Exploring new Doxy-PEP guidelines

This transcript is the automated English captions in the recordings. The text may not align with the audio and there may be errors the transcript.

Jessica Helwig: Hello everyone. my name is Jessica Helwig and I am a senior policy analyst with the public health agency of Canada. Thank you for joining to today's communicable disease in infection control webinar series. 

We are pleased to have you join us for today's event. As we come together in this virtual space, I wish to recognize the importance of the lands on which we each find ourselves. From coast to coast to coast, we acknowledge we are on the traditional lands of First Nations, Inuit, and Metis people. 

Today I am calling in from Ottawa, which is built on unsurrendered and unceded Anishinaabe Algonquin territory. A few notes for today's webinar. Following today's event, a copy of the presentation deck and a recording of the presentations as well as a feedback form will be sent to you. 

The webinar will be conducted in English. Simultaneous interpretation in French can be accessed through selecting the interpretation button in the menu at the bottom of your screen. Your audio has been muted to reduce noise and your video is disabled for today's webinar. 

If you are having technical problems and need help, please feel free to reach us through the chat function. You can communicate in either English or French. And if you have a question for one of our presenters, please submit your questions using the Q&A function where we will look to answer them during the panel discussion at the end of the webinar. 

Note, you may check send anonymously if you do not want your name attached to the questions. I will now introduce our speakers for today's webinars.  

Genevieve Gravel is an epidemiologist and the manager of the Sexually Transmitted Infections and Hepatitis Surveillance Section at PHAC. The team's mandate includes enhanced surveillance of syphilis and antimicrobial-resistant gonorrhea, as well as the analysis and dissemination of routine surveillance data for chlamydia, gonorrhea, syphilis, and hepatitis B and C. 

Dr. Andrea Chittle is a Medical Advisor in the Sexually Transmitted and Blood-borne Infections Surveillance Division at PHAC. Additionally, Andrea works in the City of Hamilton’s Sexual Health Clinics and is a Consultant Physician with the Sexual Assault and Domestic Violence Care and Treatment Centre at Guelph General Hospital. 

And with that, I will turn it over to today's presenters. 

Genevieve Gravel: Thank you. So, I'm going to take it from here. Sorry, I was trying not to go too fast either. 

so okay a few definitions and background information before we get started. so doxycycline postexposure prophylaxis or doxy-PEP involves taking a dose of antibiotic doxycycline following condomless oral anal or vaginal sex to prevent chlamydia, syphilis and possibly gonorrhea. doxycycline preexposure prophylaxis or doxy-PrEP involves taking the antibiotic doxycycline every day to prevent bacterial STI. 

Doxy-PEP and doxy-PrEP do not protect against HIV.  

So now STI epidemiology in Canada.  

So the purpose of epidemiologic monitoring and surveillance is to understand trends epidemic drivers, risk factors, identify priorities for action and track progress towards elimination targets. 

There are a variety of methods used. Routine surveillance of nationally notifiable STBBI is our main surveillance method. In Canada, there are six “traditional” STBBI that are notifiable : chlamydia, gonorrhea, syphilis, HIV, hepatitis B and hepatitis C. Mpox was added in 2024. Annually, provinces and territories voluntarily provide notifiable disease data to PHAC so that we can establish a national portrait.  

Routine surveillance data give us a good idea of general trends in reportable STBBI over time, and by age, sex, and province/territory. However, there is limited variable information provided on risk factors, race or ethnicity, or key population. 

We supplement the information from routine surveillance with other methods, such as enhanced surveillance and estimates. Enhanced surveillance systems collect additional variables on diagnosed cases of STBBI, sometimes through sentinel sites, or perhaps by doing surveys among key populations, such as the Tracks system. Mathematical modelling can be used to produce estimates of incidence, prevalence, and care cascade indicators, project future trends, or predict the outcomes of various proposed interventions. Mathematical modeling can be used to produce estimates of incidents, prevalence, and care cascade indicators, project future trends, or predict the outcomes of various proposed interventions.  

So, chlamydia now chlamydia is the most reported notifiable disease of all and the most reported bacterial STI by far. So, we have over 129,000 cases were reported in 2023 nationally. 

So, that's equivalent to a total rate of 323 per 100,000 population. The rate has been increasing since 1996 and from 2014 to 2023 the rate increased by 5% with a dip during the period of 2020 to 2023 the COVID-19 pandemic years. So this is shown on the gray zone on the left side graph. 

Rates of chlamydia reported in females are higher compared to males nationally and the gap between the sexes has been decreasing over time. As you can see when we look at rates by sex and age group in 2023 which is the graph on the right females 20 to 24 year old had the highest rate while among males it's the same age group that has the highest rate but we note that younger females are more affected than their male counterparts. Gonorrhea is the second most reported bacterial STI. 

