A Scoping Review of HIV Pre-exposure Prophylaxis Stigma and Implications for Stigma-Reduction Interventions for Men and Transwomen Who Have Sex with Men

Abstract

HIV remains a public health concern in the United States. Although pre-exposure prophylaxis (PrEP) can be expected to reduce HIV incidence, its uptake, adherence, and persistence remain limited, particularly among highest priority groups such as men who have sex with men and transwomen (MSMTW). Using a socioecological framework, we conducted a scoping review to examine PrEP-related stigma to inform future research, policy, and programmatic planning. Using the PRISMA extension for scoping reviews, we conducted database searches from August 2018 to April 2020 for articles addressing PrEP stigma. Studies were independently screened and coded by three authors, resulting in thematic categorization of several types of PrEP stigma on four socioecological levels. Of 557 references, a final sample of 23 studies was coded, 61% qualitative, and 87% focusing exclusively on MSMTW. Most instances of PrEP-related stigma occurred on the interpersonal level and included associations of PrEP with risk promotion, HIV-related stigma, and promiscuity. Other frequent themes across socioecological levels included provider distrust and discrimination, government and pharmaceutical industry distrust, internalized homonegativity, PrEP efficacy distrust, and anticipated homonegativity. Notably, PrEP was also framed positively as having physical and psychological benefits, and assuming responsibility for protecting one’s community via PrEP awareness-raising. PrEP-related stigma persists, demanding interventions to modify its impact. Leveraging PrEP-positive discourses to challenge PrEP stigma is an emerging avenue, alongside efforts to increase provider willingness to promote PrEP routinely by reducing provider bias, aligning with the national strategy to End the HIV Epidemic.

Introduction

HIV remains a major public health priority in the United States (U.S.), where 37,968 new HIV cases have recently been reported [1]. Reductions in HIV incidence plateaued in 2013 and have remained stable overall since, primarily because multiple barriers to HIV prevention and treatment for high-risk groups remain [1–5]. Notably, incidence has continued to increase in some groups, particularly among persons aged 25–34, and Black and Latinx men and transwomen who have sex with men (MSMTW) [6]. As such, the HIV epidemic continues to disproportionately affect the U.S. racial minority MSMTW population [7]. With a 50% lifetime risk of HIV and an incidence 23 times that of White heterosexual men [8], Black MSM are at staggering risk of acquiring HIV. The U.S. national HIV strategy and End the HIV Epidemic initiatives both recognize these disparities and aim to address them to reduce HIV incidence [7, 9].

Expansion of antiretroviral therapy use, which prevents forward transmission of HIV once viral suppression is reached and sustained, can be expected to contribute to further incidence reductions [10], if rates of viral suppression increase uniformly across various priority populations (e.g., MSM, transgender individuals). In addition, Pre-Exposure Prophylaxis (PrEP), currently approved in the U.S. as a once-daily fixed dose of emtricitabine and tenofovir, is 99% effective in preventing HIV acquisition when taken as prescribed [11]. Yet, uptake, adherence and persistence of PrEP have been limited [12–14], particularly in the populations at highest risk for HIV acquisition, such as young MSMTW of color [15–18].

Stigma affects quality of life and healthcare engagement for MSMTW, especially for MSMTW of color, and contributes to poorer HIV-related outcomes for HIV-positive individuals [19]. High levels of stigma also contribute to the increased HIV vulnerability of MSMTW of color given that they experience intersecting stigmas of race, ethnicity, sexuality, HIV, and, most recently, PrEP-related stigma [20]. Evidence shows that stigma occurring on multiple levels affects HIV prevention methods such as PrEP by impeding awareness, uptake, adherence and persistence [21]. Furthermore, discrimination against members of the Lesbian, Gay, Bisexual, Trans, and Queer (LGBTQ) community impede healthcare and HIV prevention engagement [22, 23]. Among transgender individuals, gender identity disclosure is a significant barrier, and often tied to fear of discrimination and stigma [23, 24]. For Black MSM and transwomen, individual and systemic racism significantly impact HIV healthcare engagement and outcomes [25–27].

Further, there is considerable PrEP-related stigma from within the MSMTW community, often shaping motivations for PrEP uptake [28–31]. For example, shaming of PrEP users [28] through assumptions of sexual promiscuity [32, 33] and risk taking [33–35], as well as fears of being perceived as HIV-positive [36], have posed major barriers to its use. Notably, another group that is at increased risk for poor HIV-related outcomes, primarily driven by stigma, are transgender men (transmen) [37]. However, the research to date on transmen and PrEP evidences a considerable gap, demanding significant future efforts in this direction. It therefore follows from the above that finding mechanisms to reduce PrEP-associated stigma, across diverse priority groups, is essential [20]. A first step would be to rigorously document the types and characteristics of the stigma that surround PrEP use, in order to directly target them.

There is an increasing body of literature addressing stigma related to PrEP use with varying foci (e.g., it being a primary or exploratory study outcome), addressing a wide range of topics (e.g., disclosure of use, access, relationship implications), and using different measures of assessment (e.g., in-depth interviews, focus groups or surveys). Yet, consensus within this literature has not been reached in terms of how to comprehensively frame and evaluate various types of stigma, with the goal of informing interventions to reduce stigma-related barriers impacting PrEP utilization [33, 38–45].

Prior studies have framed stigma dimensions based on how these are manifested and/or experienced by their targets, categorizing stigma into experienced, perceived, anticipated, and internalized stigma [46]. Experienced stigma is often conflated or combined with enacted stigma, and can include acts of discrimination and shaming, or refer to lived experiences of stereotypes, prejudice, rejection, or violence [31, 47]. Perceived stigma reflects a person’s perception of the sociocultural climate including perceptions of homonegativity, while anticipated stigma refers to the expectation of rejection [31, 48]. Additionally, there is also conflation of perceived and anticipated stigma. For example, Brooks et al. [31] included perceived stigma in their anticipated stigma framing, whereas other authors provide a clearer distinction between the two [33, 49]. Internalized stigma refers to negative self-evaluation as a reflection of ubiquitous stigma in one’s environment, which an individual has attributed to themselves, leading to a negative self-view or self-appraisal [46]. Recently an additional stigma-related dimension has emerged, namely challenging stigma, which explicitly references acts of stigma mitigation and is based on resilience and coping [38, 50–54]. In addition to types of stigma that act on individual, interpersonal, community, and institutional levels, structural stigma refers to the climate of laws, policies and processes that create and/or perpetuate stigma [55].

