WILLINGNESS TO USE MICROBICIDES AMONG FEMALES WHO USE UNREGULATED DRUGS IN VANCOUVER, CANADA

Abstract

Microbicides are an emerging HIV-focused biomedical intervention offering protection against HIV. Despite potential benefits, willingness to use these products has not been well studied, especially among females who use unregulated drugs. Between June 2021 and May 2022, data were drawn from two prospective cohorts of people who use drugs in Vancouver, Canada. Analyses focused on participants who were female sex at birth and sexually active. Multivariable logistic regression identified correlates of willingness to use a vaginal ring with microbicides. Awareness of microbicides was also assessed. Among 216 participants (median age 36; 47.2% Black, Indigenous, or a Person of Colour), only 32 (14.8%) reported prior awareness of microbicides. Once described, 57 (26.4%) expressed willingness to use a vaginal ring. Independent correlates of willingness included recent access to prescribed alternatives to unregulated drugs (AOR = 3.30, 95% CI = 1.19–9.15), willingness to take pre-exposure prophylaxis (PrEP) (AOR = 14.87, 95% CI = 6.38–34.65), and recent sex work engagement (AOR = 2.92, 95% CI = 1.19–7.15). Findings indicate low awareness and willingness to use microbicides among females who use drugs in Vancouver, Canada. While microbicides appear to offer important opportunities as a biomedical intervention, initial low levels of reported willingness indicate the impact may be limited.

INTRODUCTION

Human immunodeficiency virus (HIV) remains a significant public health concern, with over 39 million people living with the virus worldwide as of 2023 (World Health Organization, 2023). In Canada, an estimated 65,270 people were living with HIV by the end of 2022 (Public Health Agency of Canada, 2024b). Although new HIV infections in Canada have declined substantially since the 1990s, the risk of HIV exposure remains unevenly distributed. In 2022, the annual incidence rate of HIV was 5 per 100,000 in the general population, compared to 494 per 100,000 among people who use injection drugs (Public Health Agency of Canada, 2024a).

Injection drug use is a key driver of HIV transmission in Canada, but its impact is also not uniform across populations. National surveillance data by the Public Health Agency of Canada (2024a, 2024b) points to significant sex-based differences in exposure pathways. While heterosexual contact was the most common mode of transmission overall in 2022 (39.4%), this was closely followed by male-to-male sexual contact (36.0%) and injection drug use (18.2%) (Public Health Agency of Canada, 2024b). Among people assigned male at birth, over half of new infections were attributed to male-to-male sexual contact (52.2%), while heterosexual contact and injection drug use accounted for 26.5% and 13.6%, respectively. In contrast, among people assigned female at birth, heterosexual contact (68.1%) and injection drug use (28.4%) were the most prevalent pathways of exposure to HIV, together accounting for nearly all new cases (Public Health Agency of Canada, 2024b). These gendered patterns in new HIV diagnoses underscore the need for prevention and treatment strategies that respond to the specific risks faced by females who use drugs and have sex with males.

While HIV incidence rates among people assigned female at birth have remained relatively stable over the past decade, around 2.4 per 100,000 population (Public Health Agency of Canada, 2023), females who use drugs face distinct biological and structural risks (Kerr et al., 2016; Mahathir, 1997; Morrison-Beedy & Passmore, 2015a). Power imbalances within sexual relationships often limit women’s ability to negotiate condom use, and unprotected sex with a male partner remains the most common means of HIV transmission among women (Mertenskoetter & Kaptur, 2011; Morrow, Fava, Rosen, Christensen, et al., 2007a). Substance use can further reduce women’s agency in negotiating safer sex, exacerbating existing risks (Ostrach & Singer, 2012). Although needle sharing poses a direct risk (Parry et al., 2009), research has found that high-risk heterosexual activity is more strongly associated with HIV acquisition among females who use drugs than injection-related behaviours (Strathdee et al., 2001).

