A missing perspective: injectable pre-exposure prophylaxis for people who inject drugs

Abstract

The efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention has been established among people who inject drugs (PWID). HIV uninfected, at risk PWID, could likely benefit from long acting injectable formulations of PrEP (“LAI-PrEP”); however, its acceptability in this population has not been previously documented. Thirty-three HIV-uninfected PWID in the U.S. Northeast completed an in-depth interview regarding perceived acceptability of LAI-PrEP. Coded data were synthesized using deductive thematic analysis. The majority of PWID interviewed believed LAI-PrEP would be acceptable. Participants perceived that receiving injections every two months would reduce barriers to daily oral PrEP adherence, including forgetting while “high” and safeguarding pills when homeless. A few participants expressed concerns regarding LAI-PrEP, including medical mistrust, a concern that injections could alter their “high” or be “triggering” for PWID. LAI-PrEP has the potential to reduce HIV among PWID; however, their perspectives are largely absent from research examining its efficacy, representing a missed opportunity.

Background

Antiretroviral pre-exposure prophylaxis (PrEP) is CDC-recommended for HIV prevention among at-risk people who inject drugs (PWID) (Centers for Disease Control and Prevention, 2017), a group disproportionately affected by HIV/AIDS in the United States (U.S.) (Lansky et al., 2014) and in many countries globally (Mathers et al., 2010). While the expansion of syringe service programs (SSPs) has dramatically reduced rates of HIV transmission via injection drug use over the past decade (MacArthur et al., 2014), SSP access is insufficient (amfAR, 2017; Burnett, Broz, Spiller, Wejnert, & Paz-Bailey, 2018) and injection and sexual risk behaviors remain common in this population (Burnett et al., 2018). Moreover, recent outbreaks of HIV due to injection drug use (Conrad et al., 2015) suggest that new interventions, possibly involving PrEP, warrant exploration.

Currently, the only U.S. FDA-approved formulation of PrEP is a daily oral pill. When taken as prescribed, PrEP decreases a risk of HIV infection by over 90% (CDC, 2017; US Public Health Service, 2014). However, in the only clinical trial to test PrEP among PWID to date, the Bangkok Tenofovir Study (Choopanya et al., 2013), adherence to daily PrEP was suboptimal (Choopanya et al., 2013), particularly among men, younger participants, and those with recent incarceration and methamphetamine use (Martin et al., 2015). While over 60% of eligible individuals chose to continue taking PrEP for the open-label extension of the Bangkok Tenofovir Study, more than a quarter of participants did not return for any follow up visits and three quarters self reported less than 90% adherence (Martin et al., 2017). Outside of this setting, very little is known about PrEP uptake and adherence among PWID (Escudero, Lurie, Kerr, Howe, & Marshall, 2014; Koechlin et al., 2017).

Our team conducted a qualitative study to assess interest in and barriers to PrEP use among PWID in two cites in the Northeastern United States, a region where injection drug use is widespread (Cicero, Ellis, Surratt, & Kurtz, 2014; Massachusetts Department of Public Health, 2014) and has been linked to recent HIV and HCV transmission (Massachusetts Department of Public Health, 2017). We found that PrEP knowledge was low and interest in PrEP was mixed and depended in large part on perceived HIV risk (Bazzi et al., 2018). Although perspectives on adherence to daily oral PrEP regimens were mixed, many participants felt that taking a pill daily would be feasible. However, both PWID and key informant health and social service providers who participated in the study described multilevel barriers to PrEP utilization, including concerns about side effects, competing priorities due to drug use, stigma regarding drug use from healthcare providers and within participants’ networks, a lack of capacity for PrEP delivery and issues related to homelessness, transportation, and criminal justice involvement (Biello, Bazzi, et al., 2018).

In order to minimize potential adherence barriers associated with taking daily oral PrEP, particularly for getting due to competing priorities and stigma associated with being seen taking an HIV-related pill, new PrEP modalities are being developed and tested. Specifically, with the safety and acceptability of Cabotegravir for long-acting injectable PrEP (LAI-PREP) now established (Hosek et al., 2017; Markowitz et al., 2017), large-scale clinical trials are underway to test its efficacy when given once every two months among at-risk cisgender men and transgender women who have sex with men (i.e., HPTN 083) (Landovitz & Grinsztejn, 2016) and at-risk cisgender women (i.e., HPTN 084) (Delany-Moretlwe & Hosseinipour, 2017). Unfortunately, these studies do not target PWID, a group with persistent HIV risk that could likely benefit from long-acting formulations of PrEP. If LAI-PREP proves to be effective and becomes available in the U.S., understanding preferences for, and barriers and facilitators to its use among diverse at-risk populations will facilitate implementation. However, to our knowledge, no studies to date have examined the acceptability, interest or perceived advantages and disadvantages of LAI-PREP among PWID.