Importantly, there are different forms of stigma an individual may experience that are attached to different attributes, such as socioeconomic status, mental health conditions, and often being of a minority status. Racial and ethnic minority MSMTW may experience stigma related to their sexual minority identity, race, and HIV status, whether actual or presumed [19]—a phenomenon often referred to as intersectional stigma, when multiple stigmas combine in a multiplicative, rather than additive, manner [56]. Intersectionality focuses on the experience of people from multiply marginalized groups and acknowledges that these multiple social identities produce disparate health outcomes via a confluence of negative social forces such as racism, sexism, transphobia, homophobia and HIV stigma [57].

An organizing framework that may readily lead to understanding the types of interventions needed to combat PrEP-related stigma is the socioecological model [58, 59], which has been widely used across fields, including within HIV research [60]. This approach accounts for the layers of influence that impact health behavior, with the most proximal one being the individual level (one’s own cognitions, affect and behavior), and the most distal being the structural level (laws and policies at a national level). Several published papers on stigma related to PrEP have applied the socioecological model to demonstrate how PrEP stigma operates on various levels of this system [38, 55, 61]. The current scoping review examines the occurrence of PrEP-related stigma on four levels of the socioecological model. At the individual level, for example, internalized homonegativity may lead to increased vulnerability to HIV transmission [62, 63], potential distrust in PrEP efficacy, or side effect concerns that limit PrEP uptake among MSMTW [64]. At the interpersonal level, stigma manifests as shaming individuals with multiple sex partners [45, 65], or suspecting one to be HIV positive [5, 66]. At the community level, homonegativity or shaming from outside or within the LGBTQ community are manifestations of stigma [21, 29, 49, 67]. Recurring experiences of discrimination and unfair treatment by individual healthcare providers and clinic environments lead to medical distrust by patients faced with such negative endemic encounters [68]. Distrust in providers [21, 61], healthcare systems [14], or the government at large [61] have been operationalized in the literature as manifestations of institutional-level stigma and have been associated with negative health outcomes, including poor HIV-related health outcomes [68–71], and may impact PrEP use. Such systems of oppression are largely driven by policies that create and perpetuate discrimination against minority populations, and fueled by political forces that aim to further marginalize minority communities [72], especially in geographical areas of the U.S. that are documenting the highest HIV transmission rates currently [73]. Notably, little research exists to date on PrEP-related stigma on the structural level, such as policies and legislature that shapes PrEP uptake and persistence.

In order to garner a comprehensive perspective on PrEP-related stigma, we aimed to examine existing literature to date reporting on various types of stigma that may limit the impact of PrEP for HIV prevention via access, uptake, adherence, and persistence. Distilling the current state of research on PrEP-related stigma has the potential to suggest future research directions, as well as inform policy and programmatic planning, including where and what types of interventions may be needed to reduce PrEP-related stigma and its impact on PrEP utilization. This inquiry was guided by several research questions, as follows: (1) What are the types of stigma that may have emerged in relation to PrEP?; (2) On which levels of the socioecological planes does PrEP-related stigma manifest most frequently?; and (3) What are the implications for future research, intervention and policy that these findings can guide?

Methods

A scoping review format was chosen for this study given its advantages over a systematic review to describe broad themes and analyze current evidence characterizing stigma, as opposed to the effectiveness of a given intervention [74]. This was especially important given the expected heterogenous and qualitative nature of the evidence [74]. We used the PRISMA extension for scoping reviews checklist as a framework for this scoping review [75], and conducted a series of searches from August 2018 to April 2020 using the electronic databases of PubMed, Embase, ProQuest, and clinicaltrials.gov to identify articles discussing PrEP use and stigma among MSMTW and transmen, including conference proceedings, dissertations, and clinical trials. Our search strategy included a broad range of terms related to stigma such as “stigma”, “shame”, “prejudice”, “homophobia”, “distrust”, “discrimination”, and “racism” alongside synonyms for PrEP (e.g., biomedical prevention, HIV pre-exposure prophylaxis), and men who have sex with men (MSM) and transgender individuals. Our definition of MSMTW included individuals assigned male sex at birth (including cis and nonbinary men, and transwomen) who reported sex with partners who were also assigned male sex at birth (including cis and nonbinary men, and transwomen). The final Boolean query consisted of the stigma-related MeSH headings Social stigma, Shame, Social discrimination, Prejudice, Homophobia, and Racism, combined with title and abstract searches for Stigma, Shame, Discriminat*, Prejudice, Distrust, Homophobia, Homonegativity, Racism, Racial discrimination, Barrier, Attitude, and Accept. For PrEP, we used the MeSH term Pre-Exposure Prophylaxis, and the title and abstract searches Pre-exposure prophylaxis, Preexposure prophylaxis, HIV pre-exposure prophylaxis, HIV preexposure prophylaxis, PrEP, HIV PrEP, and Biomedical prevention. Finally, we combined these terms with the MeSH term Sexual and gender minorities, and the title and abstract terms MSM, Men who have sex with men, Transgender women, Gay, Bisexual, Queer, LGBT*, and transgender men.