The rate has been increasing since 1997 and more than doubled over the last 10 years. And as for chlamydia, we can see a dip during the COVID-19 pandemic years, but more so in the first years of the pandemic. 42,066 cases were reported in 2023 for a total rate of 104 per 100,000 population. 

In contrast to chlamydia, higher rates of gonorrhea are reported in males compared to females nationally. The rate among males is increasing faster, increasing the gap between the males and the females. So for each case actually among females, there are more than two cases among males reported. 

When we look at rates by sex and age group in 2023, male between the ages of 25 to 39 years at the highest gonorrhea rates and the next highest rates for males and females were among those between the ages of 20 and 24 years. Now syphilis or more precisely infectious syphilis on this figure in 2023 there were 12,135 cases of infectious syphilis reported nationally for a rate of 30.5 cases per 100,000 population. 

 So the 2023 national rate of infectious syphilis was actually 44 times at that of 2014. 

While a decrease is observed in 2023, it's too soon to tell if this downward trend will continue. Nationally, 64% of cases reported in 2023 occurred among males. in comparison, in 2018, 79% of cases occurred among males. 

And the rate among females tripled since 2018, a much faster increase than among the males, where it was 43%. The rise in rates of infectious syphilis among females of reproductive age have led to a reemergence of congenital syphilis in Canada. From data reported by eight provinces and territories, gay, bisexual, and other men who have sex with men, GBMSM, represented 27% of all reported infectious syphilis cases in 2023. 

for these provinces and territories. Cases among those not identified as GBMSM increased much faster compared to GBMSM cases since 2018. In 2023, males aged 30 to 39 years had the highest national rate of infectious syphilis of any age group and the rate were highest among the 25 to 39 years old for males and among the 20 to 29 year old for females. 

So as for chlamydia, younger females are more affected than their male counterparts. I'll now share some enhanced surveillance work on antimicrobial resistance in gonorrhea that has some relevance for the new doxycycline pep recommendations. Antimicrobial resistance or AMR in gonorrhea is a significant public health issue in Canada. 

Antimicrobial resistance in this area. Gonorrhea, the bacteria that causes gonorrhea is monitored through the lab-based gonococcal antimicrobial surveillance program or GASP Canada and the case-based enhanced surveillance of antimicrobial resistant gonorrhea system. So, ESAG links a subset of GASP Canada antimicrobial resistant gonorrhea data to epidemiologic and clinical data for an improved understanding of our trends across Canada. 

Between 2018 and 2023, close to 5,000 cases each having gonococcal sample cultured were reported to ESAG of which 45% were GBMSM shown in the dark blue on the figure. So doxycycline is a member of the tetracycline antibiotic class group. and resistance to the antibiotic the tetracycline one of the antibiotic in that class the tetracycline antibiotic class is monitored through GASP Canada and ESAG because tetracycline and doxycycline share resistance mechanisms. 

resistance to the antibiotic tetracycline data are used to make inferences about the likely effectiveness of doxy-PEP for preventing gonorrhea. Importantly use of doxy-PEP could create selection pressure favoring the survival of tetracine resistant strains and multi-drug resistant strains of gonorrhea and other bacteria. So monitoring resistance to tetracycline in gonorrhea and other bacteria can support our understanding of the impacts of doxy-pep intervention. 

The ESAG dashboard offers some data on gonorrhea tetracycline antibiotic resistance among GBMSM here compared to among heterosexual males. Note that the scales in the starting point on the y-axis differ and COVID-19 pandemic years make the trends difficult to interpret. However, the figures show that on average between 2018 to 2023 a greater proportion of cases are resistant to tetracycline antibiotic among GBMSM than among heterosexual males. 

So that's 54% versus 45% respectively. More years of data are necessary to determine the trend in the second resistance in those populations. But it will be interesting to follow this indicator in coming years along with the tetracycline resistance data from GASP among all the cases in Canada. 

More detailed data on gonorrhea antimicrobial resistance are available through health infobase GASP and ESAG dashboards which we provide the links to in the list of resources in annex. So now back to tracks. tracks is a biobehavioral enhanced surveillance initiative at PHAC focusing on key populations for a survey among the two spirit people gay, bisexual, queer and transmen and non-binary people or 2S/GBTQ+ people. 

PHAC and a community-based research center or CBRC collaborated in 2024. The study aimed to describe the prevalence of HIV and other STBBI and associated factors in this population. Local study teams actively recruited at venues by approaching potential participants. 

