Groundbreaking advancements in HIV treatment and prevention

On this episode of the CMAJ Podcast, Dr. Blair Bigham and Dr. Mojola Omole explore groundbreaking advancements in HIV treatment and prevention. They examine various innovative approaches that are transforming the landscape of HIV care.

Dr. Darrell Tan, a clinician scientist at St. Michael's Hospital and associate professor at the University of Toronto, discusses the article he co-authored, "Long-acting injectable antiretroviral therapy for HIV-1 infection in adults." He explains the newly approved long-acting injectable cabotegravir for PrEP, an integrase inhibitor administered as a deep intramuscular injection administered every two months. Dr. Tan highlights its superior effectiveness compared to daily oral PrEP, emphasizing its adherence benefits and potential to revolutionize HIV prevention. Additionally, he covers the long-acting injectable treatment regimen for HIV, which combines cabotegravir with rilpivirine, administered as two intramuscular injections every one to two months. This regimen offers an alternative to daily oral medication, easing the treatment burden for individuals living with HIV.

Dr. Maxime Billick, a graduating infectious diseases fellow at the University of Toronto and co-author of "HIV postexposure prophylaxis-in-pocket," introduces the concept of "PIP" (prophylaxis-in-pocket). She explains how this approach allows individuals who might rarely have high-risk encounters to keep a 28-day supply of PEP (post-exposure prophylaxis) on hand, enabling immediate use after potential HIV exposure. Dr. Billick discusses the importance of ongoing patient-provider relationships and the role of PIP in empowering patients to proactively manage their sexual health.

Throughout the episode, the hosts and guests explore the challenges and opportunities presented by these new treatments. They emphasize the importance of accessibility, awareness, and the need to address health inequities in HIV prevention. The conversation underscores the potential of these advancements to significantly impact public health and improve the quality of life for individuals at risk of or living with HIV.

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The CMAJ Podcast is produced by PodCraft Productions

Transcript

Dr. Mojola Omole:

I'm Mojola Omole.

Dr. Blair Bigham:

I'm Blair Bigham. This is the CMAJ podcast.

Dr. Mojola Omole:

So Blair, today we are talking about some amazing new developments in the HIV treatment and prevention pathway.

Dr. Blair Bigham:

And we are going to go deep, Jola. We are going to look at many different aspects that are sort of revolutionizing the way we prevent and care for people with HIV. We're going to talk about a number of things. We're going to talk about long-acting, pre-exposure prophylaxis, as well as some adaptations to the traditional way we use oral pre-exposure prophylaxis. We're also going to talk about post-exposure prophylaxis and some of the novel ways that that's being prescribed, including as like a pill-in-pocket. Have it before you get exposed, kind of like a pre-post-exposure prescription for prophylaxis. And then we're going to talk about how injectables are revolutionizing the way people are being treated for HIV.

Dr. Mojola Omole:

So what interested you in having this conversation?

Dr. Blair Bigham:

Well, I think that we see a lot of people in probably family practice and emergency medicine and probably all realms of medicine where we worry about HIV risk. And I think as the literature has evolved and our modalities have evolved, it's exciting but also a bit confusing to try to keep up on it all. When people come, they're usually anxious, they've been exposed or they're worried they might be exposed, and they want to know what to do. But also there's a lot of sort of old myths floating around like post-exposure prophylaxis used to be miserable. People would vomit, they would quit. They'd say, "I don't want to take this anymore." It would hurt your liver, but the new drugs don't do that. So I think we have an opportunity here to look at the new science around what we're able to offer and how it can help patients either prevent HIV infections or be more conveniently and safely treated for HIV infections.

Dr. Mojola Omole:

So we're going to be looking at two practice papers in the CMAJ exploring the development of on-demand post-exposure prophylaxis called PIP, prophylaxis in pocket, and long-lasting injectable treatment that can also be used for pre-exposure prophylaxis, PrEP.

Dr. Blair Bigham:

We're going to welcome our panel of authors when we come back. This is an exciting time in the prevention and management of HIV, and two recent articles in CMAJ explore some big developments to bring us up to speed. We've got Dr. Darrell Tan, a clinician scientist in the division of infectious diseases at St. Michael's Hospital, an associate professor in the Department of Medicine at the University of Toronto. He is co-author of the practice article titled ‘Five things to know about long-acting injectable antiretroviral therapy for HIV-1 infection in adults,’ and Dr. Maxime Billick, a graduating infectious diseases fellow at the University of Toronto who's about to start her master's in public health at Harvard, co-authored “Five things to know about HIV post-exposure prophylaxis-in-pocket”. Darrell, Maxime, thank you so much for joining us today.