In response to intersecting risks that people assigned female at birth face, new biomedical tools have emerged to expand HIV prevention options for females who have sex with males. One such intervention is a vaginal microbicide ring, which releases anti-HIV medication over time to prevent transmission during vaginal sex (Fred Hutchinson Cancer Center, 2022). Phase III clinical trials led by the United States (US) National Institute of Health (NIH) involving vaginal rings containing Dapivirine, a non-nucleoside reverse transcriptase inhibitor, found that using the ring as prescribed lowered HIV risk by 56% (Baeten et al., 2016; Mirembe et al., 2023). Additional studies found higher adherence was associated with greater effectiveness, with up to 75–91% reduction among participants with higher adherence (Brown et al., 2020; Dabee et al., 2022). The ring can be inserted monthly without support from a healthcare provider, offering a discreet, self-initiated, and low-maintenance alternative to other forms of pre-exposure prophylaxis (PrEP), such as daily pills or regular injections. Because it does not require negotiation at the time of intercourse, the ring may enhance autonomy and expand prevention options for women in contexts where they have limited control over condom use (Farr Zuend et al., 2021; Fred Hutchinson Cancer Center, 2022). Importantly, at the time of writing, microbicides are not currently available for use in the U.S. or Canada, although they have been approved for use in South Africa (Zhernov et al., 2024).

While the efficacy of microbicides is still being investigated, and notable challenges remain, their potential to prevent HIV transmission will be impacted by the willingness of key populations to engage with the intervention. Previous studies investigating willingness to use microbicides among females in the general population found that product characteristics affect willingness to use, suggesting that future microbicide development should continue to address these concerns (e.g., messiness, appearance, effect on sexual pleasure) (Morrow, Fava, Rosen, Vargas, et al., 2007b). Another study exploring willingness among urban adolescent girls found that factors impacting microbicide use included a fear of side effects, general mistrust of research, and concerns with their partners’ perceptions (Morrison-Beedy & Passmore, 2015b). Women who use drugs face unique challenges and barriers to HIV prevention (Latkin et al., 2003; Parry et al., 2009), many of which stem from structural factors related to substance use that hinder their ability to follow medical guidance and consistently use prevention products (Des Jarlais, 2000; Marshall & Wood, 2010; Parry et al., 2009). Extrapolating findings from the general population to PWUD is therefore limited.

While select studies have assessed women who use drugs’ acceptability to use microbicides (Hammett et al., 2000; Weeks et al., 2004), they did not specifically consider vaginal rings. The focus of many prior microbicide acceptability studies has been on gel, moisturizer, or other lubricant products. Importantly, these studies have identified product characteristics as a factor influencing microbicide acceptability (Mensch et al., 2012; Montgomery et al., 2010; Morrison-Beedy & Passmore, 2015b; Weeks et al., 2004; Woodsong et al., 2013). Commonly reported reasons for failing to use the product during sex among women who use drugs were forgetting to apply the product, not wanting to interrupt sex, partner refusal, and inconvenience of use (i.e., being in a bad location) (Weeks et al., 2004). These studies also found that a small number reported being too high or drunk to apply the product before sex (Weeks et al., 2004). Another study investigating the acceptability of different microbicide products found that many women who use drugs had conflicting opinions about a microbicide product based on its level of messiness (Hammett et al., 2000). Some women strongly favoured the product because they considered it to be “not too messy” while others strongly disliked it for the opposite reason, citing it as “too messy” (Hammett et al., 2000). Given that microbicide use by means of a vaginal ring would resolve many of these concerns, characterising willingness to use microbicides in the specific context of a vaginal ring is of benefit.

To address gaps in literature on willingness to use microbicides delivered via a vaginal ring among populations at elevated risk of contracting HIV, particularly females who use unregulated drugs, we examined awareness of and willingness to use a vaginal microbicide ring. Our analysis focused on sexually active females who have sex with males in two community recruited cohorts of people who use unregulated drugs in Vancouver, Canada. To our knowledge, this is the first paper to investigate willingness to use microbicides in the form of a vaginal ring among females who use unregulated drugs. Given the unique context of HIV prevention for women who use unregulated drugs – including structural vulnerability and barriers to engaging with the healthcare system, which may limit access to traditional prevention measures such as PrEP – examining willingness to engage with novel interventions like microbicides is important. Broadening the range of available prevention options acknowledges that different modalities meet different needs across contexts and may support greater autonomy and uptake among this population.