The self-administered questionnaire collected information on the sexual health and well-being of 2SGBTQ plus people. From the survey, we found that in the past 12 months, 5.6% 6% of participants self-reported having been diagnosed with gonorrhea, 5.2% with chlamydia, and 2.3% with syphilis. From the same survey, it appears that less than half of the participants were aware of Doxy-PrEP or PEP. 

that's shown in the dark teal in the column on the left. only 11% of the participants had ever taken doxy-PEP or PrEP represented in the dark teal again but that's in the middle column and finally on the column on the right among the participants who had not taken doxy-PEP or PrEP and or who were unsure whether they'd taken it about one third were interested in using it and that's shown in dark teal and while one-third were unsure if they would be interested in using that's in the sand color. So that sums it up for my part. 

the latest publications and resources on the epidemiology of STI are available in annex at the end of this presentation deck that we will share with attendees.  

I will pass the virtual microphone to Andrea and we will share the slide deck sharing.  

Andrea Chittle: Thanks Genevieve. 

Genevieve: I'm just setting up your things. 

Andrea: Yes. And so it looks like that has worked. 

Thanks, Genevieve, for letting me know. Perfect. 

So, Genevieve’s presentation highlighted epidemiologic trends that relate to the new national recommendations for doxycycline to prevent syphilis, chlamydia, and possibly gonorrhea. 

Before I get into the details of those recommendations, I want to provide a bit more background information. I'm going to start by sharing a depiction of the STBBI prevention toolbox. Then I'll review PHAC’s approach to developing recommendations for sexually transmitted and bloodborne infections and summarize the information that was considered as we developed the new doxy-PEP recommendations. 

I'll review the doxy-PEP recommendations and use a case example to highlight how doxy-PEP can be integrated into comprehensive STBBI care. And I want to mention that the use of doxycycline as prophylaxis against bacterial STI is an off label use of this drug. This means that Health Canada has not approved the use of doxycycline for this indication. 

I'd like to get a better understanding of everyone's familiarity with the range of sexually transmitted and bloodborne infection or STBBI prevention tools. A polling question should have popped up on your screen and I'll give a few moments for people to select their top choice. Okay, so it looked like about half of people who participated indicated that they're least familiar with biomedical interventions. 

And so for this presentation and PHAC guides, we're using the term biomedical interventions to describe a category of prevention tools that includes vaccinations and therapeutics that are used as pre and postexposure prophylaxis for HIV and bacterial STI. And I'm going to get into more detail about doxy-PEP in particular. And we'll share some resources about U=U as it relates to HIV prevention. 

This slide depicts the range of effective STBBI prevention methods as tools in a figurative toolbox. Broadly, prevention methods reduce the risk of acquiring sexually transmitted and bloodborne infections and or the impact and spread of sexually transmitted and bloodborne infections. While some tools like education and vaccination against hepatitis B virus HPV have broad use and benefit, others like harm reduction and vaccination against monkeypox virus MPOX are strategies that have particular relevance and benefit for certain individuals and communities. 

Generally, the prevention methods complement each other and comprehensive STBBI services will incorporate all relevant tools. And as I mentioned, I'm going to be highlighting some of the biomedical interventions, particularly doxy-PEP in this presentation. PHAC provides evidence-based public health guidance for the prevention and management of STBBI. 

This guidance is developed in collaboration with an expert advisory committee, the National Advisory Committee on Sexually Transmitted and Bloodborne Infections or NAC-STBBI. The NAC-STBBI consists of members from across Canada who have expertise in relevant public health and clinical areas including epidemiology, infectious diseases, primary care, obstetrics and gynecology, medical microbiology, and pharmacology. The figure on this slide summarizes the methodology for developing recommendations. 

Guideline development begins with a topic selection and prioritization exercise. Once a topic has been selected, a working group is formed. Working groups include members of the NAC-STBBI and may include external experts and stakeholders. 

PHAC provides methodological and technical support to working groups. A scoping exercise of the topic is conducted to support the working group in developing research questions and the inclusion and exclusion criteria. Specifically, the scoping exercise informs the identification of the population, intervention, comparison, and important outcomes relevant to the topic. 

The working group members rate the relative importance of outcomes for decision-making based on the grading of recommendations, assessment, development, and evaluation or grade approach. The scoping exercise also helps the working group determine whether a systematic review is necessary, whether to use and or update an existing systematic review, and whether to adopt, adapt or develop denovo recommendations for the topic. The evidence review protocol is developed, the evidence review undertaken, and the evidence is appraised, synthesized, and reviewed in a structured and transparent way by the working group to support the development of recommendations. 

The working group drafts recommendations using the grade wording for direction and strengths as appropriate. And these draft recommendations are presented to the full NAC-STBBI for discussion and voting. The recommendations are then finalized and summarized in a statement. 

The statement undergoes fact internal reviews and approvals and is then published to canada.ca and the STBBI guides are updated to incorporate the recommendations. The recommendations are then disseminated through activities like this webinar. You can find the NAC-STBBI's recommendations in fact STBBI guides for health professionals. 