Dr. Darrell Tan:

Thanks so much.

Dr. Blair Bigham:

We've got a lot to cover, and let's start with PrEP advances. Darrell, a question for you. This long-acting form of PrEP has recently, I think just last month, been approved in Canada. Tell us about it.

Dr. Darrell Tan:

Sure. So it's a really exciting development that we've been looking forward to and anticipating for some time. The product is something called long-acting injectable cabotegravir. So it's an integrase inhibitor, which is a class of medication that we use for HIV treatment already quite widely. And what's unique about it is that it is administered not as a pill but rather as a deep intramuscular injection and using  nanoparticle technology, it is slowly released from that depot site over a course of eight weeks. So people don't need to get this very frequently at all. They can simply come in to receive their injections every eight weeks instead of having to rely on taking a pill. And what's amazing about it is that it's been demonstrated in a couple of really well conducted clinical trials to be safe and effective. The degree to which it's effective is really impressive. Oral PrEP was the comparator, so daily oral tenofovir fumarate with emtricitabine, also known as Truvada, that was the comparator in these trials, and that comparator is already known to be extremely effective if people can take it as prescribed, and yet in these trials, the injectable cabotegravir was shown to be not only non-inferior but actually superior in terms of preventing HIV.

Dr. Blair Bigham:

It's not just a matter of convenience, it actually works better.

Dr. Darrell Tan:

That's right, and the reason that it works better is interesting. Once again, we know that the comparator works beautifully well if it's taken. The key is that it can be challenging for any human to take medications by mouth on a regular basis, which is what we demand of PrEP users in order for that intervention to work. Here, the demands on the individual are perhaps much, much less. They need to be able to adhere to a regimen where they get the injections administered every eight weeks, in other words, every two months. There's a little bit of wiggle room around that, but that really only means six interactions per year where they need to take some sort of action, and the rest of the time they're relieved of that burden of daily pill taking or the regular pill taking, whatever it may be. So it's that adherence benefit that we think has really driven these really impressive results.

Dr. Blair Bigham:

Is it something that people can inject at home, kind of like the way my mom gives herself B12 shots, or do they still have to come back to a clinic every two months?

Dr. Darrell Tan:

It's a great question, and unfortunately the reality is that this is a product that would need to be administered by a healthcare provider. It's a deep intramuscular injection, it's a pretty large volume, and the way it's administered is typically into the butt, so folks would need to show up and have someone else administer it. Certainly it's well recognized within the field that we do need long-acting options that could be self-administered, and so the field has been absolutely heading in that direction, but with this first-generation long-acting injectable product for PrEP, we're not quite there yet.

Dr. Blair Bigham:

For people who are happy to take one pill a day, are there any particular advantages or disadvantages from moving over to the injectable? Any side effects?

Dr. Darrell Tan:

I think the main side effect that the clinical trials have highlighted is the one that you would expect. Folks do have what we call injection site reactions. So it hurts, and there can be reactions on the skin that can manifest as a little bit of swelling, sometimes even a little bit of a nodule that may take a few days to resolve each time. What's encouraging about that though is that does tend to get better over time, so people by the time they're on their third, fourth, fifth injection, for example, note that the severity of those symptoms has gone down, and they typically would rate it as mild by that point. It's been very uncommon for people to, for example, choose to discontinue this regimen solely because of that side effect.

Dr. Blair Bigham:

So what is the patient population that physicians should be prescribing PrEP to?

Dr. Darrell Tan:

Yeah, it's a really important question, and I think the key aspects of the answer that I would highlight is that it's not just one population, first of all, and the second point is that it's not just physicians or clinicians who should be making that decision. It's really people themselves who should be partners in that decision and in many cases initiating that decision on their own. What I mean by those two things is first of all, in terms of there being a number of different populations, the clinical trials have been conducted in two really important populations globally that are at heightened risk of acquiring HIV. The first one being the combination of gay, bisexual, and other men who have sex with men, as well as transgender women who have sex with men. The second population, the second trial was conducted in cisgender heterosexual women in Sub-Saharan Africa. It's generalizable, we think, to any cisgender woman who might be at risk of heterosexual transmission. We do not yet unfortunately have data demonstrating whether or not this strategy of PrEP works in people who inject drugs. So that is a data gap.

