confer incomplete protection against HIV (33.3%), followed by the cost of LAI-PrEP (27.4%), fear or dislike of needles (24.8%), and having to return to the clinic for injection of LAI-PrEP every two months (20.5%).

Fig. 1:

PrEP-related variables (N=234).

3.2. Willingness to use long-acting injectable PrEP

More than two-thirds of participants (73.5%) reported that they would be willing to use LAI-PrEP to reduce their risk of HIV infection (Figure 1). While Table 1 shows the results of the bivariate logistic regression of being willing to use LAI-PrEP, Table 2 shows the results of the multivariate logistic regression associated with this outcome. Factors independently correlated with willingness to use LAI-PrEP included female sex (aOR=2.181, p=0.018), being engaged in healthcare (aOR=2.919, p=0.023), having high perceived risk for HIV transmission (aOR=3.255, p=0.007), and having ever used oral PrEP previously (aOR=3.284, p=0.017). We found none of the variables to be co-linear with each other.

Table 2:

Multivariate logistic regression models of factors associated with willingness to use LAI-PrEP (N=234).

Variables		Willingness to use LAI-PrEP c
			aOR c	95% CI d	P
Sex
Male		Ref	-	-
Female		2.181	1.144, 4.159	0.018
Visited healthcare provider (last 12 months) a
No		Ref	-	-
Yes		2.919	1.156, 7.370	0.023
Perceived risk of HIV transmission
Low		Ref	-	-
High		3.255	1.372, 7.721	0.007
Heard of oral PrEPb
No		Ref	-	-
Yes		1.202	0.618, 2.340	0.588
Ever used oral PrEP
No		Ref	-	-
Yes		3.284	1.242, 8.684	0.017
	R2 = 0.180
	Hosmer and Lemeshow Test: Chi-square = 3.079; p = 0.929

Note:

^ain the past 12 months;

^bPrEP: pre-exposure prophylaxis;

^cLAI-PrEP: long-acting injectable PrEP;

^daOR: adjusted odds ratio;

^eCI: confidence interval

4. Discussion

To our knowledge, this is the first quantitative survey study to evaluate the willingness to use LAI-PrEP for HIV prevention among PWUD. As the opioid crisis in the U.S. expands and HIV transmission outbreaks continue, the demand for PrEP in PWUD will likely increase. Clinicians, however, have not enthusiastically prescribed PrEP to PWUD, partially due to concerns of low adherence (Calabrese et al., 2019; Shrestha, Altice, Karki, & Copenhaver, 2017; Spector, Remien, & Tross, 2015). Findings here suggest that there is suboptimal awareness of oral PrEP and very low awareness of LAI-PrEP among PWUD. Future studies should further evaluate the acceptability of LAI-PrEP in PWUD, including scale-up in the U.S., if available (K. Biello et al., 2018; Choopanya, Martin, Suntharasamai, Sangkum, Mock, Leethochawalit, Chiamwongpaet, Kitisin, Natrujirote, & Kittimunkong, 2013).

Despite that all participants in this sample reported injection and/or sexual risk behaviors, nearly two-thirds (62%) reported being satisfied with their current HIV prevention strategy. Considerable data point to this disconnect between risk-taking and perception (Khawcharoenporn et al., 2019; MacKellar et al., 2005; MacKellar et al., 2007; Maughan-Brown & Venkataramani, 2017; Seekaew et al., 2019). After learning more about LAI-PrEP, a large proportion of PWUD were willing to use it, although they expressed concerns about its efficacy, safety, and cost. This is consistent with findings from qualitative interviews with PWUD in other settings, in which participants reported LAI-PrEP to have numerous adherence and logistical advantages over oral PrEP, which must be taken daily (Allen et al., 2019; Biello et al., 2019; Footer et al., 2019).

Not surprisingly, we found that those who had previously used oral PrEP were more likely to be willing to use LAI-PrEP; however, the awareness about PrEP, irrespective of the route, was not associated with the willingness to use LAI-PrEP. This may reflect that PWUD who have taken oral PrEP previously are generally satisfied with the concept of PrEP, or it could indicate that this group had wanted PrEP, but were dissatisfied with it as an oral formulation. This difference also supports findings from qualitative research that found PWUD perceived LAI-PrEP as being easier to adhere to relative to oral PrEP (Allen et al., 2019; Biello et al., 2019; Footer et al., 2019). Other factors explored in other studies suggest that multilevel barriers to PrEP utilization in PWUD exist, including competing health priorities, stigma, and discrimination by healthcare providers who deem them unsuitable for PrEP and among other PWUD in their social network who perceive them as irresponsible and taking too many risks. Other barriers to PrEP utilization include suboptimal capacity for PrEP delivery for PWUD and interrupted care related to homelessness, transportation difficulties, and criminal justice involvement (K. B. Biello et al., 2018; Shrestha & Copenhaver, 2018). Therefore, the availability of LAI-PrEP may be an attractive alternative for those interested in PrEP and may provide a new option for HIV prevention.

