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A growing body of evidence tells us that oral pre-exposure prophylaxis (PrEP) is a highly effective strategy for reducing the risk of HIV transmission when used consistently and correctly. In February 2016, Health Canada approved the daily use of the drug Truvada as PrEP, in combination with safer sex practices, to reduce the risk of sexual HIV transmission for people at high risk of HIV infection. This approval was a necessary step towards increasing access to PrEP in Canada. However, for PrEP to have an impact on preventing new HIV infections, it needs to be available to and used by people who are at high risk of getting HIV. Canadian service providers have a role to play in facilitating awareness, access and use of this HIV prevention tool.
This article will review research related to PrEP in the Canadian context and what we know about awareness, acceptability and uptake of PrEP in Canada.
PrEP effectiveness research and Canadian contributions
The effectiveness of daily oral PrEP has been demonstrated in multiple randomized controlled trials (RCTs) in countries other than Canada. Overall, the effectiveness of daily PrEP at reducing the risk of sexual HIV transmission ranged from zero to 86% in studies conducted among gay men and other men who have sex with men (MSM) and heterosexual men and women.1,2,3,4,5,6 The reason for this wide disparity is that not everyone was taking PrEP consistently. To demonstrate the importance of adherence, additional analyses in these trials looked at drug levels in the blood as a measure of who was taking PrEP consistently and who was not. These analyses found that daily PrEP reduced the risk of sexual HIV transmission by between 85% and 92% among participants who took the drug consistently compared to those who did not. One RCT has evaluated the use of daily oral tenofovir as PrEP in people who inject drugs. This study found that PrEP reduced the risk of HIV transmission by 49% overall, and by 84% among people who took PrEP consistently compared to those who did not.7,8
Canada has contributed to our knowledge of the rare circumstances in which HIV can be transmitted even when PrEP is used consistently and correctly. There have been two well-documented cases of HIV infection in people taking daily PrEP.9,10 The first reported case was a gay man from Toronto, who was adherent to PrEP for two years but became infected with a strain of HIV that was resistant to multiple antiretroviral drugs, including both of the drugs in Truvada.9 Although this type of resistance is rare, this case has been an important addition to international PrEP research because it highlights that transmission can occur even when PrEP is being used consistently and correctly.
Canada has also contributed to our knowledge of intermittent oral PrEP, taken “on-demand” for sexual HIV exposures. This strategy involves taking two pills before sex followed by one pill every day until two days after the last sexual event. The IPERGAY trial, which demonstrated the effectiveness of intermittent PrEP, included 400 gay men and other MSM in France and Montreal.11 The Montreal site enrolled 43 participants (11% of the total sample). The first phase of IPERGAY was a randomized trial, which found an 86% reduced risk of HIV infection among gay men taking intermittent PrEP compared to men taking a placebo (two participants in the PrEP group became infected compared to 14 in the placebo group). Adherence analyses showed that, overall, men in this study were having sex frequently, and taking an average of four pills per week. The trial continued as an open-label extension with all participants offered intermittent PrEP, and one further HIV infection occurred among 362 participants in the open-label extension.12 None of the three participants who became infected over the course of the entire study had PrEP drugs detected in their blood, which means they were not actually taking PrEP consistently. The results from this study are important because they demonstrate that an intermittent PrEP strategy can be considered for use by MSM to reduce the risk of HIV transmission.
Are priority populations aware of PrEP?
Awareness of PrEP among high-risk communities is varied.13,14,15,16,17,18 Increasing PrEP uptake among those at highest risk of HIV transmission requires that they know about it and want to use it. The majority of Canadian research about awareness and willingness to use PrEP has been conducted in gay men and other MSM, with few studies looking at other at-risk populations.
Research has found varying levels of PrEP awareness among MSM in Canada,13 but awareness appears to be increasing over time. For example, surveys conducted among MSM presenting for anonymous HIV testing in Toronto showed that awareness of PrEP has been steadily increasing. The proportion of MSM aware of PrEP in this population has increased from 14% in 201014 to 72% in 2015.15 However, levels of awareness seem to vary across the country. Research conducted in Vancouver from 2012 to 2014 found that only 21% of HIV-negative MSM were aware of PrEP,16 and a recent survey of MSM in Ottawa17 found that 53% knew about it.
Other priority populations may be much less aware of PrEP as an HIV prevention option. In a 2013 survey of people who inject drugs in Vancouver, only 3% knew about PrEP.18 Similarly, service providers working with African, Caribbean and Black (ACB) communities have reported low levels of PrEP awareness in their communities.19 Some attribute this to stigma around HIV leading to limited knowledge about HIV prevention in general in ACB communities.19
Perceived risk of HIV and willingness to take PrEP may impact uptake among at-risk populations
Despite growing awareness of PrEP among MSM in particular, increasing PrEP uptake among high-risk MSM may be challenging if they do not see themselves at high risk of HIV transmission or if they are unwilling to use it.
A study among MSM presenting for HIV testing at a Toronto sexual health clinic15 tried to identify the proportion of “optimal” MSM PrEP candidates. This study defined an “optimal” candidate as one who:
is at objectively high risk for HIV based on self-reported risk behaviours (using an HIV-risk screening tool)
perceives themselves to be at moderate-to-high risk, and
is willing to use PrEP.