The other point that I would make is it is really important that we as clinicians not see our role as gatekeepers. I think healthcare providers have a really, really critical role in terms of actively recommending products that we recognize might be of benefit to individuals that we have the privilege of serving, but it's not our role to block a request for PrEP from someone who might come to us and say, "Hey, I think this might be for me." And the reason I say that is because we all know that there's a lot of stigma associated with many of the activities that can put someone at risk for HIV, be it sexual activity, injection drug use. There can also just be a lot of discomfort and shame and privacy concerns around what someone might be willing to tell a healthcare provider, yet they know that there is some risk that they experience. And so if someone does come forward and ask for PrEP, I think it's really important for us as clinicians to be open to that request, to give them information, and in the vast majority of cases, honor that request and work with the person to help them access this prevention technology.

Dr. Blair Bigham:

I feel like in the gay community, everybody knows about PrEP, like the marketing has been successful. But what about that second population you spoke about? Are there blind spots that you are seeing either in family physicians or in populations who could benefit from PrEP but there's a disconnect, family docs aren't thinking about it or patients aren't thinking about it?

Dr. Darrell Tan:

Absolutely. I think there are a lot of blind spots, as you say, in terms of who clinicians think might be a good candidate for PrEP or any other HIV prevention technology and who isn't. The first thing to say is that, Blair, although you rightly point out that among gay, bisexual, and other men who have sex with men, awareness of PrEP is fairly high in an industrialized setting like Canada, I think it's important to start and point out that it is absolutely still not even, and there, in particular, are really profound racial inequities that persist, and so it actually is important for us to actively point that out because otherwise we really do risk perpetuating this assumption that everyone has equal access to the information and therefore everyone has equal access to the intervention. That's not true, and we see that played out particularly along racial lines in this country and other high-income countries that we would compare Canada to.

But in addition, it's absolutely also true that other populations, notably cisgender heterosexual women, which was the second trial demonstrating that long-acting cabotegravir works in. There is really a very dramatic gulf between the amount of PrEP uptake in usage and awareness in that population in Canada compared to, yes, gay, bisexual, and other men who have sex with men. And that's a huge gap that we need to attack in multiple different ways. I think absolutely one important way to try to overcome that is to raise awareness among clinicians that, hey, someone who does have multiple partners, who's a cisgender woman, should be made aware of PrEP, should be counseled about it, should be encouraged to think about it, and of course, prescribed it if that's what they choose. But I think it's also important to recognize that risk for HIV manifests in such different ways in different people, and sometimes it can be challenging for not only the clinician to identify but also the person herself to identify. A really classic scenario that we know is well described in the HIV literature is a person, in this case, for example, a heterosexual cisgender woman, who believes that she's in a monogamous or closed relationship, but in fact, the reality is that she's not.

And if in that sort of dynamic, there's gender dynamics at play, there are power dynamics at play, it can be, of course, very challenging for there to be an opening for a conversation about PrEP at all if there's not full awareness of the reality of the risk situation. I think that really poses a big challenge for us, not only clinically but also societally at trying to overcome.

Dr. Mojola Omole:

Maxime, I just wanted to get your thoughts. Is there a way of expanding who we naturally think we should have conversations about PrEP to? Say I have multiple sex partners. Is that something that my primary care person should be like, hey, how do we broach that conversation with our patients when they might not think of themselves as necessarily being high risk for HIV exposure?

Dr. Maxime Billick:

I think a lot of that is about relationship building. Unfortunately, not everyone has a family physician or necessarily one they trust here in Ontario, and we know that a substantial amount of young people in Ontario and across Canada don't have a primary care provider who they go to frequently. But I think at least in my personal practice, a lot of what I do is normalizing language and normalizing talking about sex, which I think some communities and groups are really good at and other communities and groups are not. Something I actually learned from Darrell was when you're asking someone a sexual history, if it's important, you taking on the role of asking about particular sexual acts yourself and not necessarily asking the patient to say it. Of course, sometimes that might be tough if it's a first visit, but I think in terms of recognizing potential risk among patients, a lot of it will come with relationship building and trust, and a lot of it will also be coming from the patients themselves, if that makes sense.