Sample

We included studies that explicitly addressed a broad range of PrEP-related issues and stigma, from attitudes to actual use. Our inclusion criteria were (1) studies which included MSM and transgender individuals, (2) studies of stigma, discrimination or cultural beliefs about PrEP for HIV prevention, and (3) studies using quantitative, qualitative, or mixed methods. Exclusion criteria were (1) studies of ciswomen, individuals assigned male sex at birth who did not report sex with other males assigned sex at birth, or people with HIV, and (2) reviews, meta analyses, opinion pieces, or letters to the editor. Only studies reporting on primary data were included. Additionally, stigma is a cultural phenomenon with significant variation across cultures and nations [42, 56, 76, 77]. We therefore included only studies from North America because of our intention to provide guidelines for programming and intervention to reduce PrEP-related stigma within the U.S. Given the highly context-specific of PrEP-related attitudes and practices, other global regions would benefit from guidelines unique to their settings. Based on the inclusion criteria, articles in which PrEP-related stigma themes were not present were excluded during the full text review phase.

Coding

All studies were independently screened in both the abstract and full-text screening by two authors (ALR, EWW), and disagreements about study eligibility were resolved by a third author (LHW). For each included study, two authors (ALR, CLW) extracted the objectives, methods and study population (Table 1). We used a discourse analysis theoretical framework to identify the emerging discourses around PrEP use that shaped views on PrEP users/candidates (e.g., responsible, promiscuous, HIV-infected, etc.) or their reported interactions with other individuals and healthcare systems in the U.S. [78]. To abstract themes, we employed a similar process as undertaken in qualitative data analyses via grounded theory of establishing themes and codes in an iterative process between text and an evolving codebook [79]. We used a thematic analysis methodological approach to gradually develop and reconcile a codebook between two independent coders with conflict resolution by a third independent coder. Specifically, two authors, who had qualitative analysis training and experience (ALR, CLW), began developing the codebook by first reading through a set of five articles independently and coding portions indicative of PrEP-related stigma, after which they convened to compare findings. Guided by the socioecological model framework, the authors first classified the emerging themes on five levels of interest within the socioecological framework (e.g., individual, interpersonal, community, institutional and structural). However, no articles captured by our search reflected structural-level PrEP-specific stigma discourses from primary data analyses, therefore this level was not ultimately included in the current analyses. Initial themes under each level were established based on the authors’ preliminary knowledge of PrEP-related stigma discourses in the literature (e.g., promiscuity).

Table 1.

Study characteristics

Studies	Year(s) data collection	Location	Methodology	N	Sample demographics
Mutchler et al. [65]	2014	Los Angeles, CA, US	Dyadic interviews	48	Mean age = 22.1 (19–28), 86% Black, 88% gay/bi, 12.5% ciswomen
Golub et al. [107]	2013–2014	New York, NY, US	Interviews	160	Mean age = 32.5 (N/A), 57% Black/Latino, 80% gay/bi, ciswomen N/A
Knight et al. [35]	N/A	Vancouver, Canada	Interviews	50	Mean age N/A (18–24), 48% non-White, 32% gay/bi, 2% transmen ciswomen N/A
Farhat et al. [83]	2015	New York, NY, US	Survey	583	Mean age = 44 (N/A), 75% Black, 6% Latinx, 9% gay/bi, 53% ciswomen
Philbin et al. [61]	2013–2014	New York, NY, US	Interviews	31	Mean age = 29 (N/A), race/ethnicity N/A, 100% gay/bi, ciswomen N/A
Lelutiu-Weinberger and Golub [5]	2012–2014	New York, NY, US	Survey, interviews	491	Mean age N/A, 56% Black/Latinx, 100% gay/bi, ciswomen N/A
Eaton et al. [84]	2014	Five US cities	Survey	1274	Mean age = 30 (N/A), race/ethnicity N/A, 76% gay/bi, 4% transwomen, ciswomen N/A
Eaton et al. [14]	2015	City in SE US	Survey	264	Mean age = 31
Cahill et al. [67]	2013	Boston and Jackson	Focus groups	35	Boston: Mean age = 43 (N/A), 73% White non-Hispanic, 100% gay/bi, ciswomen N/A Jackson: Mean age = 23 (N/A), 95% Black, 100% gay/bi, transwomen 5%, ciswomen N/A
Hubach et al. [21]	2016	Southcentral US	Interviews	20	Mean age N/A (N/A), race/ethnicity N/A, 100% gay/bi, 100% cismen ciswomen N/A
Garcia and Harris [85]	N/A	San Antonio, Texas	Survey	159	Mean age N/A (21–30), 100% Latinx, 100% gay/bi, 100% cismen ciswomen N/A
Thomann et al. [29]	N/A	New York, NY, US	Focus groups	24	Mean age N/A (21–50), 100% Black/Latinx, 100% gay/bi, ciswomen N/A
Golub et al. [94]	2015	US	Survey	692	Mean age = 33 (N/A), 23% non-white 22% Latino, 100% MSM/TW, ciswomen N/A
Franks et al. [66]	N/A	Harlem	Focus groups, interviews	37	Mean age = 34 (N/A), 68% Black 8% Asian 2% Latinx, 100% MSM, ciswomen N/A
Grace et al. [80]	N/A	Toronto, Canada	Focus groups, interviews	16	Mean age = 38 (N/A), 69% White, 100% gay/bi, 100% cismen, ciswomen N/A
Mustanski et al. [33]	2016	Chicago, US	Survey	620	Mean age = 21 (N/A), 29% Black 33% Hispanic, 100% gay/bi/transwomen, ciswomen N/A
Grimm and Schwartz [81]	2016–2017	US	Interviews	39	Mean age = 35 (N/A), 69% White 19% Latinx, 100% gay/bi, ciswomen N/A
Pawson and Grov [82]	2015–2016	New York, NY, US	Focus groups	32	Mean age = 35 (N/A), race/ethnicity N/A, 100% gay/bi, ciswomen N/A
Jaiswal et al. [87]	2014–2016	New York, NY, US	Data from longitudinal cohort study	492	Mean age N/A (N/A; “young”), 26% Black 31% Latinx, 100% gay/bi, ciswomen N/A
Dubov et al. [34]	2015	US	Interviews	43	Mean age = 30 (N/A), race/ethnicity N/A, 100% gay/bi, ciswomen N/A
Refugio et al. [88]	2016–2017	San Francisco Bay area	Survey	25	Mean age = 22 (N/A), 40% Latinx, 32% Asian, 100% gay/bi, 100% cismen, ciswomen N/A
Walsh [45]	2016	Midwest, US	Survey	476	Mean age = 35, 21% Black, 100% gay/bi, ciswomen N/A
Brooks et al. [32]	2017	US	Interviews	29	Mean age = 30 (N/A), 100% Latinx, 100% gay/bi, ciswomen N/A