This information is also available on a mobile app. There is often a lag between posting content to the online version of the guides and updating the content in the mobile app. for the Doxy-PEP recommendations. 

Updates are pending to the mobile app and I would recommend that people refer to the online guides at this time. Another polling question should pop up and this may be a question that you've seen before if you've attended other CDIC webinars. but I think it's an important point to emphasize. 

If there are discrepancies between provincial, territorial, or local guidelines and PHAC guidelines for STI care, clinicians should follow fact guidelines. Okay. And a pretty much an even split from part participants who answered that question. 

I think there's a bit of a double negative in there, so it might have been a bit of a trick question, but the answer is false. You should generally defer to local, provincial, or territorial recommendations if these are different from PHAC recommendations. And that's because local, provincial, and territorial recommendations consider important factors that are relevant to your context, including epidemiologic trends and antimicrobial resistance patterns. 

I'll spend the next few minutes and slides reviewing the development of the new doxy-PEP recommendations. In September 2023, the NAC-STBBI prioritized the development of recommendations on prophylactic doxycycline to prevent bacterial sexually transmitted infections. A working group was formed that included members of the NAC-STBBI and subject matter experts. 

An environmental scan of existing recommendations was undertaken to inform this work. This slide provides a high-level synthesis of the recommendations from other jurisdictions that the working group reviewed. Guidelines for the prophylactic use of doxycycline to prevent syphilis, chlamydia, and gonorrhea are emerging and recommendations continue to be updated and new ones published. 

This reflects that this is an active area of ongoing study and evidence is accumulating. A number of international organizations like the Australasian Society for HIV viral hepatitis and sexual health medicine have published guidance on the use of doxy-PEP for gay, bisexual and other men who have sex with men and transgender women at increased risk of bacterial sexually transmitted infections. Some organizations specify that Doxy-PEP's role is primarily for the prevention of syphilis. 

Existing recommendations consistently emphasize that doxy-PEP should be embedded within comprehensive STBBI services. The Belgian research HIV consortium published a statement in 2024 recommending that doxy-PEP use be limited to medically supervised settings and clinical studies. The published recommendations all contain guidance to council users of doxy-PEP about the unknown and potential impacts of doxy-PEP on the emergence and acceleration of antimicrobial resistance. 

Considering the environmental scan and initial evidence review, key questions were developed. Four of these questions were prioritized and the new recommendations answer the first of these questions which is should doxy-PEP or standard care be used in cisgender GBMSM and transgender women at risk of chlamydia gonorrhea or syphilis infection. The working group reviewed relevant evidence including clinical studies specifically evaluating doxy-PEP among cisgender GBMSM and transgender women as well as published clinical lab genomic and encilico data and published models. 

The clinical studies demonstrated that doxy-PEP administered as 200 mg orally 24 to 72 hours after condomless sex is highly efficacious for preventing chlamydia and syphilis over 12 to 18 months. Findings for gonorrhea varied between studies perhaps related to different baseline rates of tetracycline class antibiotic resistance in gonorrhea. The working group also reviewed results from models, including models that used the trial data to identify prescribing strategies, predict the duration of doxy-PEP's effectiveness for gonorrhea prevention, and project the impact of doxy-PEP on incident syphilis infections. 

The working group considered evidence on the antibiotic resistance consequences of the use of tetracycline class antibiotics broadly and of doxy-PEP in particular. The evidence reviewed indicates that the use of tetracycline class antibiotics including as doxy-PEP creates antibiotic selection pressure for gonorrhea. This can increase resistance to tetracyclines and other classes of antibiotics. 

It can also increase resistance to tetracycline and to other classes of antibiotics in commensal and pathogenic bacteria like Staphylococcus aureus. The working group also looked for relevant evidence about patient values and preferences, resource use, cost effectiveness, feasibility and acceptability, and equity. The working group determined that on balance, the known benefits of doxy-PEP for cisgender GBMSM and transgender women currently outweigh the potential harms. 

And they developed two recommendations for the use of this intervention. My colleagues I think have pasted a link in the chat to the executive summary document for these recommendations. Recommendation one focuses on offering doxy-PEP and recommendation two focuses on counseling. 

Each recommendation contains remarks for healthcare providers to explain the recommendation and to describe relevant considerations. Recommendation one is a conditional recommendation and is based on moderate certainty of evidence of effects for the effectiveness evidence. The NAC-STBBI suggests offering doxycycline postexposure prophylaxis as 200 mg orally taken within 72 hours of exposure to cisgender, gay, bisexual, and other men who have sex with men and transgender women at increased risk of bacterial STI as a component of comprehensive STBBI services to reduce the risk of syphilis, chlamydia, and possibly gonorrhea. 

As I mentioned, this is an off label use of doxycycline. 