A lot of these medications are relatively low risk from a patient perspective, and I think that if there's a degree to which they may be helpful in someone's life in preventing HIV acquisition, not to say that we should be giving it out like candy, but I do think that there are a lot of missed opportunities for prescription or even for talking about it, right? We can introduce it to people, and I often do in my fellows clinic over the past two years to patients who've never even thought of being on PrEP before. They don't have to make a decision in the moment; they have to know it exists. I think another important thing, and this has been talked about ad nausea, like I'm not reinventing the wheel by saying this, but you look at who is represented in a lot of the ads for PrEP when you walk at Bay and College, and it's great that there are ads at all. It's great that people are talking about it, but a lot of the representation is gay and bisexual men who have sex with men, right? It's two men affectionate in a photo, and I think it's so cool that we can have that in the middle of downtown Toronto when maybe 15 or 20 years ago, it wouldn't be there, but there are no women represented, there are no women of color represented, there's no visibly indigenous people represented. And so the same way that we've made steps within our healthcare facilities to have people reflected in some of the imaging and language, I think we have to do the same for PrEP so people know that it applies to them as well.

Dr. Mojola Omole:

And then my next question is, I'll use the example of the patient that I had met in the emerg, and we talked about PrEP because I was like, okay, well, I think this is a conversation we should have. What should have been my next step? Because my next step was, I was like, okay, well, there is a sexual health clinic attached to where we are. You should call them on Monday to make an appointment. And when I was talking to Blair, he was like, well, that's probably a missed opportunity. What should I have done differently if I thought, okay, this person seems open, like we had enough of a rapport that we're open to the conversation. What should I have done differently in terms of next steps for them to explore starting PrEP?

Dr. Maxime Billick:

I think it depends where you're located. So I'm going to speak sort of Toronto centric, recognizing that some of the resources in rural settings are different. Some of the resources in other provinces and other countries are different. Here in Toronto, we have a lot of walk-in clinics where people don't have to make an appointment. There's a lot of sexual health clinics as well. There is specific testing that needs to be done before PrEP is prescribed, and so unfortunately it's not exactly the type of thing that you can prescribe in an emergency department. We have to make sure that people are, in fact, HIV negative. There's certain STI testing and biochemical testing that should be done in advance, but certainly having the conversations and providing people with the resources to be able to establish care at a potential clinic is helpful. I'm not sure if that fully answers your question, and I might open the floor to Darrell as well if he has anything to add.

Dr. Darrell Tan:

I would add to the conversation that none of this falls to one particular provider or one particular discipline. I mean, I think it's really important that we think about a healthcare system that has multiple entry points for PrEP, just like any other health intervention. And it's amazing to hear, Jola, you talking about conceiving of providing PrEP or linking someone to PrEP in an emergency department setting, which is not, I think, a setting that the average healthcare provider thinks of as an opportunity for PrEP. It absolutely could be, and there's actually a rich literature looking at exactly that, starting to initiate people on PrEP through emergency departments analogous to doing so through our sexual health clinics, our primary care clinics, our infectious diseases clinics. There's multiple entry points that we should all be thinking about, and it doesn't fall to one particular discipline. Absolutely there is,I completely agree with what Maxine was saying, which is when starting someone on PrEP, we absolutely would like to document that they are indeed HIV negative at the time that they initiate PrEP, and that is clearly laid out in clinical guidelines around the world. That being said, I think it's also true that we have also recognized that there is increasing urgency in our response to the HIV epidemic, and that urgency demands new innovative approaches. And as a result of that, people have also been bold and innovative in not letting that perfect be the enemy of the good, to borrow that classic saying, and that there may be circumstances in which an institution, a provider, a discipline wants to set up a clear care pathway in which they may use an imperfect rapid test and then choose to initiate someone on PrEP thereafter, or they may even be so bold as to, say, provide an initial small supply of PrEP, but with rapid reliable linkage to a specialty service that can take on fuller ownership of this.