After each set of independent coding, each segment of coded text was reviewed together by the two authors, and the codes were further refined to yield a draft codebook. Then the authors recoded the five articles according to the revised codebook, and coded another set of five articles. The process was repeated three times, after which the two authors coded the remainder of the articles based on the final codebook. The authors categorized codes reflective of a particular socioecological level on which stigma could be classified. A particular code (e.g., “risk promotion”) was marked once in each article where it appeared, even if quotes reflective of it were presented from several interview or focus group participants. Once all articles were coded, a third author (PS) conducted inter-rater reliability analyses and the last discrepancies were resolved by the two coders (ALR, CLW) who examined each instance and considered its classification. The inter-coder reliability was κ = 0.71, indicating adequate agreement.

Reflecting on Turan’s initial framework [46] and in an effort to provide granular information on stigma dimensions, our coding of stigma themes reflects the following logic. Our coding of perceived stigma was that of a general perception of one’s community’s opinions, whereas anticipated stigma assumes the expectation of negative reactions from other individuals. Perceived stigma in this approach generally operates at a higher level of the socioecological model, within the community or society at large, whereas anticipated stigma appears to operate on the interpersonal level. We further distinguished enacted stigma as arising from interpersonal interactions, such that one party is effectively the perpetrator of stigmatization. Defining dimensions of stigma at this level of granularity can promote clarity in future PrEP stigma research, particularly in the quest to reduce negative attitudes and misperceptions to promote widespread acceptance and adoption of PrEP.

Results

General Characteristics of Included Articles

Our initial PubMed search yielded 557 references, resulting in 305 unique studies after 252 duplicates were removed (Fig. 1). Abstract screening excluded 175 references. Full-text review excluded an additional 81 references. An additional 24 articles were excluded during final hand review, 10 of which were papers published from the same data, and 14 of which were deemed to not have a sufficiently in-depth assessment of stigma to allow coding. This yielded a final sample of 25 coded studies. Two additional studies were removed after coding since both studies ultimately yielded no PrEP stigma-related codes (Table 1).

Fig. 1.

PRISMA diagram

Fourteen [5, 21, 29, 31, 34, 35, 49, 61, 65–67, 80–82] (61%) of the 23 coded studies used qualitative or mixed methods such as in-depth interviews or focus groups, and nine (39%) used a cross-sectional survey design [14, 33, 45, 83–88]. The majority (87%) focused mostly or exclusively on MSMTW; one study included men of all sexual orientations [35], one study did not restrict based on sex or gender [83], and one study did not report overall sample demographic information [14]. The earliest date of data collection among these articles was 2012, also coinciding with the year PrEP was US FDA-approved, demonstrating an early quest in the field for manifestations of stigma known to impede health behaviors.

Our gray literature search from Embase, ProQuest and clinicaltrials.gov resulted in six relevant results, including one clinical trial, one poster presentation, and four dissertations. None of these met our inclusion criteria and therefore were not coded.

Prevalence of PrEP Stigma by Socioecological Level

Most instances of identified PrEP-related stigma occurred on the interpersonal level, and included 12 main categories, each of which appeared with different frequency across articles (Table 2). Twelve articles [14, 29, 31, 33, 45, 49, 65, 80–83, 86] reflected discourses of PrEP-related promiscuity, primarily as reported by study participants interviewed or in focus groups, and reflected primarily attributions made by others (actual or potential sex partners, family members, co-workers, providers, or friends) about actual or hypothesized PrEP users. Examples of PrEP use being equated with promiscuity include: “It’s just giving people a free pass. That’s how they take PrEP. They take it as a free pass to go just willy-nilly and do whatever the hell it is they want to do.” [82, p. 1395].

Table 2.

PrEP-related stigma documented in scoping review sample by socioecological levels and thematic findings