Methods

Study design and sample

As described previously (Bazzi et al., 2018; Biello, Bazzi, et al., 2018), we conducted a qualitative study to assess awareness, acceptability, interest, barriers and facilitators to PrEP use among high-risk PWID in Boston, Massachusetts, and Providence, Rhode Island. In brief, to recruit high-risk PWID, we partnered with four community-based organizations (CBOs) including SSPs and drop-in HIV/HCV testing centers, and enrolled men and women ≥18 years of age who were HIV-uninfected (self-report) and reported injecting any drugs in the past-month. Purposive sampling helped maximize diversity in participants’ demographics (age, sex) and risk behaviors (receptive syringe sharing, condomless sex). Eligible PWID (hereafter, “participants”) provided verbal informed consent. The Boston University Medical Center institutional review board approved the study, and all participants completed an informed consent process.

Data collection

From October 2016–October 2017, trained qualitative interviewers conducted confidential interviews in private offices or other spaces within CBOs. Interviewers administered brief demographic and behavioral questionnaires and then used field-tested semi-structured interview guides to explore LAI-PREP acceptability, interest and perceptions about use. Interviewers briefly introduced LAI-PREP using the following description:

There is also a new form of PrEP under development that can be injected every 8 weeks. This is long-acting form of PrEP that does not require taking a pill every day, but it does require appointments with a provider for clinical screening and monitoring.

Detailed probes then explored perceived advantages and disadvantages to LAI-PREP utilization. Interviews were audio-recorded and professionally transcribed for text analysis. Participants received $25 for participating in the study.

Data analysis

We reviewed transcripts for quality and to identify emergent themes (Kvale & Brinkman, 2009). As previously described (Bazzi et al., 2018; Biello, Bazzi, et al., 2018), we employed a collaborative codebook development pro-cess (DeCuir-Gunby, Marshall, & McCulloch, 2011; MacQueen, McLellan, Kay, & Milstein, 1998) involving six research team members. Through multiple rounds of codebook development and refinement, we finalized the codes and then three analysts used NVivo (v11) to apply final codes to transcripts. More in-depth thematic analysis then involved synthesizing coded data to identify and clarify key themes regarding perceived acceptability, advantages and disadvantages to using LAI-PREP, as well as differences in interest for LAI-PREP compared to oral daily PrEP. Findings are provided in the sections below using illustrative quotes.

Results

See Table 1 for characteristics of 33 participants.

Table 1.

Sample characteristics (N = 33).

	n (%)
Age in Years; Median (Interquartile Range; IQR)	36 (31.5–48)
Racea
Black or African American	8 (21%)
White	21 (67%)
Other	6 (18%)
Ethnicity: Hispanic/Latinx	8 (24%)
Gender
Male	18 (55%)
Female	13 (39%)
Transgender or Genderqueer	2 (6%)
Education Attainment
Less than High School	9 (27%)
High School or GED	13 (39%)
Some College	11 (33%)
Sexual Orientation
Heterosexual or “Straight”	21 (64%)
Bisexual	8 (24%)
Homosexual or Gay	4 (12%)
Sexual Health and Behaviors
HIV testing, past year
0	2 (6%)
1–2	18 (56%)
3+	12 (37%)
Has Ever Been Diagnosed with Hepatitis C	26 (79%)
How Many Years Have You Been Diagnosed with Hepatitis C;	5 (1.5–9)
Median (IQR)
Number of Sex Partners, Past 3 Months
0	6 (18%)
1	12 (36%)
2+	15 (45%)
Condom Use with Vaginal or Anal Sex, Past 3 Months	11 (33%)
Never	11 (33%)
Rarely/Sometimes/Usually	5 (15%)
Always	6 (18%)
No Vaginal or Anal Sex
Substance Use Behaviors
Frequency of Injection Drug Use, Past 3 Months
Once a Week or Less	5 (15%)
2–6 Days a Week	8 (24%)
1+ Times per Day	20 (60%)
Receptive Syringe Sharing - Number of People, Past Month
0	14 (42%)
1 −2	13 (39%)
3+	6 (18%)
PrEP Knowledge
Had Heard of Oral PrEP Prior to Study Participation	12 (36%)

^aPercentages may exceed 100% because some participants may have multiple responses.

Notably, only 12 participants had heard about oral PrEP prior to the beginning of the study. After hearing the description of LAI-PREP, most participants were enthusiastic about it and expressed greater interest in LAI-PREP than daily oral PrEP:

B04: I think that [LAI-PREP] would be awesome. That would be … really cool. If that would come out, I would do that, right now.

(Boston, cisgender woman)

A primary reason for preferring LAI-PREP over daily oral PrEP related to easier adherence:

P06: The injection would be much better because [it] would prevent people from having to come and take the pill, and this and that, and then forgetting to take the pill … I’m sure a person would remember to come back in about eight weeks for some kind of injection, yeah.