The amount of harm done in terms of potentially causing resistance while it exists is fairly minimal if we provide only a limited supply that allows someone to immediately engage with this in the moment that it's real and meaningful to them, such as during a healthcare encounter with an emergency physician. So I just wanted to say that I think that we do need increasing creativity and innovation and boldness when it comes to tackling this epidemic that has really not declined to the extent that we are capable of in a country like Canada.

Dr. Mojola Omole:

So how expensive is it?

Dr. Darrell Tan:

Yeah, so the good news is that the drug that we typically use as PrEP, which is tenofovir fumarate with emtricitabine, or the trade name Truvada, has dropped down in price dramatically to the cost of something like 200 and change dollars for a 30-pill supply. Now that is still a lot of money.

Dr. MojolaOmole:

That is so much money.

Dr. Blair Bigham:

It was so much more though. It used to be over a thousand bucks.

Dr. Darrell Tan:

It's four times less than it used to be. However, the good news on that front is that first of all, we are finally at the point where jurisdictions across this country have different degrees of public reimbursements for PrEP, and just recently the province of Manitoba took the really bold and commendable step of making access to all antiretrovirals, be it for treatment, PEP, or PrEP, universally covered, which is a bold step that we need from coast to coast to coast. Absolutely. And there are other jurisdictions in this country that have implemented that years ago. So those are really to be commended and to be emulated across the board. The other encouraging thing though is that in settings where perhaps there still is a copayment required, access isn't quite universal. There are other regimens that can be used that effectively do allow someone to save on costs. In particular, I'm thinking in referring to the use of what we call on-demand PrEP, sometimes also called 2-1-1 PrEP, which has been studied and demonstrated to be effective and safe in gay, bisexual, and other men who have sex with men. This allows someone to just use a few doses of PrEP around the time of a particular anticipated exposure. In other words, having sex and not needing to take the pills at other times. And you can imagine that depending on the frequency with which someone's having sex, this could accrue considerable cost savings if they're simply not using the medication as often.

Dr. Blair Bigham:

That one's interesting to me. Just lay that out for me. How exactly does that work?

Dr. Darrell Tan:

So the way it works is that gay, bisexual, and other men who have sex with men could take two pills two to 24 hours before sex, followed by one pill the day after and one pill the day after. So we call it 2-1-1. I like to tell people that it rhymes with 4-1-1 or 9-1-1 if those are easier to remember, 2-1-1. And we have great data generated in part in this country, in Canada, demonstrating that this is highly safe and effective at preventing HIV if people can use it properly. It's important that people recognize that that first dose is two pills. It needs to be taken not immediately before sex, at least two hours before, not more than 24 hours before. So the way that we like to explain it to folks is that if you anticipate having sex tonight, then during the day is the perfect time to take those first two pills. If sex happens, then you end up taking the next pill the next day and then the final pill the day after that. If sex doesn't happen, no harm done. You've taken that initial dose and you simply don't need to continue.

Dr. Blair Bigham:

Let's take a break from talking about pre-exposure prophylaxis and just talk about how this new injectable has changed the game for HIV treatment. Same idea, long-acting cabotegravir injection. How can that be a game changer for people who are living with HIV infection?

Dr. Darrell Tan:

So the regimen itself is actually the combination of two medications. One is the same drug, long-acting injectable cabotegravir, but it's paired with another antiretroviral drug, which is called rilpivirine, and the two medications are administered as two deep intramuscular injections every one month or every two months. Both regimens have been studied and demonstrated to have high efficacy. I think there's a lot of ways in which this has really revolutionized the field for people, but I think that the real drivers are the benefits that it offers to people in terms of the adherence burden or the psychological burden. People really describe a feeling of a burden lifted off them when they switch to this regimen, and many people who are using it have really noted a lot of benefits.

Dr. Blair Bigham:

For family doctors who are doing sort of maintenance care of people who have HIV, if their patient comes to them and says, "Hey, I just want to switch over," are there any special considerations, any side effects, any patient populations who wouldn't be a candidate to switch over to the long-acting injectable?