Between November 2014 and April 2015, 64% of 420 MSM were found to be at objectively high risk, 53% were willing to use PrEP, and 27% perceived they were at moderate to high risk of acquiring HIV. Only 16% were determined to be “optimal” PrEP candidates.
This study shows that increasing the uptake of PrEP among high-risk MSM may be challenging because many MSM either do not think they are at high risk of HIV transmission or are unwilling to take PrEP. Among men who were assessed to be at high risk for HIV (those likely to benefit from PrEP), 68% did not perceive themselves to be at high risk, and 40% said they were not willing to use PrEP.
Encouragingly, Canadian research suggests that MSM with a higher risk of HIV transmission may be more willing to use PrEP.15,20,21 Another Toronto study of HIV-negative MSM, surveyed between September 2010 and June 2012, found that 55% were willing to take PrEP. Willingness to use PrEP was associated with sexual risk behaviours, such as condomless anal sex with casual partners.20 A study in Montreal found that over half of MSM presenting for rapid HIV testing at a Montreal clinic between July 2012 and November 2013 were interested in taking PrEP. In this study, willingness to take PrEP was associated with high-risk behaviours, such as having more than 10 sex partners in the previous three months.21
A 2013 survey of HIV-negative people who inject drugs in Vancouver found that only one-third were willing to use PrEP if it were made available.18 Willingness to use PrEP in this population was associated with increased risk, such as requiring help injecting, engaging in sex work, and reporting multiple sex partners.
Canadian research has identified concerns that may lower willingness to take PrEP. For MSM this includes concerns about possible drug side effects, cost, adherence to daily pill-taking, lack of a family physician, or discomfort talking to a medical provider about sexual health.13,15,20 Research with people who inject drugs has identified concerns about PrEP side effects.18
What do we know about PrEP delivery and use in the Canadian context?
Canadian demonstration and research projects support findings from similar projects in the U.S. and other parts of the world – notably, that adherence to PrEP is high, HIV infections are rare, and that MSM presenting for PrEP are likely to be at high risk for HIV, based on behavioural risk factors.
Canada’s first PrEP demonstration project, PREPARATORY-5, in Toronto, began enrollment in October 2014 and was ongoing when interim results were reported in May 2016. This study is following 52 MSM taking daily oral PrEP for one year. Preliminary results demonstrated very high adherence to daily PrEP, minimal increase in high-risk behaviours, and no HIV infections.22 This study enrolled MSM who reported condomless anal sex in the past six months, and who appeared to be at high risk for acquiring HIV based on their score using a validated HIV-risk screening tool. The high rates of sexually transmitted infections (STIs) that occurred during follow-up (46% of men were diagnosed with at least one STI) suggest that participants are continuing to participate in high-risk behaviours while taking PrEP.
Two other clinics with a large number of PrEP clients have also reported their findings. The Toronto HIV Prevention Clinic reported data from patients who were referred to the clinic for PrEP between January 2013 and April 2015.23 Of the 64 men who were referred, 45 (70%) went on to take PrEP, all of whom were MSM deemed to be at high risk for HIV. Most of the men who did not initiate PrEP reported low-risk sexual exposures; however, two men could not initiate PrEP because they were diagnosed with HIV at their intake visit. Although the average length of PrEP use among the men was only three and a half months, they had high adherence to follow-up clinic visits, and no HIV infections occurred over 13 person-years of follow-up.
Clinique L’Actuel in Montreal conducted a chart review of 355 patients who were taking PrEP. The average time on PrEP was six and a half months. The clinic reported no HIV infections and high adherence to PrEP since starting to prescribe PrEP in 2011.24 High-risk behaviours such as condomless anal sex did not increase significantly after starting PrEP. Data from this clinic support that MSM presenting for PrEP are already participating in high-risk sexual behaviours. For example, 80% had a history of STIs, 73% had more than 10 sex partners in the past year, and about half reported not using condoms consistently for anal sex.
All these studies saw high rates of STI diagnoses during study follow-up, which highlights the importance of regular STI testing while using PrEP. Additionally, high rates of baseline and incident STIs can indicate the presence of ongoing high-risk behaviours, such as condomless sex.
In addition to a history of STI diagnoses, previous or recurrent use of post-exposure prophylaxis (PEP) has also been identified in Canadian studies as a marker of ongoing risk for HIV.25,26 Factors such as these may be useful for helping to identify and prioritize people who may benefit from the use of PrEP.
Perceptions and practices of service providers
Increasing access to PrEP depends on awareness and acceptance of PrEP as a safe and effective HIV prevention option among a variety of health service providers. Several studies have looked at the opinions and practices, regarding PrEP, of various types of health and HIV-related service providers in Canada. Surveys have been conducted among Canadian physicians who would be likely to provide PrEP (including infectious disease specialists), pharmacists with experience in HIV care, and service providers from AIDS service organizations (ASOs) and community-based organizations (CBOs) working with MSM and ACB populations.