Stigma expression	Frequency	Examples
Individual level
Internalized homophobia	4	“You’ve got to accept within yourself that you love and enjoy sex with a man every single day, and you may like it raw 90 percent of the time. But then that’s like accepting, ‘Oh, I’m going to get HIV. Oh, I’m just another fag.’”
PrEP efficacy distrust	4	“I don’t believe that PrEP works, because if it did, then they’d be handing out the pill like they do condoms. I’m gonna need some facts before I try it. I need to see someone do it and get their results.”
Internalized promiscuity	2	”I feel like it would lead me to be more promiscuous.”
Positive health impact	11	“it’s [PrEP] a great method just to prevent the disease. Like it’s the only way HIV and AIDS will actually stop, if people start becoming more conscious about it. And if there’s medicine out there that is allowing us to help us, that’s a great step forward.”
Interpersonal level
Promiscuity	12	“I’ve heard that it’s only for gay men… I had a conversation with someone today and he told me if he was on PrEP he’d be a whore, like that is his get out of jail free card. Um, so I think that kind of stuff. It’s only for gay men, it’s only for whores.”
Risk promotion
Anticipating	10	“A majority of Latino MSM reported that taking PrEP would cause people to stigmatize them as… promiscuous.”
Enacting	10	“Oh I don’t trust that at all. I think it’s just an excuse to sleep around and not use condoms.”
Experiencing	6	”I mentioned to my mom that I was doing a PrEP study to combat HIV. She asked me if I was a sex worker. I’ve been shamed by the guys I used to date, being told that I’m going to die of Hep C and that I’m transmitting HIV to everyone because I’m not using condoms (which was an assumption; I still do).”
HIV-related stigma
Anticipating	10	”I keep my medication in my room and not in the bathroom where I used to keep it because either my little brother or my mom might see it and they’d be like, ‘Hmm, why is this person taking this?’ Maybe they’ll assume that I have HIV.”
Experiencing	4	”I think one of my friends I had to tell exactly what it was because they saw the bottle and I think they looked up what it was for and they thought I had HIV because it was an HIV med.”
Enacting	2	“Several salient themes emerged from the discussion starter question: what comes to mind when somebody tells you they are on PrEP?… Outlier responses to this opening question included the view… that the PrEP user was HIV-positive
Negative relationship impact	8	“When I was having sex, I would take the pills and my partners would be like, ‘Why are you taking those pills?’… Sometimes it would never get to the intercourse part. It would just stop the night. They would be mad and leave.”
Homophobia/other ing	6	“In expressing their concerns about PrEP, participants, including many who identified as gay, bisexual, or MSM, frequently drew on stereotypes that link promiscuity and condomless sex with a ‘gay lifestyle’ and used those prejudices to underpin their negative opinions about PrEP.”
General	6	“Some men discussed experiences of PrEP-related judgment, stigma, or rejection when trying to connect online with prospective sexual partners.”
Community level
Anticipated homophobia	4	“One said that stigma related to gay sex might be a barrier to people seeking PrEP for HIV prevention.”
Responsibility to educate peers	7	“Men who were currently on PrEP shared the obstacles they overcame and used the experience as an opportunity to educate others. Disclosure to peers and other men on social network applications allowed for linking men seeking PrEP to known providers who were prescribing it for HIV prevention.”
Institutional level
Provider distrust	10	“Historically, African Americans have an aversion to any kind of healthcare, or any kind of medicine. So we, as African Americans, historically prefer natural healing or prayer. And we kind of, we avoid doctors.”
Provider discrimination	7	“She [his provider] said that I should take PrEP and I was like, ‘Uh, I’m ok.’ And she was like, basically, you’re gay and you’re having sex, surely, and active so you should do it… She went on about it and was saying, ‘You’re gay and you’re young, you have a lot of sex you should take PrEP.’ And I’m like, ‘You know, you don’t know me lady.’
Governmental/pharmaceutical distrust	7	“Some men explicitly referred to historical abuses by pharmaceuticals and research (e.g., Tuskegee Syphilis Study), and how they profit from [black men who have sex with men]”
Healthcare distrust	5	“Mistrust of both the pharmaceutical industry and healthcare providers was widespread.”

The next three themes fell in the category of “risk promotion,” namely anticipating and experiencing situations in which PrEP use was framed as promoting sexual risk. Specifically, 10 articles [21, 31, 34, 49, 65, 66, 80–82, 85] reflected that participants, in considering or using PrEP, anticipated encountering discourses of risk promotion from others (e.g., “they’ll tell people as soon as you leave the table that you’re doing that ‘cause you wanna have numerous tricks or anonymous encounters… you’re only using PrEP to rationalize your true behavior.” [21, p. 321]). Further, 10 articles [14, 21, 29, 33–35, 61, 65, 81, 82] presented data on participants endorsing (or enacting) beliefs that PrEP is conducive of risk promotion (e.g., “these men recalled ‘people being slut shamed for using PrEP. My friends had negative thoughts and things to say about it.” [21, p. 321]). Lastly, six articles [21, 31, 34, 66, 80, 81] provided data from participants who had encountered others framing their PrEP use as promoting risk (e.g., “once I told them that I was on PrEP because they assumed that my whole lifestyle is changed…one of the regulars that I had previous to going on PrEP decided to stop doing me because he assumed that I would instantly become like a receptacle…for every gay plague known to man..” [80, p. 26]).

PrEP use in relation to HIV stigma appeared in 12 articles [5, 21, 29, 31, 34, 49, 61, 65, 66, 81, 85, 87]. The most common theme was anticipated HIV stigma (e.g., “‘People don’t like taking any medicine in front of people. Maybe they feel like a stigma would develop from what you are taking? People be nosy, like what’s that you taking?” [61, p. 287]). Other themes included having experienced HIV stigma (e.g., “I think one of my friends I had to tell exactly what it was because they saw the bottle and I think they looked up what it was for and they thought I had HIV because it was an HIV med.” [31, p. 6]), and enacted HIV stigma (e.g., “For me, if someone just said so-and-so’s using PrEP and I knew what PrEP was at that time, I would question what is their HIV status” [66, p. 1145]).

Another interpersonal-level theme was related to the negative impact PrEP had on romantic relationships, which appeared in five articles [29, 31, 34, 66, 80]. Expressly, once one of the partners considered or began taking PrEP, the other partner either confronted them for not trusting their monogamy or for wanting to have sex with other people:

I am recently single due to my partner not understanding why I take PrEP. He felt PrEP was interfering with the possibility of a commitment. He asked me to stop taking Truvada as a show of good faith for a relationship, but I knew his part was fickle at best.

[34, p. 1836].

Six articles [29, 34, 35, 61, 82, 85] reported associations of PrEP with homonegativity, specifically related to gay men being promiscuous (e.g., “I’ve heard that it’s only for gay men… someone today… told me if he was on PrEP he’d be a whore, like that is his get out of jail free card.… It’s only for gay men, it’s only for whores.” [29, p. 776]). Four articles [31, 34, 80, 88] reported general stigmatizing PrEP-related references (e.g., “Instead of continuing these risky behaviours and using HIV medication, maybe people should just stop the behaviour, right?.” [35, p. 7]).

The next level on which PrEP-related stigma was frequently manifested was at the institutional level, under five main coded categories, as follows. Ten articles [5, 21, 29, 31, 61, 67, 81, 85, 87, 88] revealed PrEP themes related to provider distrust, such as Black and Latinx MSMTW reporting having to talk to their doctor about sex being a barrier to seeking PrEP [5], followed by seven articles [21, 29, 31, 67, 80, 81, 88] reporting provider discrimination (e.g., “My previous doctor, who was a man, just told me to have sex with women.” [67, p. 14]). Five articles [14, 29, 61, 65, 85] revealed themes of distrust in the government and/or pharmaceutical companies (e.g., “A more common assumption was that pharmaceutical companies were encouraging the use of PrEP while withholding a cure for HIV in order to generate income from medication sales.” [65, p. 494]). Finally, for this level, five articles [14, 29, 61, 65, 85] contained themes of general healthcare distrust in promoting PrEP (e.g., “Among [Black men and transgender women who have sex with men], believing that the CDC cannot be trusted in their messaging regarding PrEP was associated with a lower interest in using PrEP [14]).