Recommendation two is a strong recommendation based on moderate certainty of evidence to inform shared clinical decision-making about doxy-PEP use. The NAC-STBBI recommends discussing personal, community, and population level risks of antimicrobial resistance with individuals considering this intervention. 

I'll share additional details about the remarks when I review a case example. And that was a segue to the case example, which is the final section of the presentation. The case that I'm reviewing, Harris, is a fabricated case. 

Any similarities that you may notice between Harris and a real person are purely coincidental. Harris presents to care for asymptomatic sexually transmitted and bloodborne infection screening. He is a 28-year-old cisgender man. 

This means that Harris's assigned sex at birth was male and his gender identity is man. Harris uses the pronouns he him. He works as an accountant. 

His sexual partners are cisgender men and he has insertive and receptive anal and oral sex using condoms sometimes. Harris was in a long-term closed monogamous relationship, but it ended 3 months ago and in the last 2 months he has had five sexual partners. He most recently had condomless anal sex 2 weeks ago. 

He was last screened for sexually transmitted and bloodborne infections 1.5 years ago. Harris was treated for pharyngeal gonorrhea infection 2 years ago and for urethral chlamydia 3 years ago. He has no other notable past medical history. 

He's not taking any prescription medications and doesn't have any drug allergies. Another poll question should appear. In considering what I've shared about Harris, what other information would be important in counseling him about STBBI prevention? 

Would you be interested in knowing about his history of vaccination for hepatitis A, hepatitis B, HPV, and MPXV? his history of sharing drug use equipment, his history of unprofessional tattoos or piercings, or all of the above. Okay. 

And most people responded all of the above, which is correct. All of this information would be relevant to discussing comprehensive STBI prevention with Harris. So Harris shares that he completed vaccine series for hepatitis A, hepatitis B, and HPV. 

He received one dose of vaccine against MPOX in 2022. He discloses that he has shared bills when using inhaled substances, most recently one year ago, and he has not received any unprofessional tattoos or piercings. Returning to the STBBI prevention toolbox, several of the tools are relevant for Harris. 

I'll review the relevant tools, recognizing that covering everything in a single clinic visit is not practical in most settings. Education involves providing tailored information about STBBI risks and prevention. For Harris, it would be relevant to mention harm reduction to prevent adverse outcomes associated with drug use. 

This would include encouraging him not to share drug use equipment if he uses substances again. Encouraging and supporting Harris to increase his use of condoms would reduce his risk of STBBI. A discussion about prevention is an opportunity to encourage Harris to be regularly screened for STBBI to detect asymptomatic infections early. 

Early detection paired with timely treatment can prevent complications and reduce the spread of STBBI. At this visit, informed by the details that Harris has shared, including his immunization history, time since last screening, and sexual and drug use behavior since then, screening for chlamydia, gonorrhea, syphilis, HIV, and hepatitis C would be appropriate. It would also be appropriate to let Harris know that he should access clinical care for testing in the future if he notices symptoms that could be STBBI. 

Testing in the context of symptoms can ensure appropriate management, prevent complications, and reduce spread. As I mentioned, receiving treatment for STBBI is a prevention tool because prompt and appropriate treatment can limit or prevent complications and spread. For Harris, a discussion about STBBI prevention could be an opportunity to share the undetectable equals untransmittable or U=U message. 

U=U communicates the idea of treatment as prevention for HIV. It means that HIV cannot be sexually transmitted from someone living with HIV who is on treatment and has achieved viral suppression. Of the biomedical interventions, Harris should be offered a second dose of vaccine against MPOX to complete the recommended number of doses. 

You should also be counseled about HIV pre and postexposure prophylaxis, highly effective methods of preventing HIV. And finally, consideration could be given to discussing Doxy-PEP to prevent chlamydia, syphilis, and possibly gonorrhea. Returning to our case, Harris indicates that he would like to be screened for gonorrhea, chlamydia, syphilis, HIV, and hepatitis C. 

He provides a urine specimen, blood samples, and collects anal and pharyngeal self-swabs. He opts to receive the second dose of vaccine against MPOX at the visit. He shares that he is hoping to initiate HIV PrEP, pre-exposure prophylaxis, and already has an appointment with an HIV prep clinic and he would like to know more about Doxy-PEP. 

To support clinicians in talking about Doxy-PEP with their patients, we developed a double-sided infographic. I'll spend the next few minutes reviewing the quick reference and you can find it at the QR code on the slide and my colleagues will paste the URL that takes you to this resource into the chat. As I reviewed, there are two recommendations related to the use of Doxy-PEP in cisgender GBMSM and transgender women. 

The first is for health professionals to consider the off label use of doxy-PEP for cisgender GBMSM and transgender women at increased risk of bacterial STI to prevent syphilis, chlamydia, and possibly gonorrhea. The second is for health professionals to discuss the potential AMR risks with patients considering doxy-PEP use. The quick reference resource provides a description of doxy-PEP. 

