Awareness of,usage of and willingness to use HIV pre-exposure prophylaxis among men in downtown Toronto,Canada

INTRODUCTION

Pre-exposure prophylaxis (PrEP) is a promising strategy in which HIV-uninfected people could take antiretroviral (ARV) medications on a regular basis to reduce their risk of acquiring HIV. ^1,2 Groundbreaking results from the recently reported Pre-exposure Prophylaxis Initiative (iPrEx) trial demonstrate that PrEP using daily oral tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) can achieve a 44% reduction in HIV acquisition (95% confidence interval [CI], 15–63) among high-risk men who have sex with men (MSM) and transgender women. ³ Even in advance of that report, however, lay media had suggested that PrEP was being used in an unsupervised and/or off-label fashion by MSM in some large American cities despite unconfirmed efficacy and safety. ^4–6 However, scientific literature on the topic has not confirmed such use; knowledge of PrEP has generally been found to be limited, while usage was rare. ^7–9 In the rare instances where individuals had used PrEP, they reported obtaining it from HIV-infected friends or partners, health-care providers or drug dealers. ⁹

Reassuringly, more recent data on the safety of daily TDF-based PrEP in MSM showed no significant safety concerns. ¹⁰ However, unregulated PrEP usage has the potential to yield harmful effects such as increased and/or riskier sexual behaviour, unmonitored drug toxicities, unintended drug exposure for hepatitis B infection and increased ARV drug resistance at both the individual and community levels. ^11–13 Continued use of a PrEP regimen in the presence of undiagnosed HIV infection is analogous to the HIV monotherapy or dual therapy strategies used in the early stages of the HIV epidemic. Such regimens are known to carry an unacceptably high risk of HIV drug resistance, with important clinical implications for the patient himself and public health implications for his sexual partners. ¹¹ Indeed, in the iPrEx trial, the two participants in the intervention arm who were HIV-infected at enrolment were found to have FTC-resistant virus, while neither had TDF resistance; none of the 36 participants who became HIV infected during the trial had FTC- or TDF-resistant infections, although adherence to study medications was limited. ³

To assess current levels of awareness and usage of PrEP in Toronto, Canada, we surveyed high-risk men at a popular sexual health clinic. We also examined this population's willingness to use PrEP in the future. Data collection for this study was completed several months before publication of the iPrEx trial results. To our knowledge, ours is the first study evaluating pre-iPrEx trial knowledge and usage of PrEP in Canada.

METHODS

Men undergoing a rapid HIV test from February–July 2010 at the Hassle Free Clinic, a publicly-funded sexual health clinic serving a large MSM population in downtown Toronto, were eligible to participate. Transgender individuals identifying themselves as men were also eligible. Exclusion criteria were an inability to understand the English language questionnaire or receipt of a reactive HIV test, since it was deemed inappropriate to request completion of a questionnaire under these circumstances. The clinic staff administering the point-of-care HIV test provided participants with a letter of information describing the study prior to providing the questionnaire. Questionnaires were self-administered in a private room and returned in a sealed envelope to the clinic reception. Informed consent was inferred by questionnaire completion as stated by the letter of information.

The anonymous questionnaire included 20 items about demographics, sexual partners, substance use, as well as awareness of, usage of and willingness to use PrEP. Questions were worded to emphasize to participants that they were being asked about PrEP, rather than postexposure prophylaxis (PEP). For example, italics and boldface font were used in the question ‘Have you ever heard of taking HIV medications before sex to try to prevent HIV infection?’

Participant characteristics were analysed using descriptive statistics. The primary outcome was the proportion of MSM respondents reporting use of PrEP. Participants reporting any male partners (exclusively or in addition to female or transsexual partners) were classified as MSM. While MSM were the primary population of interest for this study and for future PrEP use, non-MSM were also included in the study because their decision to undergo a rapid HIV test implied possible high-risk exposure, and because we wished to compare knowledge, usage and willingness to use PrEP in MSM and non-MSM populations. Using a low expected PrEP use prevalence of roughly 2% and a desired precision of 2% for the 95% CI around this point estimate (i.e. from 0 to 4%), a sample size calculation determined that at least 189 MSM would be needed, under the normal approximation assumption.