PrEP-related stigma at the individual level was reported in 17 papers, where three main PrEP-related categories emerged: four articles [5, 34, 61, 84] revealed themes of internalized homonegativity in association with PrEP use [84], four articles [5, 29, 45, 67] indicated distrust in PrEP efficacy and two articles reporting instances of internalized promiscuity in relation to PrEP use (e.g., “Like you are not getting the big one, but you are also opening yourself up to syphilis, gonorrhea, all of these. I feel like it would lead me to be more promiscuous.” [21, p. 324]).

Only one main PrEP stigma-related category emerged related to community level stigma, namely four articles reflected general community associations of PrEP use with anticipated homophobic (“homonegative”) reactions from others (e.g., “A small percentage of participants (6.3%, n = 10) were concerned that PrEP use would be associated with negative beliefs about gay men’s sexuality and would intensify negative beliefs about the gay community” [49]).

Of note, within many of the studies, authors noted recurring discourses that defined PrEP use in a positive light, e.g., challenging stigma. These instances occurred at both the individual and community level, with the former referring to individuals recognizing the benefits of PrEP on one’s physical and mental health (11 articles [21, 29, 31, 33, 35, 49, 65, 66, 80–82], e.g., “I’m 51. I stopped counting my friends who died of AIDS around 95. I say grab this. Hooray for PrEP.” [81, p. 10.]). The latter reflected a responsibility towards protecting one’s community from HIV by “spreading the word” about PrEP to “educate others”, by conveying facts, dispelling misconceptions and reducing common PrEP attributions of “promiscuity,” “risk promotion,” or “anticipated HIV stigma” (e.g., “Rather than stigma or shame, many participants discussed being “proud” and “liberated” because of their PrEP use: “I feel proud because I know that I am doing something positive… I know that I am doing the right thing by keeping myself and other people healthy” [80, p. 26]).

Stigma Dimensions

Based on an expanded stigma framework that includes challenging stigma [38, 46], we further organized identified stigma dimensions in each coded study (Table 3). All stigma dimensions were represented in the coded studies. Experienced stigma was primarily found on the interpersonal level, but also manifested on the institutional level as discrimination from healthcare providers. Enacted stigma was found on the interpersonal level, while perceived stigma occurred on the interpersonal and institutional levels. Anticipated stigma was identified on the interpersonal and community levels, and internalized stigma on the individual level. Expressions of challenging stigma were found on the individual and community levels.

Table 3.

PrEP-related stigma documented in scoping review by stigma dimension and thematic findings

Stigma dimension	Examples
Experienced stigma	“One of my partners was like, ‘Whoa, whoa. What does this mean? What are you doing?’ In other words, indicating that just by taking the pill this means that I’m willy-nilly having unprotected sex.”
	“If doctors make me uncomfortable for being gay, then the last thing I want to do is tell you about my sex life … There are a lot of doctors who throw their own personal opinion into their perspective. One asked me if I’m homosexual. That made me uncomfortable.”
Enacted stigma	“For me, if someone just said so-and-so’s using PrEP and I knew what PrEP was at that time, I would question what is their HIV status… [Or] they could just be very—really promiscuous.”
	“I feel like the only people that really need it is if you’re in a relationship, you’re negative and your partner is positive. That’s the only reason why I feel like you should be taking PrEP. Other than that, it’s just an excuse to slut around.”
Perceived stigma	“The idea is that if you go on PrEP, you are like very wanton and want to be barebacking all the time and that you are not safe. In other words, you are one of those petri dish people.”
Anticipated stigma	“I keep my medication in my room and not in the bathroom where I used to keep it because either my little brother or my mom might see it and they’d be like, ‘Hmm, why is this person taking this?’ Maybe they’ll assume that I have HIV.”
Internalized stigma	“I know I still work hard at not letting my own freedom of sexual expression and identity feel like anything but healthy and positive. I know that PrEP for me means embracing and owning that ‘I made it’ despite the risks … There’s a bit of ‘survivor guilt’… All of that gets put in the mix when it comes to the shaming.”
	“The shaming comes from fear and the majority of the stigma is within the LGBT community … Within the LGBT community, there is a lot of internalized homophobia attached to PrEP and these people are afraid of having the sex they want. That is attached to shaming as well.”
	“If somebody knew I was asking about that pill. Then there is a stigma that goes along with that. And I think that people will obviously look at you differently…”
Challenging stigma	“I feel like if they’re [on PrEP], they’re not only protecting themselves. It’s also for the well-being of other people that they’re having sex with. I don’t think there’s anything bad. I think it’s all positive.”
	“I post about it all the time. People filter their stuff to me, as well. There was a moment there when I feel like I was answering PrEP questions daily with gays that I know that were like, ‘Tell me about PrEP,’ or, ‘I don’t know about it.’ Now people share new stories about PrEP with me.”
	“Because everybody needs to know about it. There’s a few things. I am trying to abolish stigma around sexuality. I am trying to raise awareness for sexual health and the people who follow me are not just homosexuals, so the more times I can interact with just one heterosexual person, or 10 or 50 or 100, and be like, ‘Hey, there’s a medicine. Go talk to your doctor about it. It’s like birth control for HIV.’”