METHODS

Data for this study were derived from two ongoing longitudinal cohorts of PWUD in Vancouver, Canada: the At-Risk Youth Study (ARYS) and the Vancouver Injection Drug Users Study (VIDUS). Details of these studies and their harmonized procedures have been previously described in detail and published elsewhere (Strathdee et al., 1997; Tyndall et al., 2001; Wood et al., 2006). Briefly, to be eligible to enrol, participants must have used drugs (other than or in addition to cannabis, alcohol, tobacco) within the previous month, resided in the Greater Vancouver area, and provided written informed consent. The ARYS cohort enrols participants aged 14–26, who are street-involved, defined as being without stable housing or utilising services for youth who are experiencing homelessness in the last month. The VIDUS cohort includes participants who are at least 18 years old, are HIV-negative, and have injected drugs within the last month. The studies use harmonized data collection procedures to allow for pooled analyses. Participants complete an interviewer-administered questionnaire at baseline and every six months thereafter. The questionnaire collects data on demographics, substance use patterns and associated risks, income generation activities, and health and social service engagement, among others. All participants received a $40 CAD honorarium at each study visit during the present study. The University of British Columbia, Providence Health Care, and Simon Fraser University Research Ethics Boards approved these cohort studies during the present study.

Participants who completed an interview between June 2021 and May 2022 were included in this study. Due to the declaration of the COVID-19 public health emergency in March 2020, all in-person study activities were halted until July 2020. Between July 2020 and February 2022 study interviews for participants already enrolled in the cohorts were held remotely via telephone or videoconferencing. In person study interviews recommenced in March 2022. Data collection procedures during the pandemic have been described in detail and published elsewhere (McAdam et al., 2022).

Data from participants who reported being sexually active in the past six months (defined as any sex including oral) and assigned female at birth, were eligible for this analysis. The terms “women,” “females,” and “people assigned female at birth” are used interchangeably, as are the terms “men,” “males,” and “people assigned male at birth.” The terms “women” and “men” are used for ease of readability; however, our sample consists of people assigned female at birth. This reflects the physiological relevance of vaginal microbicides. At the same time, we recognize that socio-structural factors shaping HIV risk, such as stigma and discrimination, also affect individuals not assigned female at birth who identify as women and share similar vulnerabilities. While not our intent, we acknowledge that conflating sex and gender may obscure the distinct experiences of transgender, nonbinary, and gender-diverse people, whose HIV prevention and treatment needs remain underexamined.

To assess for awareness of microbicides, participants were asked the following: “Have you ever heard of microbicides in the context of HIV?” (yes vs. no). After this question, participants were provided with the following information explaining what microbicides are in the context of HIV: “Microbicides are a new medication that is being developed and may reduce the risk of HIV infection during sex in people who are at risk of HIV. Microbicides come in various forms including vaginal rings. Clinical trials to date found a small portion of women participants experienced some mild and temporary side effects such as uterine bleeding and pelvic pain.” The primary outcome of interest was willingness to use microbicides and was based on the following question: “Would you be willing to wear a small vaginal ring approximately the size of a thick hair elastic containing microbicides that might reduce the risk of HIV infection during sex?” (yes vs. no). Participants who answered “yes, definitely” or “yes probably” were coded as yes and those who answered “no, probably not” and “no, definitely not” were coded as no. Participants who answered “unsure” or did not answer this question were excluded from the analysis.