It notes that the intervention has been mostly studied for use in cisgender GBMSM and transgender women at higher risk of STI. There's no consensus definition of what increased risk is. In the remarks for recommendation one, the NAC-STBBI provides some examples of behaviors that can increase an individual's risk. 

having a recent bacterial STI, having 10 or more sexual partners in the last six months, or engaging in condomless sex with multiple partners, using stimulants during sex, and engaging in group sex are all examples of activities that can increase the risk of bacterial STI. The infographic contains key messages from the remarks that go along with recommendation two. Evidence is emerging about the impact of doxy-PEP use on antimicrobial resistance. 

The extent and clinical significance of these effects are still uncertain because baseline levels of tetracycline class antibiotic resistance in gonorrhea in Canada are high especially among GBMS. Doxy-PEP may not be very effective for preventing gonorrhea in our context. The existing evidence indicates that doxy-PEP use is likely to exert selective pressure that favors the survival of antibiotic resistant strains of gonorrhea leading to increasing doxycycline resistance in gonorrhea. 

As a result, any initial protection that doxy-PEP provides for gonorrhea may be lost. Importantly, the selective pressure may also favor the survival of strains of gonorrhea with resistance to doxycycline as well as to other antibiotics, including antibiotics for gonorrhea treatment like third generation cephalosporins. This may lead to increasing multi-drug resistance in gonorrhea and make treatment more challenging. 

Doxy-PEP use may also increase doxycycline resistance and multi-drug resistance in other bacteria like staphylococcus aureus and shigella. Finally, the infographic includes details about doxy-PEP administration and recommended follow up. Doxy-PEP is taken as 200 mg of oral doxycycline within 72 hours after condomless oral, vaginal or anal sex. 

Individuals shouldn't take more than one dose or 200 mg in a 24-hour period. To minimize antibiotic use, if a doxy-PEP user has condomless sex multiple times within 72 hours, consider one dose 200 mg at the end of the 72-hour period instead of multiple doses. The NAC-STBBI encourages prescribers to reassess doxy-PEP use every 3 to 6 months as an individual's risk of STI is not static. 

Prescribers should follow PHAC recommendations for STI screening, testing, and management. This would include screening for syphilis, chlamydia, and gonorrhea as often as every 3 months. It also includes collecting specimens for gonorrhea culture testing as indicated, including when testing anyone with symptoms concerning for a gonorrhea infection like urethritis. 

Returning to the case, Harris would like to use Doxy-PEP. The slide depicts a sample prescription which incorporates the administration details I highlighted. Harris is advised to obtain STI screening as often as every 3 months and to seek testing for STI if he notices symptoms. 

In summary, this case highlights an approach to incorporating Doxy-PEP into comprehensive STBBI care. Health professionals can refer to the NAC-STBBI's new recommendations and fax resources to provide evidence-based care to patients. 

And we will open it up now for a question and answer for the last bit of the webinar. 

Jessica: thank you so much Genevieve and Andrea.  

Those were great presentations. these recommendations certainly represent a important step forwards. 

they provide a framework with considerations around benefits and risks and I think there's clearly a lot of interest in this.  

I can see the questions rolling in. So, we'll dive right in. 

my first question is going back to the epidemiology and the surveillance portion. I was wondering if you could kind of elaborate on how gender is accounted for in routine surveillance.  

Genevieve: I'll take that one given it's a surveillance question. 

So for routine surveillance sex at birth or gender is captured by the provinces and territories and that's shared with PHAC you know through the national for the national surveillance. So unfortunately there might be some confusion between the two concepts you know in the data collection. however what I can say is that in terms of enhanced surveillance we do make the effort to better distinguish those concepts and intersex as well and trans identity for example. 

So track captures the following data like from the survey participants directly. So we ask sex assigned at birth, gender identity and sexual orientation as well. I would say that within the division we're do making some efforts you know to improve for example our case report forums that we suggest to provinces and territories or that we use for data collection for which we are responsible within PHAC so I hope this answers the question.  

Jessica: great thank you  

I think we'll jump into some of the doxy-PEP material Andrea I was wondering if you could reiterate and clarify which populations are these recommendations are for do they apply to heterosexual individuals? do they apply to women? And perhaps you could expand as to if they will eventually and some of the data on these populations.  

Andrea: Thanks Jessica. 

and thanks I can see the questions rolling in. So I really appreciate everyone's enthusiasm for the topic and the opportunity to kind of clarify some of the information as well. so at this point you can see from the recommendations themselves there's this banner at the top that says that the recommendations that we have are for doxycycline postexposure prophylaxis and the recommendations are really limited to those populations in which we have the best clinical data. 