Discussion

This scoping review of literature published through April 2020 revealed significant and persistent PrEP-related stigma surrounding this highly efficacious biomedical prevention tool. Multiple types of stigma emerged on four levels of the socioecological model: individual, interpersonal, community, and institutional. The most prevalent types of PrEP-related stigma occurred on the interpersonal level (e.g., discourses around promiscuity and risk-promotion), followed by the institutional (e.g., provider distrust) and individual (e.g., PrEP efficacy distrust) levels. Community-level PrEP stigma was the least represented (e.g., anticipated homonegativity). A notable finding was the emergence of PrEP-positive attitudes at the individual (e.g., empowerment, health self-efficacy, improved mental health) and community (sense of responsibility of educating others on the benefits of PrEP) levels. To support the uptake potential of this paradigm-shifting biomedical tool, we discuss our findings as to guide future intervention research towards improved PrEP promotion and clinical implementation.

Sex negativity dominated the interpersonal level focused on judgments and shaming of certain specific behaviors, with risk-promotion (e.g., engaging in condomless sex) and promiscuity (e.g., having multiple partners) being the first and second most common manifestations of PrEP-related stigma. Framing PrEP as promoting of sexual risk was just as frequently endorsed as it was anticipated by participants in these studies, suggesting that wide-canvasing interventions are needed to further emphasize the value of PrEP and the health-bolstering accountability rather than promiscuity of PrEP users. It also appears that beliefs of risk compensation (e.g., decreased condom use once on PrEP) continue to persist, suggesting that interventions targeting healthcare providers and communities would benefit from conveying evidence-based findings around unfounded postulations of risk compensation among PrEP users [11, 89–92].

To further counteract pervasive negative views on PrEP, far-reaching attitude-changing interventions, likely via social media (e.g., Twitter, Instagram, Facebook) and public campaigns (e.g., on buses, television commercials, and healthcare facilities) may alter these trends to further increase awareness around PrEP benefits and promote a discourse of empowerment and responsibility towards one’s health and the health of the community at large. Relatedly, the positive attitudes many PrEP users endorsed around having a sense of responsibility to educate others about the benefits of PrEP at the community-level may be considered as both a shift away from stigma towards resilience, and an avenue to promote PrEP-positive messaging that may permeate communities to reduce attitudes of risk, promiscuity and homonegativity. Community-level interventions remain critical, especially in the light of PrEP stigma being partially rooted within the LGBTQ community itself [34, 93, 94].

The institutional level followed the interpersonal level in reports of PrEP-related barriers. Reverberating a multitude of reports of provider unwillingness or unpreparedness to counsel on and prescribe PrEP [27, 67, 95–102], our review contributes accounts from patients experiencing a range of institutional-level negative encounters when seeking PrEP, which may be characterized as an intersection of homonegative and sex-negative views. Provider-level barriers thus persist, close to a decade after PrEP’s FDA approval. These reports speak to the modest success of continuing education to influence clinical practice in support of PrEP, demanding more rigorous intervention efforts to assess the most efficacious approaches to integrating this prevention modality into standard-of-care within primary care, emergency departments, and community programs [103–105]. Clustering PrEP expertise within infectious disease and sexual health clinics, or within LGBT-serving clinics, will continue to limit access for patients who may not utilize these care points and constitute missed opportunities for essential PrEP-related education for primary care providers [5]. The current limited PrEP availability in select points of care may also perpetuate the stigmatizing idea that PrEP is only for certain populations with high risk behaviors [29, 35, 106], and not capture the broader approach of vulnerability to HIV due to a multitude of socially-determined factors (e.g., intersectional stigma, low resources, poor healthcare access). Lastly, although not highly prevalent, distrust in public health entities, the government, pharmaceutical companies, and medical institutions persists, which may be perceived as promoting PrEP for profit and not for the well-being of its users. Building patient-centered PrEP counseling approaches, where PrEP candidates engage in shared decision making as they consider this prevention option, alongside others (e.g., barrier methods, abstinence) [107], may be an avenue to build trust for those who continue to be apprehensive about institutional motives behind PrEP promotion.

At the individual level, and related to the above, themes of PrEP efficacy distrust emerged, even after PrEP efficacy had been confirmed in multiple large trials and demonstration studies [104, 108, 109]. It is possible that scientific findings are not adequately disseminated across levels beyond medical and academic circles, in order to reach consumers. The tools of intervention research may be leveraged in assessing the most effective attitude-change strategies in conveying factual PrEP information, such as having audiences identify with and trust the “messengers” who may be peers or respected leaders and organizations [110]. While the least number of themes related to PrEP stigma manifested at the community level, efforts to reduce perceptions of negative PrEP associations with the LGBTQ community are worth considering. Campaigns representative of diversity, which are visible to the general population rather than exclusive to certain so-perceived “risk groups” present the promise of normalizing PrEP as an option to prevent HIV for anyone who is or may become sexually active. Family-level interventions via pediatric and adolescent clinics may lend effective avenues for PrEP awareness-raising and potential uptake by upcoming youth generations, and follow a similar successful path taken for human papilloma virus prevention [111]. This recommendation supports the infusion of PrEP in primary care, sexual health curricula and student health services, such that the odds of this medication becoming a standard-of-care option similar to vaccinations or routine HIV/STI testing, are increased.

Our findings uncover new potential avenues for PrEP promotion, within society at large and clinical practice, by revealing distinctly emerging PrEP-positive discourses challenging of stigma, and suggestive of new research directions. While our primary goal was to establish the extent of PrEP stigma literature, a clear message emerged across studies reflective of positive evaluations of PrEP [29, 33, 35, 65, 66, 80–82]. These conveyed suddenly “game-changing” messages of alleviated mental and physical health threats across over three decades of the HIV/AIDS epidemic. Our findings uncovered discourses of empowerment, personal and community responsibility, and the unprecedented opportunity to dissociate sexuality and pleasure from the previously omnipresent fear of “contagion”, associated stigma and death [112]. While there is emerging interest in this direction [113], no empirical work to date has challenged PrEP-associated stigma (e.g., homonegativity, promiscuity) at its core. Several of the studies included in this review described participants’ positive views on PrEP, without explicitly discussing mechanisms to challenge stigma within the context of PrEP. The specific concept of challenging stigma derived from popular social media discourses reclaiming the derogatory term “Truvada whore” [28, 114]. Following these early studies, researchers have identified challenging stigma as a prominent theme in stigma discourse [38, 115], however, challenging stigma is yet to be adopted by the PrEP stigma intervention research to explore its potential to reframe PrEP-negative discourses, on multiple socioecological levels, to increase PrEP utilization.