It was hypothesized that willingness to use microbicides would be impacted by behavioural patterns relating to healthcare service utilisation, engagement in sex work, and substance use patterns. For example, it was hypothesized that participants who have established connections to the healthcare system, such as those who have recently accessed prescribed alternatives to unregulated drugs, defined as receipt of selective pharmaceutical opioids or stimulants from a physician (Canada, 2021; Ministry of Mental Health and Addictions, 2021), were expected to have an increased odds of being willing to use microbicides. Accessing such alternatives typically requires regular interaction with healthcare providers, making it a strong indicator of ongoing engagement with the healthcare system.

We hypothesized that recent healthcare service access would signal increased trust of and reliance on the healthcare system. Additionally, it was hypothesized that those who were at an increased risk of contracting HIV, including those engaged in sex work, those with multiple partners, and those engaged in unsafe sex (i.e., not using a condom), would also be more willing to use microbicides. As such, variables hypothesized to be associated with our primary outcome included: age (> 35 vs. ≤ 35); race/ancestry (Black, Indigenous, or a Person of Colour (BIPOC) vs. white); experiencing homelessness (yes vs. no); Downtown Eastside (DTES) residence, a neighbourhood in Vancouver with a well characterized open drug scene (Wood et al., 2004) (yes vs. no); employment, defined as having a regular job, temporary work, or self-employment (yes vs. no); self-identifies as part of the Two-Spirit, lesbian, gay, bisexual, or transgender (2SLGBT) community (yes vs. no); any injection drug use (yes vs. no); at least weekly cocaine use (yes vs. no); at least weekly crack cocaine use (yes vs. no); at least weekly heroin/fentanyl/down use (yes vs. no); at least weekly crystal methamphetamine use (yes vs. no); at least weekly non-medical prescription opioid (NMPO) use, defined as taking prescription opioids that were not prescribed or taking prescription opioids only for the experience or feeling they caused (yes vs. no); engaged in opioid agonist therapy (OAT) (yes vs. no); any drug or alcohol treatment including detox, recovery house, and treatment centre (yes vs. no); receipt of prescribed alternatives to unregulated drugs (yes vs. no); had sex with men (yes vs. no); engaged in unsafe sex, defined as any form of unprotected sex (yes vs. no); self-reported hepatitis C (HCV) infection (yes vs. no); self-reported ever having a sexually transmitted infection (STI) (yes vs. no); experienced opioid withdrawal (yes vs. no); experienced a non-fatal overdose, defined as an acute reaction or overdose following drug use (yes vs. no); self-reported history of taking pre-exposure prophylaxis (PrEP) (yes vs. no); willingness to take PrEP (yes vs. no); engagement in sex work, defined as exchanging sex for money, gifts, food, shelter, clothes, drugs, or other commodities (yes vs. no); experienced sexual violence (yes vs. no); experienced non-sexual violence, defined as being attacked, assaulted or suffering violence (yes vs. no). With the exception of demographic variables, self-reported being infected with an STI or HCV, and willingness and history of PrEP use, all variables referred to the six-month period before the interview. Many variable definitions have been used extensively and are identical to previous publications (Hadland et al., 2011; Kerr et al., 2009). In this study, non-answers (NAs) were excluded.

As a first step in the analysis, we evaluated the bivariate association between each explanatory variable and the outcome of interest, willingness to use microbicides, using logistic regression. To minimize estimation bias and assess the independent contribution of each variable, covariates with p-values below 0.10 in bivariate analyses were entered into a multivariable logistic regression model for adjustment. Variance inflation factor (VIF) values were calculated to assess the presence of multicollinearity among the variables included in the multivariable model, and the results indicated no evidence of multicollinearity. Characteristics of the study sample were summarized, stratified by willingness to use microbicides. Pearson’s χ² test was used for categorical variables, and the Mann–Whitney U test was applied for continuous variables. All statistical analyses were performed using R (Version 4.2.2, R Foundation for Statistical Computing, Vienna, Austria). All p-values are two-sided.

RESULTS

Between June 2021 and May 2022, 216 female sexually active participants were interviewed and were eligible for the present analysis. Among these individuals, the median age was 36 years old (interquartile range: 30–44 years old) and 102 (46.3%) identified as Black, Indigenous, or a Person of Colour. Only 32 (14.8%) participants indicated they were aware of microbicides in the context of HIV prevention, and 57 (26.4%) indicated a willingness to use a vaginal ring containing microbicides once it was described to them.