So that's cisgender, gay, bisexual and other men who have sex with men and transgender women. and we have data from three clinical studies to inform our understanding of the effectiveness of this intervention in those populations showing that it works very well to prevent syphilis and chlamydia. for chlamydia there's some variability in the effectiveness depending on whether people are symptomatic and depending on the site of infection. 

And for gonorrhea across studies there's really quite a bit of variability in gonorrhea and the effectiveness for preventing gonorrhea. Again as with chlamydia related to whether people are symptomatic depending on what the site of infection is but also by where the study was conducted. So we saw in an American study that there was effectiveness for preventing gonorrhea. 

But in studies in France and then in a study among cisgender women that was conducted in Kenya we didn't see that same overall benefit for the prevention of gonorrhea. And there's a question about whether that's related to the underlying rate of tetracycline class resistance to gonorrhea in those populations. And as we're seeing implementation studies be done, it seems more and more common that we're not seeing the benefit for gonorrhea be born out at a population level and we're seeing increasing resistance to tetracycline and gonorrhea as the intervention is used more broadly. 

So there is one study that was done among cisgender women. It was conducted in Kenya. there's a suggestion from hair sample analyses that people weren't actually taking the doxycycline intervention. 

It didn't find a benefit, but that may be related to people not using the intervention. The NAC-STBBI and PHAC generally are continuing to follow the evolution and emergence of this evidence. but at this time we only have evidence for those specific populations. 

And I can put back up the slide that that shows the key questions that the working group had identified. so folks can see we kind of identified these questions that are for specific populations but then for broader populations. and so far the evidence that we've reviewed supported us in developing these targeted recommendations for these specific groups for whom we have the bulk of clinical evidence of effectiveness. 

Jessica: Great. Thanks Andrea. and on a similar note, could you maybe talk a little bit about the counseling side of the prescription? would clinicians provide multiple doses to patients to keep on hand?  

Andrea: so what the sample prescription that I provided is something that people may consider as a bit of a model. so it provides information about how to take the medication. 

generally doxycycline is available as a 100 milligram tablet. So it would be two tablets that you take at one time within 72 hours of having an exposure where we're giving people something to take after an exposure and it's time sensitive. In my opinion, it's better for people to have that on hand and not have to access a pharmacy or health services in order to access the medication. 

so this prescription, this sample prescription would be for 60 tablets or for 30 doses. and so that way people have 30 doses on hand that they would then take following the instructions that are provided on an as needed basis if they've had condomless, oral, vaginal, or anal sex. 

Jessica: Thank you. 

And oh there is there is many questions in the chat. so one of the other questions we had was related to dosing. if there is another intercourse after the initial intake of doxycycline does that provide any protective coverage? 

Andrea: there's a there's an interesting study that's being conducted right now and I think they're still enrolling patients about sort of intermittent dosing of doxycycline and considering some of the pharmacokinetic and pharmacodynamics principles of use of the medication. whether taking it may provide both retroactive as well as proactive protection. For now the recommendations and the evidence that we have are sort of for the 72 hours prior. 

and I think there's sort of a related question to this about what is trying to kind of parse and understand this recommendation around taking a single dose if you've had multiple exposures in that period of time. So if someone say is anticipating having multiple exposures over a weekend on a Friday, a Saturday, a Sunday, instead of taking doses each night, Friday, Saturday, Sunday of 200 milligrams, the recommendation is suggesting out of consideration for antimicrobial stewardship that the individual take the dose at the end of the 72-hour period, providing them this retrospective coverage for the encounters that they had where they may have had an exposure during that window. So, it's the normal dose, 200 mg, but you take it at the end of a 72-hour window if you knew that you were going to be having multiple exposures. 

If you didn't know you were going to be having multiple exposures, you had an exposure Friday and you took your dose on Friday night, but then you had another exposure on Saturday and another exposure Sunday, then at the end of that subsequent window, practically it would make sense to take the dose again because we don't really have the evidence to guide us about this future protection.  

Jessica: great, thank you, Andrea. I I think that's really insightful. 

there are some other questions. I'm attempting to group them in together, but they are coming in very fast. and I think one of the ones I'd like to ask is given the concerns with resistance that has developed for gonorrhea, should we be considering doxy-PEP for prophylaxis here or is it should it be reserved for treatment only? 

Andrea: That's a really interesting question and I think we can see with the different recommendations that are emerging from different jurisdictions and including the most recent recommendations that I've seen which were from the ECDC and they just released those in the last few weeks that public health bodies are kind of coming down on different sides of this discussion. and of course we're also in this moment of considering more seriously principles of antimicrobial stewardship and what antimicrobial stewardship sort of requires of us and how to use antibiotics rationally.  