It is important to note that female participants were significantly more willing to use LAI-PrEP than males. Females may have perceived injectable formulation, unlike an oral regimen, to provide sustained protection from HIV independent of individual behavior (e.g., daily pill-taking). From a biomedical perspective, this could be a game-changer because females must adhere to much higher levels of PrEP relative to males due to a higher adherence threshold of oral PrEP among females (Cottrell et al., 2016; Hendrix et al., 2016; Louissaint et al., 2013; Patterson et al., 2011). Though it merits further exploration, evidence from the contraceptive literature shows several parallels with females’ interest in LAI-PrEP. First, females have used long-acting contraception in a variety of formulations for decades, including oral, injectable, and patch. Second, women may find LAI-PrEP more appealing, as it may reduce the stigma that one has multiple sex partners because she takes oral PrEP medications. Previous studies have shown that women who have experienced intimate partner violence, which is frequently reported among female PWUD (Meyer, Springer, & Altice, 2011), are more fearful of taking medications due to partner resistance (Braksmajer, Senn, & McMahon, 2016). Qualitative findings have suggested several pathways through which partner violence may cause short-term lapses in contraception adherence, including stress, being forced to leave the home, or a partner who steals pills (Roberts et al., 2016). LAI-PrEP may be able to help women to overcome many of the challenges of using oral PrEP, and to improve the PrEP care continuum for women who use drugs—a marginalized, at-risk, and understudied group.

Future research should investigate whether those who are already engaged in healthcare are more likely to prefer LAI-PrEP. There is a longs history of mistrust between PWUD and clinicians (Altice, Mostashari, & Friedland, 2001; Ostertag, Wright, Broadhead, & Altice, 2006), and it may be that those who engage in healthcare are most accepting of biomedical prevention, including new options. Notably, we recruited participants in the current study from an addiction treatment program, in which healthcare providers saw the participants regularly for their opioid use disorder. While participants in this study reported a high level of engagement with providers, mostly counselors, future research must focus on how clinicians can create an environment in which potential PrEP users can engage in dialogue with the clinicians. This includes communication around whether LAI-PrEP or oral PrEP is right for them in a given moment, particularly given the potential for healthcare-related stigma and discrimination, as well as medical mistrust that impedes access and uptake (K. Biello et al., 2018; K. B. Biello et al., 2018; Shrestha & Copenhaver, 2018). Although most participants in our study did not feel that attending LAI-PrEP appointments every two months would be a challenge, a clinician must navigate some concerns related to LAI-PrEP use (e.g., potential side effects and efficacy) during visits. As a cautionary note, studies of other long-acting treatments for alcohol or opioid use disorder show that PWUD often discontinue treatment after three months (I. Makarenko et al., 2019; J. Makarenko et al., 2017; Springer, Brown, Di Paola, & Altice, 2015).

It is important to note that individuals who stood to benefit the most from PrEP (i.e., those who perceived themselves to be at high risk for HIV acquisition) tended to be the most willing to use LAI-PrEP. This is consistent with prior studies among MSM (Cheng et al., 2019; Meyers, Wu, Qian, et al., 2018) as well as for oral PrEP (Roman Shrestha, Pramila Karki, et al., 2017). Our results suggest that participants are making a rational judgment about their risk levels when considering whether to use PrEP. This may indicate not only a concern about the risk of HIV infection but also a self-management response to their HIV risk behaviors, especially given that almost 40% of our sample reported not being satisfied with their current method(s) of HIV prevention. More research is needed, however, to better understand this finding, to understand participants’ perceived and actual HIV risk, and to understand the implications of appropriate PrEP messaging in this subgroup of PWUD.

When interpreting our findings, readers should consider certain limitations. Our study relied on cross-sectional data, restricting our ability to infer the causal directions underlying the observed associations. The use of self-reported measures may have resulted in participant underreporting of socially undesirable behaviors (e.g., sexual or drug-related risk behaviors) or inconsistent reporting (e.g., mental health) because of stigma or fear of judgment. However, this is unlikely given the high risks that this sample reported and our use of ACASI for data collection. Additionally, we screened the PWUD in this study specifically for substantial risk and all were enrolled in methadone maintenance; therefore, our findings may not be generalizable to PWUD in other settings. Notwithstanding these limitations, our results indicate high acceptability and potential relevance of LAI-PrEP as an alternative to oral daily PrEP for existing evidence-based HIV-based HIV prevention efforts that target high-risk PWUD.

5. Conclusion

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) may be an alternative to the oral form of PrEP currently prescribed to individuals at high-risk for HIV infection. PWUD are an important target population for HIV prevention and could greatly benefit from LAI-PrEP. If LAI-PrEP were found to be efficacious and it were provided for free, it could circumvent uptake and adherence challenges associated with daily oral PrEP, thereby reducing social disparities in HIV transmission in this underserved group. Unfortunately, the ongoing clinical trials to test the efficacy of LAI-PrEP do not target PWUD. The exclusion of this at-risk group from LAI-PrEP-related research and programmatic efforts represents a missed opportunity and indicates a vital avenue for future research.

Highlights.

• Long-acting injectable PrEP (LAI-PrEP) is currently being studied as an alternative form of oral PrEP for HIV prevention.

• We examined the awareness and willingness to use LAI-PrEP among people who use drugs (PWUD).

• While only 25.6% of participants were aware of LAI-PrEP, 73.5% were willing to use it, if made available.

• Findings indicate the potential relevance of LAI-PrEP as an alternative to oral daily PrEP for HIV prevention in PWUD.