Characteristics of the study sample stratified by willingness to use microbicides and results of the bivariable analyses are reported in Table 1. Factors significant in the bivariable analyses included, experiencing homelessness (odds ratio [OR] = 2.69 [95% confidence interval [CI]]: 1.13–6.40); any injection drug use (OR = 1.93; 95% CI: 1.04–3.57); receipt of prescribed alternatives to unregulated drugs (OR = 3.40; 95% CI: 1.75–6.62); willingness to use PrEP (OR = 13.21; 95% CI: 6.41–27.19); engaged in sex work (OR = 3.31; 95% CI: 1.69–6.47); and experienced sexual violence (OR = 3.62; 95% CI: 1.06–12.38). In the multivariable analysis (Table 2), receipt of prescribed alternatives to unregulated drugs (adjusted odds ratio [AOR] = 3.30; 95% CI: 1.19–9.15); willingness to take PrEP (AOR = 14.87; 95% CI: 6.38–34.65); and engagement in sex work (AOR = 2.92; 95% CI: 1.19–7.15), were all independently and significantly associated with willingness to use microbicides.

Table 1.

Descriptive and bivariate analyses of factors associated with willingness to use microbicides among sexually active female PWUD in Vancouver, Canada (n = 216).

Characteristic	Yes n (%) (n = 57)	No n (%) (n = 159)	Odds ratio (95% CI)	p-value
Age
> 35	38 (66.7)	81 (50.9)	0.52 (0.28–0.98)	0.042
≤ 35	19 (33.3)	78 (49.1)
Race/Ancestry
BIPOC	32 (56.1)	70 (44.0)	0.61 (0.33–1.13)	0.117
White	25 (43.9)	89 (56.0)
Homelessness †
yes	11 (19.3)	13 (8.2)	2.69 (1.13–6.40)	0.026
no	46 (80.7)	146 (91.8)
Employment †
yes	17 (29.8)	67 (42.1)	0.58 (0.30–1.12)	0.104
no	40 (70.2)	92 (57.9)
Self-identified 2SLGBT identity
2SLGBT	17 (29.8)	44 (27.7)	1.11 (0.57–2.16)	0.757
Heterosexual	40 (70.2)	115 (72.3)
Any injection drug use †
yes	34 (59.6)	69 (43.4)	1.93 (1.04– 3.57)	0.036
no	23 (40.4)	90 (56.6)
≥ Weekly cocaine use †
yes	3 (5.3)	8 (5.0)	1.05 (0.27–4.10)	0.946
no	54 (94.7)	151 (95.0)
≥ Weekly crack cocaine use †
yes	9 (15.8)	25 (15.7)	1.00 (0.44–2.31)	0.991
no	48 (84.2)	134 (84.3)
≥ Weekly heroin/fentanyl/unspecified down use †
yes	3 (5.3)	2 (1.3)	4.36 (0.71–26.80)	0.112
no	54 (94.7)	157 (98.7)
≥ Weekly crystal meth use †
yes	24 (42.1)	53 (33.3)	1.45 (0.78–2.71)	0.237
no	33 (57.9)	106 (66.7)
≥ Weekly non-medical prescription opioid use †
yes	2 (3.5)	7 (4.4)	0.79 (0.16–3.92)	0.773
no	55 (96.5)	152 (95.6)
Drug/alcohol treatment †
yes	7 (12.3)	30 (18.9)	0.60 (0.23–1.39)	0.261
no	50 (87.7)	129 (81.1)
Prescribed safer supply †
yes	24 (42.1)	28 (17.6)	3.40 (1.75–6.62)	<0.001
no	33 (57.9)	131 (82.4)
Sex with men †
yes	31 (54.4)	102 (64.2)	0.67 (0.36–1.23)	0.195
no	26 (45.6)	57 (35.8)
Unprotected sex †
yes	28 (49.1)	91 (57.2)	0.72 (0.39–1.32)	0.292
no	29 (50.9)	68 (42.8)
Ever had STI
yes	41 (71.9)	92 (57.9)	1.87 (0.97–3.60)	0.063
no	16 (28.1)	67 (42.1)
Non-fatal overdose †
yes	17 (29.8)	31 (19.5)	1.75 (0.88–3.50)	0.11
no	40 (70.2)	128 (80.5)
History taking PrEP
yes	2 (3.5)	3 (1.9)	1.89 (0.31–11.62)	0.492
no	55 (96.5)	156 (98.1)
Willingness to take PrEP
yes	43 (75.4)	30 (18.9)	13.21 (6.41–27.19)	<0.001
no	14 (24.6)	129 (81.1)
Sex work †
yes	23 (40.3)	27 (17.0)	3.31 (1.69–6.47)	<0.001
no	34 (59.7)	132 (83.0)
Experienced sexual violence †
yes	6 (10.5)	5 (3.1)	3.62 (1.06–12.38)	0.04
no	51 (89.5)	154 (96.9)
Experienced non-sexual violence †
yes	13 (22.8)	30 (18.9)	1.27 (0.61–2.65)	0.523
no	44 (77.2)	129 (81.1)