Much of the research on perceptions of service providers was conducted before Health Canada approved Truvada for PrEP and when we had limited data on the efficacy of PrEP. Since then, more research has been published, which shows that PrEP is very effective with good adherence.
In general, a majority of health service providers said that they support the use of PrEP for patients at high risk for HIV. Surveys in physicians, HIV pharmacists, and frontline ASO workers found that about half believed that PrEP should be approved.27,28,29 In 2012/13, more than two-thirds of pharmacists surveyed said they would provide education in support of PrEP use.27 Only 45% of physicians surveyed around the same time said they would be willing to prescribe PrEP.28Physicians who were familiar with PrEP or who had been asked about PrEP by a patient were more likely to be willing to prescribe it, suggesting that willingness to prescribe PrEP may increase as more clinicians and patients become aware of PrEP as an effective HIV prevention tool.
The most common concerns about PrEP from all health service providers included: cost and accessibility, adherence, drug resistance, drug toxicity, and efficacy in a real-world setting.13,19,27,28,29 Front-line service providers working with priority populations (ACB and MSM communities) identified additional concerns related to gender-based inequities in access to PrEP, the lack of consensus and guidance in PrEP messaging, and the ethics of increasing access to antiretroviral drugs for preventing HIV, while many people living with HIV lack access to treatment.13,19
Lack of education and knowledge about PrEP among clinical service providers was identified as a major barrier since, at the time the research was conducted, many did not feel prepared to discuss PrEP with patients.27,28 Since PrEP is only available by prescription, clinicians in particular need to have sufficient knowledge about PrEP to feel comfortable prescribing it to their patients.
Cost as a barrier to PrEP access
A major barrier to accessing PrEP is the cost. A month-long course of daily PrEP can cost between $800 and $1000. People considering using PrEP may need support in determining whether their provincial/territorial or private health insurance will cover the cost of the medications or if supplementary private insurance coverage can be purchased. Currently, PrEP coverage is available through Quebec’s public drug plan and for First Nations and Inuit people under the Federal Non-Insured Health Benefits (FNIHB) drug formulary.
In August 2016, the Canadian Drug Expert Committee (CDEC) of the Canadian Agency for Drugs and Technologies in Health (CADTH) recommended that the cost of Truvada, used as oral PrEP to reduce the risk of HIV infection, should be reimbursed by public drug plans in Canada. The CDEC specified that Truvada be reimbursed provided that PrEP is:
prescribed within the context of a sexual health program, by a prescriber experienced in the treatment and prevention of HIV, and
available at a lower price.
This recommendation was based on evidence regarding the effectiveness, safety, and cost-effectiveness of PrEP. The CDEC also considered patient input that was collected by three organizations representing potential patient groups (Maggie’s: The Toronto Sex Workers Action Project; the Canadian Treatment Action Council; and the AIDS Committee of Toronto). The CDEC recommendation is considered by each provincial, territorial, and federal drug plan when deciding whether or not to cover the cost of a drug, and when negotiating the price of a drug. A positive recommendation does not guarantee that PrEP will be covered by any public plans. Provinces must now decide whether to cover Truvada for PrEP under their drug plans and how they will cover the cost.
Upcoming initiatives to improve access to and delivery of PrEP
There are several projects underway to facilitate access to PrEP by increasing PrEP-related knowledge and capacity among medical providers and potential PrEP users in Canada. In March 2016 a group of stakeholders, including people living with HIV, researchers, and representatives from organizations working in HIV, met to develop recommendations to support the scale-up of PrEP implementation in Canada.30Priority directions for ongoing research and evaluation include:
Development of a national database to monitor people on PrEP.
Cost-effectiveness modelling, to estimate the benefits and costs of implementing PrEP on a larger scale.
Development of national guidelines and educational resources.
Scale-up of PrEP implementation projects that have begun in MSM across the country.
Development of demonstration projects in other at-risk communities.
The work on cost-effectiveness modelling has already begun. A PrEP modelling study based on Toronto MSM estimated that targeting PrEP delivery to the highest risk MSM, and providing adherence support to maximize efficacy, is the most cost-effective PrEP implementation strategy in Toronto’s context.31
The CIHR Canadian HIV Trials Network (CTN) is leading the development by a group of clinicians, researchers and community members of national guidelines for the prescribing of PrEP and PEP in Canada. These guidelines will provide evidence-informed guidance on how to assess patient eligibility for PrEP and how to correctly prescribe it. The guidelines are expected to be released in early 2017.
Other educational and training resources are also being developed to support physicians to deliver PrEP. As part of a research project, a group of clinicians and researchers is developing a continuing medical education (CME) course for physicians in Canada to learn more about PrEP effectiveness, safety, and how to prescribe it and provide follow-up care. Various communications approaches will be used to promote the course. One novel approach is that the researchers will engage with high-risk MSM and support them to initiate a conversation about PrEP with their doctor, who could then complete the CME course.
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About the author: Camille Arkell is CATIE’s Knowledge Specialist, Biomedical Science of Prevention. She has a Master’s of Public Health degree in Health Promotion from the University of Toronto, and has been working in HIV education and research since 2010.
This article by Camille Arkell previously appeared at CATIE, here.
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