Notably, several PrEP-related stigma interventions are under way. Our search of clinicaltrials.gov and collective knowledge of active PrEP stigma research revealed five ongoing studies that specifically aim to address PrEP stigma. “Empowering with PrEP” [116] includes PrEP stigma as a secondary outcome measure, defined as “any stigma the participant might have about PrEP or those who use PrEP. In “Value Affirmation and Future Selves” [117], the primary outcome measure is PrEP adherence. The study design is a parallel group randomized, controlled clinical trial to test a behavioral intervention that aims to increase individual resilience against PrEP-related stigma. “Project Jumpstart” [118] uses cognitive behavioral theory to develop an intervention model based on the HIV Stigma Framework and the Medication Necessity-Concerns Framework to increase PrEP uptake, adherence, and persistence. “A Cognitive Behavioral Therapy Group Intervention” [119] examines effective coping, including internalized and anticipated stigma, and medical distrust, as a mechanism of PrEP uptake among Latinx MSM. Finally, “PrEP2Prevent” (pending; R34DA050531; PI: Kipke) entails the development of a mobile app to support PrEP navigation, and will also include evaluation of PrEP stigma as a mediating mechanism for PrEP engagement.

Much of the formative work on challenging stigma is rooted within resilience theory [120], utilizing a strength-based approach instead of focusing on deficits, which poses the risk of reinforcing negative stereotypes [50, 115, 121]. A resilience approach supports the processes through which individuals navigate and counter adversity [122], which may be translated into interventions. For example, individual-level, empowering interventions could be embedded into PrEP counseling sessions, where documentation is provided on barriers to health that may be removed by PrEP use, such as high protection against HIV, improved mental health and general health self-efficacy and accountability, and lowered stigma against HIV-positive people. Provider-level interventions that challenge stigma could entail modules focused on the relationship between provider stigmatization of patient identities, leading to health inequities. This approach would raise awareness of stigma-driven differential treatment by providers of certain groups that is detrimental to their health. For example, providers should be made aware of the evidence indicative of how providers often discuss PrEP with highly sexually active patients by making attributes of promiscuity, or shaming patients who may have multiple sexual partners or same-sex partners. Intervention components that would remove both provider implicit and explicit bias around sexuality and shift the focus on PrEP as an avenue for individual empowerment and accountability would directly address PrEP stigma, increase patient trust in providers and foster affirming patient–provider communication. Lastly, adopting an intersectional perspective, these interventions may layer sexuality bias reduction with reducing racial/ethnic bias of white providers, which continues to linger and lead to underserving people of color. Simultaneous patient–provider interventions may be capable of orchestrating attitudinal and behavioral change on both levels.

A clear gap revealed by our review is the relative lack of studies investigating structural-level stigma, including systematic discrimination in laws and policies both in civic society at large, and in healthcare-related areas such as Medicaid [55]. A multi-level approach to address stigma has been called for [123], and literature has begun to emerge addressing this need [124]. Furthermore, given the complexity of stigma manifestations, an updated review of stigma measurements would be beneficial in bolstering research around stigma reduction interventions, particularly those adapted to measure PrEP-related stigma. Since Earnshaw’s review of HIV stigma mechanisms measures in 2009 [125], a number of validated instruments for measuring stigma have emerged [41, 42]. Our scoping review illustrates a heavy focus on qualitative methods in the quest for understanding the operationalization of stigma on all the levels of the socioecological model. Longitudinal, quantitative work is needed to nuance our understanding of stigma processes beyond hypothesis generation, and to establish causal relationships around PrEP uptake, adherence and persistence.

Limitations

Several limitations emerged. Because stigma is determined by social, political and cultural factors, we did not include studies outside of North America, given our scope of recommending future directions in PrEP promotion that are contextually-tied. Thus, studies reflective of PrEP attitudes in other regions of the world were omitted, reducing potential for immediate generalizability to other contexts without considerable inquiries within local PrEP-related discourses. Further, the time span for this literature is for the time being limited, given that the earliest publication was 5 years ago. This both restricts the sample of potential data points and our ability to understand fluctuations in PrEP-related stigma, including its potential attenuation in favor of increasingly positive attitudes across time. This suggests the benefits of continued monitoring of this literature to observe such potential changes. Additionally, the reviewed literature focused on currently FDA-approved PrEP modalities (e.g., daily oral regimens), and stigma related to alternative PrEP use strategies (e.g., on-demand, long-acting) is worth investigating as this literature emerges. Importantly, no evident research has investigated PrEP-related stigma towards and among transmen. This is a notable gap in knowledge given that many transmen who have sex with men are in fact at risk for HIV and experience a range of unique stigma types likely to affect their PrEP uptake and persistence [37]. Lastly, existing PrEP stigma literature did not include HIV-positive individuals whose opinions are likely to be important given they may be ones discussing this strategy with their partners.

Conclusion

This scoping review revealed multiple manifestations of PrEP-related stigma, at four levels of the socioecological model, including in the most recently published literature. While interventions to directly modify negative PrEP attitudes at various levels need to continue, PrEP proponents may be well-served by leveraging increasing PrEP-positive discourses that appear to be occurring organically and are already challenging manifestations of PrEP-related stigma. Adopting a resilience and strengths-based approach could increase consumer and community awareness of and education around PrEP benefits and efficacy, and promote an affirmative discourse of the health value of PrEP to revert negative attribution of sexual risk promotion and promiscuity. Furthermore, direct efforts to increase provider willingness to educate themselves around and promote PrEP routinely remain essential, in order to reduce provider bias and patient distrust, and align with the national strategy to End the HIV Epidemic in the U.S. [7].