^†Activity in the last 6-month period prior to interview.

Table 2.

Multivariable analysis of factors associated with the willingness to take microbicides among sexually active female PWUD in Vancouver, Canada (n = 216).

Variable	Adjusted Odds Ratio (AOR)	95% Confidence Interval (CI)	p – value
Age
(≤ 35 vs. < 35)	0.68	(0.25 - 1.81)	0.435
Homelessness †
(yes vs. no)	1.50	(0.43–5.24)	0.524
Living in DTES †
(yes vs. no)	0.93	(0.39–2.22)	0.864
Injection drug use †
(yes vs. no)	0.61	(0.23–1.60)	0.315
Opioid agonist therapy †
(yes vs. no)	0.70	(0.26–1.88)	0.478
Prescribed safer supply †
(yes vs. no)	3.30	(1.19–9.15)	0.022
HCV positive
(yes vs. no)	1.44	(0.56–3.75)	0.451
Ever had STI
(yes vs. no)	2.37	(0.98–5.72)	0.055
Opioid withdrawal †
(yes vs. no)	1.06	(0.42–2.68)	0.907
Willingness to take PrEP †
(yes vs. no)	14.87	(6.38–34.65)	<0.001
Sex work †
(yes vs. no)	2.92	(1.19–7.15)	0.019
Experienced Sexual Violence †
(yes vs. no)	4.39	(0.86–22.38)	0.075

^†Activity in the last 6-month period prior to interview.

DISCUSSION

Overall, our findings indicate a low level of awareness of microbicides (14.8%) among our sample of people born female at birth who use unregulated drugs. After explaining what microbicides are, just over one-fourth of study participants indicated they would be willing to use a vaginal ring with microbicides to prevent the acquisition of HIV. Willingness to use microbicides was significantly associated with accessing prescribed alternatives to unregulated drugs, willingness to use PrEP, and recent engagement in sex work.

Our findings are distinct from previous research exploring microbicide awareness and acceptability among select populations. A study of 504 women in a rural Ghanian community found only 2% of participants were aware of microbicides, though 95% were willing to use a microbicide when it becomes available (Abdulai et al., 2012). Another study by Darroch and Frost (1999) surveying over 1,000 women in the U.S. found that 93% of all respondents said they would be interested in using a vaginal microbicide if they were at risk of contracting a sexually transmitted disease. Additionally, 80% of all women said that they would have been interested in using such a product at some time in the past had it been available (Darroch & Frost, 1999). However, a 2007 study found that the prevalence of willingness to use microbicides among the general population remained highly contingent on product characteristics (e.g., messiness) (Morrow, Fava, Rosen, Vargas, et al., 2007b). Observed variation in reported willingness to use microbicides may be attributable to factors such as differences in study populations, levels of prior awareness, perceived risk of HIV, and the framing or specificity of the hypothetical product presented in each study.