(Providence, transgender woman)

P16: I think that’s pretty cool. I mean, you don’t have to worry about taking it every day, like, say you use someone’s needle and they could have HIV and you forget to take your pill … You know, [for] people that [are] very forgetful, it would be great.

(Providence, cisgender man)

Related to the challenges of daily adherence, several participants perceived particular benefits of LAI-PREP during drug “binges” or periods of frequent use:

P11: I think it’d be a lot better … You don’t have to constantly do it every day, every day, every day … ‘Cause a lot of times, I’ll be high two, three days, you know, and I could miss it those days … And not even be at home where my pills are at. I could be at somebody else’s house … getting wasted. So if it was something like that, like a shot every eight weeks, that’d be like, “Wow, cool.” I wouldn’t have to worry about it every day, you know, that’s one less stress.

(Providence, cisgender man)

For homeless or marginally-housed PWID, participants discussed the benefits of not needing to carry or store medications:

B16: Plus you don’t have to worry about it being stolen or losing it or whatever. For an addict [that] would be helpful because that’s just one less thing that we have to concern ourselves about.

(Boston, cisgender woman)

Most participants perceived that getting an injection every 2 months would not be a major barrier. They expressed that follow-up clinical care would be easier to manage because they would value getting their injections, would be able to keep scheduled appointments, and could get their PrEP-related bloodwork done during the same visit:

P02: That’s really reasonable, every eight weeks. Less worries on “How am I gonna get to the doctor?” or “How am I gonna get bloodwork done, or other tests?” So see them then, get injected or get the shot, and go on and not worry about it for a couple months. That’s awesome. That’s better than taking something every day.

(Providence, cisgender woman)

One female participant also compared the convenience of LAI-PREP to injectable and implantable contraceptives:

B04: I would much rather just come get a shot every eight weeks than have to like take a pill every day. I got [an intrauterine device] because I could not for life of me remember to take birth control every day.

(Boston, cisgender woman)

While most participants had positive reactions to LAI-PREP, some felt that they would need more information about it, including who might give the injections, what the side effects would be, and what the costs would be compared to oral PrEP. Some of these concerns related to general mistrust of medical systems and providers and apprehension about being injected with unknown substances:

P17: The pill would go through my stomach and what not, but I don’t want nothing going in my blood stream … I mean, I want to live, period and point blank … I don’t want to be another statistic, like another guinea pig, you know, like “Oh, it didn’t work on him.”

(Providence, cisgender man)

P14: Oh, no, no, no, no, no. The only one that sticks me with needles is me and my tattoo artist. [LAUGH] Oh no, I’ll stick with the pill … I don’t know if the government’s going to have some kind of way to stick a fucking needle in me and have a little thing in me, know me at all times. That’s why I don’t like going to hospitals that much.

(Providence, cisgender man)

While some participants did not express concerns about the actual injection of LAI-PREP (e.g., “being a heroin addict who uses needles, I’m not afraid of needles”), one participant worried that being injected could be very triggering for PWID trying to enter recovery:

B12: I’m trying to ween myself away from the needle, period … [LAI-PREP] is still a needle, still a bad trigger … Okay, I’ll give you an example. Say you’re drawing up blood, and I happen to walk by and see you as you’re doing it, and my stomach rumbles. I want to get high now. I want to shoot up because I seen it like that. Now I want to put something in the needle and put it in my arm so I can get that feeling again. It’s very triggering.

(Boston, cisgender man)

Additionally, some participants worried about the possibility that LAI-PREP could “affect their high” or block the effects of drugs like extended-release, injectable opioid antagonists:

B01: But if it affects your high and stuff, its not gonna happen, because people don’t like to have that, “Oh I do this and then I’m screwed for eight weeks,” you know what I’m saying?

(Boston, cisgender man)

Finally, although most participants believed that LAI-PREP would be easier to use than daily oral PrEP due to the lack of daily adherence challenges, some worried about attending appointments every two months for injections. A few participants suggested strategies that could help PWID access LAI-PREP consistently, including appointment reminder calls for their bi-monthly scheduled visits, as well as distributing LAI-PREP at local pharmacies (“like a flu shot”) rather requiring patients to see providers or specialists in clinics or hospitals.

Discussion

PWID remain at high risk of HIV/AIDS in the United States due to injectionand sexual-related risk. While PrEP has demonstrated efficacy in reducing HIV transmission among PWID, uptake has been limited in this population. In the only PrEP clinical trial to include PWID to date, adherence among PWID was suboptimal (Choopanya et al., 2013). In our qualitative study of perceived challenges to PrEP uptake and adherence among PWID in the U.S. Northeast, we found that PrEP knowledge was low (Bazzi et al., 2018). While many felt that taking a pill daily would be feasible, multilevel, complex barriers to adherence were described, including forgetting due to competing priorities, stigma and homelessness (Biello, Bazzi, et al., 2018). As such, PrEP modalities that do not require daily adherence, including long-acting injectable formulations, may be an extremely beneficial HIV prevention technology for PWID. If LAIPREP proves to be effective and becomes available in the United States, understanding preferences for, and barriers and facilitators to its use among high-risk populations will facilitate implementation.