And so I think some of those considerations inform the recommendations that we did make trying to weigh those risks and benefits, considering equity consequences, thinking that if we know that the populations that we're suggesting this intervention for are disproportionately burdened by gonorrhea, chlamydia, and syphilis. So if we can reduce the burden of chlamydia and syphilis among those populations that are disproportionately impacted, then that may reduce inequities that we're seeing. but on the flip side, if the AMR consequences lead to more antimicrobial resistance in infections that those populations experience, then we may see increasing inequities in outcomes. 

So, some of this is that this is really an evolving understanding of the intervention. we're trying to suggest that people be tailoring the intervention for their patients, kind of considering what their risks are, and then informing them about some of these considerations around antimicrobial resistance and how to rationalize the use. That's part of the reason for including this direction to kind of take a dose at the end of 72 hours instead of 200 milligrams every day if someone's having multiple exposures is trying to kind of strike a balance between prevention with an intervention that's been proven to be effective but avoiding potential harms.  

Jessica: Thanks, Andrea. We have a time for a few more questions. 

I'm just wondering if you could clarify if the recommendations include any information about youth following sexual assault specifically. 

Andrea: that's a very interesting question.  

I know that that's at the top of my mind as well because as Jessica mentioned, I work with a sexual assault center in the community that I live in. 

So, this is something that has been broached, you know, when I'm not wearing my PHAC hat as part of this group of clinicians that that's involved in the care of individuals who have experienced sexual assault. And there have been some questions raised about what is does this intervention have evidence or relevance in that context. in my context, the majority of the individuals that are coming for care are cisgender women. 

and so we don't have a recommend recommendation that extends to that population. We don't have the evidence base to support that. the British recommendations have a little caveat in their guidance suggesting that maybe on a case-by-case basis and if you're considering that there might be a particularly high risk of syphilis then something like doxy-PEP might be considered in that context. 

so the bottom line is we don't have that specific consideration included in the PHAC recommendations at this point in time, but we are aware that this is something that people are thinking and wondering about and continuing to follow the evidence so that we can provide guidance that can inform clinicians in their practice.  

Jessica: Thanks, Andrea. And maybe on a similar note if you could clarify if there's any considerations around mass gatherings that have a high risk of sexual activity such as pride. 

Andrea: Yeah. great question. people must be encountering individuals who have these questions on an ongoing basis that these are all kind of top of mind for everyone. 

I think like in that scenario you may be communicating with individuals who do belong to the populations that the recommendations are developed for. So that would be a consideration in talking with those patients or clients in my work in HIV pre-exposure prophylaxis. I'd see individuals who are going on a cruise or going camping. 

and so if there's a situation that's on the horizon where an individual expects that they may be at higher risk, that might be a particularly good reason to kind of consider whether this intervention is something to layer on to the other STBI prevention strategies that they're going to employ.  

Jessica: Great. Thanks, Andrea. 

Yeah, there is indeed a lot of interest as we go through and you can see all of the different contexts that are people are picturing using this into we will be wrapping up shortly. So I do have time for one last question. and there is some inquiry around the concerns around antimicrobial resistance of the doxy-PEP but doxycycline also being used in kind of cosmetic purposes or treatment of acne. 

and I wasn't sure, this one's kind of out of scope, but I wasn't sure if when you were reviewing the evidence if you came across anything that you'd like to touch on there. 

Andrea: Oh, yeah. I see that there was a question in the chat. 

I mean, I think in all spheres of medicine, we're talking seriously about antimicrobial stewardship and how to reduce overall exposure of populations to antibiotics. certainly that's been when I work in student health clinics and I'm encountering individuals with acne who want to talk about management the first line option would not be oral antibiotics and we've really moved towards as I understand an emphasis on more topical options and options that are not antibiotic based options for that. So I think there is this global move and doxy-PEP fits into this broader discussion about antimicrobial resistance and antimicrobial stewardship more broadly and in addition the populations that we're speaking about here are already disproportioned by antimicrobial resistant infections. 

So, so there's this extra layer of consideration for the burden that's already borne and if these consequences in terms of increasing antimicrobial resistance both in the organisms that we're targeting with the intervention like gonorrhea but also in other infections like shigella or staphylococcus aureus if we're seeing more antimicrobial resistance develop in those infections which already disproportionately impact these same populations then that may exacerbate existing inequities. So I think that's maybe why you see a bit of additional mention and emphasis on antimicrobial resistance both because of this global moment that we're in where stewardship is at the forefront but also out of an acknowledgement of the disproportionate burden of AMR infections that these populations experience.  

Jessica: Great. 

Thank you. that is all the time we have for today. So I want to thank everyone who joined us. 

and a special thanks to my colleagues for their time and insights. Those were lovely presentations. as a reminder, you will receive a copy of this presentation and an email following this session. 

as well as a short feedback form. And we'd really value your input. It helps us decide what we cover in future webinars. 

On behalf of the Public Health Agency of Canada, thank you again for your participation. We look forward to seeing you in future sessions.