Similar to our study findings, previous research has found willingness to use microbicides to be associated with individual-level factors such as race, or ethnicity, contextual factors such as the status of an individual’s romantic relationships, and product related factors, such as historical use of HIV preventative methods, messiness, and ease of application (Morrow, Fava, Rosen, Christensen, et al., 2007a; Sinkkanen, 2011). Among the general population, women were found to have greater willingness to use microbicides if they had a greater frequency of condom use in the past, a history of spermicide use, and were involved in casual sexual relationships (Sinkkanen, 2011).

Low levels of awareness of microbicides observed in the current study setting may be partially attributable to the absence of availability of microbicides in the Canadian context, underscoring the importance of accessibility in shaping individuals’ knowledge of and attitudes toward innovative biomedical HIV prevention methods (Sun et al., 2022). When participants were educated about microbicides, just over a quarter expressed willingness to use a vaginal ring containing microbicides for HIV prevention. This shift in willingness following education may point to the role of information dissemination in influencing individuals’ attitudes and preferences regarding HIV prevention (Lachowsky et al., 2019; Medley et al., 2009; Ratnawati et al., 2024). Moreover, low perceived risk of contracting HIV and limited familiarity with microbicides, compounded by high levels of mistrust in the healthcare system and difficulty accessing health services, may also contribute to greater hesitancy to use microbicides among our study population. With robust awareness campaigns and access to microbicides, acceptance and uptake of these innovative tools may increase among the current study population.

Participants who had access to prescribed alternatives to unregulated drugs had three times higher odds of expressing willingness to use microbicides compared to participants not accessing this intervention. This finding is consistent with previous literature highlighting that healthcare access and engagement can positively influence individuals’ attitudes toward emerging biomedical interventions (Ivsins et al., 2020). Formal connections to the healthcare system have been identified as a factor that fosters trust and confidence among structurally marginalized populations and healthcare providers (Berg et al., 2009; Montgomery et al., 2010; Moskowitz et al., 2011). This trust may positively influence participants’ willingness to embrace novel strategies for reducing HIV risk. Further study is warranted to explore if engaging with key populations through novel interventions such as prescribed alternatives to unregulated drugs may play a role in promoting the adoption of innovative biomedical interventions to reduce HIV transmission among PWUD.

Our study also found that participants who were willing to take PrEP had an increased odds of being willing to use microbicides. This association suggests that individuals who are open to using one form of HIV prevention may be more inclined to explore and adopt other complementary prevention measures. Moreover, the positive correlation between willingness to use PrEP and microbicides may be attributed to one's perceived risk of infection (Han et al., 2019). Research has shown that willingness to use PrEP is higher among individuals in high incidence groups who are at increased risk of HIV compared to those with a low risk of HIV (Belludi et al., 2021; Sun et al., 2022). As microbicides offer protection against HIV, willingness to use PrEP may be a strong indicator to assess willingness to use microbicides. This significant association suggests a co-occurring attitude among individuals who are receptive to one form of HIV prevention, potentially indicating a broader willingness to adopt comprehensive prevention strategies. Importantly, PrEP and vaginal microbicides would be considered to be complementary strategies as part of a combined HIV prevention approach, rather than replacements for one another (McNicholl, 2016). Given that they offer different mechanisms of action, delivery methods, and overall efficacy in preventing HIV acquisition, which can cater to diverse individual needs and offer potentially enhanced protection when combined (McNicholl, 2016).