In this study, we found LAI-PREP to be acceptable among PWID, with many participants perceiving numerous adherence and logistical advantages over daily oral PrEP medications, including not having to remember to take a daily pill during drug binges and not having concerns about safe storage while homeless or on the street. Our findings are consistent with research on preferences for LAI-PREP among other populations. Qualitative data from users of LAI-PREP in the Phase II safety trial demonstrated that almost all participants reported being interested in continuing with LAI-PREP, versus a daily pill, due to its convenience and lack of adherence demands (Kerrigan et al., 2017). Similarly, in studies of U.S. men who have sex with men (MSM), participants indicated a preference for LAI-PREP over oral PrEP (John, Whitfield, Rendina, Parsons, & Grov, 2018) and noted advantages over daily regimens for those with adherence difficulties and riskier sexual behaviors (Biello et al., 2018; Biello, Mimiaga, Santostefano, Novak, & Mayer, 2018; Parsons, Rendina, Whitfield, & Grov, 2016). For PWID, who may have even more difficulty with daily adherence (Biello, Bazzi, et al., 2018; Choopanya et al., 2013; Martin et al., 2017) due to competing priorities and structural barriers, LAI-PREP may be even more beneficial.

While LAI-PREP removes important challenges related to taking and safeguarding medications, individuals would still need to receive injections every 2 months, which could represent an important challenge for this population. Although most participants in our study did not feel that attending LAI-PREP appointments every eight weeks would be difficult, studies have shown that access to and retention in medical care is challenging for PWID (Hall et al., 2012; Rebeiro et al., 2013), who often feel stigmatized (Biancarelli et al., In Press; Paquette, Syvertsen, & Pollini, 2018) and have high levels of medical mistrust (De Molina et al., 2002; van Boekel, Brouwers, van Weeghel, & Garretsen, 2013). In order to reduce loss to follow up and minimize missed doses, innovative intervention strategies will be needed. For example, a patient navigator (Bradford, Coleman, & Cunningham, 2007) or community health worker (Morgan, Lee, & Sebar, 2015) model could be used to ensure more frequent and ongoing contact with patients and facilitate their attendance at bimonthly appointments. Moreover, these community health workers could help navigate issues around insurance and applying for medication assistance programs to cover the costs.

Consideration of alternative PrEP delivery models is warranted. One promising strategy could involve providing PrEP care and injections at SSPs or other CBOs or pharmacies where PWID go frequently (often daily or at least weekly) for other products and services (e.g., syringes, HIV/STI/HCV testing, case management). PWID often having ongoing relationships with trusted staff at these organizations that should be considered in the development of targeted PrEP delivery interventions for this population. In areas where harm reduction services do not exist or are not as easily accessible, PrEP could be delivered through walk-in clinics or urgent care centers where PWID go for other medical services (e.g., wound care).

These findings are not without limitations. First, participants were PWID in two urban centers in the U.S. Northeast, where access to public health services is high compared to other regions or more rural areas where services may be much more limited. Additionally, by partnering with CBOs for recruitment, we may have missed PWID who are completely disconnected from harm reductions services, and these individuals may differ in their preference for LAI-PrEP. However, we implemented purposive sampling to recruit higher risk individuals (e.g., those reporting recent syringe sharing and condomless sex). In order to expand generalizability, future studies should seek to include PWID from more rural areas, with less connection to services, and in other regions and countries where drug use and risk behavior profiles likely differ. Lastly, our participants had no direct experience using LAI-PREP and could only discuss hypothetical preferences and barriers.

Notwithstanding these limitations, the findings of the current study suggest high acceptability and relevance of LAI-PREP among PWID, a marginalized, at-risk, and often understudied population. Unfortunately, little research on LAI-PREP explicitly includes PWID. In fact, two large-scale clinical trials testing the efficacy of LAI-PREP with Cabotegravir (HPTN 083 and 084) likely exclude most PWID due to restrictive eligibility criteria (e.g., no alcohol or substance use “that, in the opinion of the study investigator, would interfere with the conduct of the study;” Hepatitis C virus antibody negative) (Delany-Moretlwe & Hosseinipour, 2017; Landovitz & Grinsztejn, 2016). Given the high level of HIV risk experienced by PWID globally, exclusion of this population from PrEP-related research and programmatic efforts represents a major missed opportunity and a vital avenue for further research.