Logistic regression models were used to identify variables associated with awareness of and usage of PrEP using forward selection. In exploratory analyses, responses regarding willingness to use PrEP if proven safe and effective were collapsed from a four-level response variable (‘definitely’, ‘maybe’, ‘no’ or ‘unsure’) into a dichotomous variable (‘definitely or maybe’ versus ‘no or unsure’), and logistic regression models were used to identify variables associated with willingness to use PrEP.

Ethical approval for this study was obtained from the St Michael's Hospital Research Ethics Board prior to the initiation of any study activities.

RESULTS

Responses regarding participants’ willingness to use PrEP if proven to be safe and effective are shown in Table 1. In univariate, exploratory logistic regression models, variables associated with ‘definitely’ or ‘maybe’ being willing to use PrEP included MSM status (OR = 1.90, 95% CI: 1.06, 3.41), more than one sexual partner in the preceding six months (OR = 2.43, 95% CI: 1.27, 4.66 for those with 2–4 partners; OR = 2.11, 95% CI: 1.08, 4.10 for those with 5 or more partners) and unprotected anal sex in the past six months (OR = 2.02, 95% CI: 1.19, 3.42). Unprotected anal sex under the influence of alcohol in the past six months (OR = 2.44, 95% CI: 1.24, 4.81) was also associated with willingness to use PrEP, while unprotected anal sex under the influence of drugs was not, likely due to the small proportion of respondents reporting that risk activity. In the multivariate model, only the number of sexual partners was statistically significantly associated with willingness to use PrEP, with a trend towards an effect observed with unprotected anal sex.

DISCUSSION

We found low levels of PrEP awareness among HIV-uninfected men seeking non-nominal, point-of-care HIV testing in Toronto. Roughly 5% of non-MSM and 14% of MSM were aware of PrEP; this latter prevalence is similar to that found by studies among MSM in the USA. ^7–9 Reassuringly, we found no evidence of PrEP use in this sample during a time period when no data showing proof of PrEP safety and efficacy among MSM were yet available. While previous studies in the USA did find some off-label PrEP use, it was very rare (<1%), and most reports originate in cities where PrEP research was ongoing within the local MSM community.

Considering such ARV use has the potential for negative health consequences at both the individual and public health levels, PrEP usage should continue to be monitored, particularly in the MSM population, where awareness of PrEP appears greatest and is likely to increase in the wake of the iPrEx findings. Specifically, there is concern that new HIV prevention technologies may result in increased sexual risk-taking (‘risk compensation’), resulting in higher rates of sexually transmitted infections. ^11,13,14 Although carefully conducted clinical trials and observational studies have thus far failed to document this effect, ^10,15,16 findings obtained in these contexts may differ from real world settings. Further, TDF/FTC is associated with short- and long-term toxicities that warrant clinical monitoring, including gastrointestinal intolerance, renal tubulopathy, decreased creatinine clearance and decreased bone mineral density, although further research regarding the clinical significance and optimal monitoring strategies for the latter is still needed. ^17–20 Finally, unregulated PrEP using TDF/FTC in the context of prevalent or incident undiagnosed HIV and hepatitis B infections would be expected to drive drug resistance at both the individual and community levels, particularly given the low genetic barrier to resistance of FTC in both viruses, ¹¹ and could cause clinical flares of hepatitis. ²¹

Willingness to consider PrEP use was high in our sample, particularly in the MSM population, and appeared to be associated with higher risk activities such as greater numbers of sexual partners and unprotected anal sex. These preliminary findings are encouraging because if future clinical trials confirm PrEP to be efficacious and safe, it is most likely to be considered for those engaging in higher risk activities. However, determining whether, where, when and how to optimally roll out PrEP will require a multistakeholder process to ensure that optimal strategies for financing, administering and monitoring this promising new HIV prevention strategy are developed.