Lastly, our study found that participants who recently engaged in sex work were more likely to report willingness to use microbicides. This finding is particularly significant given that sex workers face elevated risks of acquiring HIV and other sexually transmitted infections (Browne et al., 2023; Morrison-Beedy & Passmore, 2015b). Their heightened vulnerability results from various factors, including criminalisation (De Beck et al., 2017), increased numbers of sexual partners (Blower & Boe, 1993; Harrison et al., 2008), unprotected sexual acts (Blackard & Mayer, 2004), and social prejudice (Herek & Capitanio, 1999; Rhodes et al., 2005; Zierler & Krieger, 1997). This finding is consistent with other studies investigating willingness to use microbicides among the general population which found that having “non-main” sexual partners was associated with a greater willingness to use microbicides (Morrow, Fava, Rosen, Vargas, et al., 2007b). Non-main sexual partners were defined as “casual” partners who “you know, such as a friend, but [who you] are not in a committed relationship with,” or “other” partners whereby you do not know them (e.g., client, one-night sex, etc.) (Morrow, Fava, Rosen, Vargas, et al., 2007b). Another study investigating willingness among college-aged women found that woman in casual relationships and women with multiple sexual partners were both more likely to report being willing to use microbicides (Sinkkanen, 2011). Altogether, these findings suggest that willingness to use microbicides is likely associated with perceived risk of being exposed to HIV.

Overall, our study observed that women who use drugs who were willing to use PrEP, accessed prescribed alternatives to unregulated drugs, and/or engaged in sex work had an increased odds of reporting willingness to use microbicides. This convergence of findings is noteworthy as it suggests that certain key determinants of microbicide willingness may hold true across different populations. Recognising these commonalities can inform the development of targeted interventions and strategies aimed at promoting microbicide acceptability and uptake among diverse groups.

Our study has limitations. First, the data derived for this study is from a non-random sample, which limits the generalisability of our findings to other populations or regions. Second, the observational cross-sectional nature of the data restricts our ability to establish causation. Third, the use of self-reported data may introduce reporting biases, and social desirability bias could influence participants’ responses; however, previous research has determined that self-reported drug use behaviours are valid and reliable (Darke, 1998). Fourth, though social desirability bias might result in over-reporting of willingness, a previous study exploring the validity of reporting willingness to use a supervised injecting facility found that willingness measures are good predictors of later behaviour among this population (De Beck et al., 2012). Fourth, our main outcome variable, willingness to use microbicides, is inherently hypothetical, as microbicides are not currently available in Canada. Therefore, participant responses reflect attitudes based on a brief description of core product characteristics (ring form, localized mechanism, mild side effects). Although more detailed information about efficacy, product characteristics, or potential side effects may influence willingness, the concise description provided was intended to capture general acceptability of the concept of a vaginal microbicide ring among this study population, rather than detailed product-specific preferences. Fifth, in the multivariable modelling, large confidence intervals, particularly for the covariate “willingness to use PrEP” likely reflect sparse data in small subgroups; therefore, estimates should be interpreted cautiously. Finally, the COVID-19 pandemic may have affected the composition of our study sample. Participants without access to phones or the internet, as well as those who typically relied on in-person visits to the study office or received follow-up reminders through community services, may have been less likely to participate due to service closures and restrictions in place at the time of data collection. Consequently, it is possible that the levels of awareness and willingness to use microbicides do not accurately capture a more structurally marginalized group of PWUD. Nevertheless, we took a number of steps to reduce the possible influence of this selection bias, including loaning participants mobile phones to complete remote study assessments.

In conclusion, in the present study, we observed that over one-fourth of people assigned female at birth who use unregulated drugs surveyed would be willing to use microbicides. Willingness was positively associated with a range of factors related to substance use and HIV vulnerability in this study setting. Given the considerable proportion of participants who indicated reluctance towards the use of microbicides, additional research is warranted to characterize reasons behind the high levels of observed resistance. Further investigation should aim to understand factors contributing to sustained unwillingness and explore potential modifications to enhance overall levels of willingness. The relatively low level of willingness to use microbicides found in the current study population highlights the importance of continuing to support broader policies and interventions to effectively address HIV risk among women who use drugs. While emerging biomedical interventions, like microbicides, offer important opportunities for prevention, comprehensive approaches that consider social, structural and individual factors remain necessary to support individuals facing intersecting challenges related to substance use and HIV vulnerability.