Dr. Darrell Tan:

There are a number of clinical considerations that need to, of course, be taken into account when making a decision to start this drug, like any other medication. Certainly we need to make sure that the person has a virus that is anticipated to be susceptible to these two drugs, as we do with any other HIV treatment regimen. It's also important that the person not, for example, have hepatitis B co-infection, which is an issue we do sometimes see in the HIV clinic. The reason for that is that this is a regimen that doesn't have activity against hepatitis B, and we can readily treat both of those viruses in someone who has both conditions with a wide number of oral regimens. In terms of side effects, absolutely there are the anticipated side effects that people would expect with a long-acting injectable formulation. So it's going to cause pain, it's going to cause some of those same injection site reactions, but again, they tend to become mild over time, and many folks find that they can tolerate them better. There is one last thing that's I think important to recognize, which is that the field is still grappling with trying to understand why in very rare cases we do observe that folks, despite getting these injections on time, actually do seem to lose control of the virus, that it does seem to be associated with virologic failure. In other words, in not being undetectable anymore for reasons that we still don't entirely understand. Some of it is explainable by resistance, some of it might be related to certain subtypes of HIV, some of it might be related to factors like body mass index being high, but we don't actually still have a full grasp of this. It is a rare outcome, but it is something that we do counsel folks about consistently before they embark on this new form.

Dr. Blair Bigham:

So these long-acting injectables have really shaken things up for both HIV treatment and prophylaxis, but there's also something new on the front of post-exposure prophylaxis. Maxime, do you want to tell us about that?

Dr. Maxime Billick:

Sure. Thanks so much. So the new thing that you're referring to is PIP, or PEP in pocket, lots of acronyms there, but it's essentially a mechanism by which we identify those who have a low number of potentially high-risk encounters, often sexual encounters, sometimes IV drug use encounters per year. We usually say about zero or one to four, and we provide them with a 28-day prescription of post-exposure prophylaxis, or PEP, in advance, and this is usually guideline derived. So oftentimes here in Canada, it's bictegravir, FTC, and tenofovir alafenamide, but could also be other drugs depending on where people are and what countries they're in. We instruct them to fill the prescription in advance. They have the bottle of pills at home, ready to go in their medicine cabinet, and we counsel them on what to do if a potential risk encounter occurs. So effectively, let's say they have unprotected sex or they have sex and the condom breaks, then they have this post-exposure prophylaxis at home that they can start essentially immediately after the risk encounter. And I think this is important because the way that our healthcare system is set up right now in Canada and in many other countries, if people were to take post-exposure prophylaxis, they'd have to go and sit in an emergency department at four in the morning after, for example, potentially being assaulted, or they would have to get up the confidence or wherewithal to present to care. Oftentimes, people are either survivors of sexual assault or might have a degree of shame about the encounter or might just not want to talk to a stranger about the recent sex that they just had. And so this sort of subverts that need for presentation to an outside healthcare provider while also building a degree of rapport and association with a healthcare provider or a clinic that they can then go reach out to. I think it's important to say that we also have ongoing relationships with these patients. So we have routine visits every six months to do STI testing, HIV testing and counseling, and to figure out if PIP is still working for them. If someone is having lots of risk encounters and they've taken PIP five times in half a year, that's not appropriate and they should probably be on PrEP or pre-exposure prophylaxis might be a better modality. We see in some of our research that about a third of patients actually switch from PrEP to PIP and a separate third switch from PIP to PrEP. So there's a bit of fluidity oftentimes driven by people's relationship status, where people are in their life trajectory, how often they're going out or hooking up with others, et cetera.

Dr. Mojola Omole:

What's the patient experience been regarding with PIP compared to PEP?

Dr. Maxime Billick:

We have a lot of patients who are very excited about it. I don't have them in front of me, but I actually have a couple of quotes in a few of the presentations that I've given recently that really highlight, I think, a degree of patient independence and control over their sexual health. And I think that's really important and sometimes minimized in patient care and in the importance of people feeling like they have control over their sexual health. I think people also appreciate having an ongoing provider that they can go to and ask questions to and have a touchpoint with healthcare even if they don't have a family physician perhaps to be able to talk about some of these HIV prevention modalities.

Dr. Mojola Omole:

What is the target patient group for PIP?

Dr. Maxime Billick:

I think that there are many patient groups in which we think it will work. The greatest uptake has overwhelmingly been gay and bisexual men who have sex with men. I do think that there's a really great opportunity, as Darrell highlighted earlier, to make some forays within other populations. So specifically cisgender women, in whom we haven't seen the uptake of PrEP be nearly as great as we have in the gay, bisexual MSM population, but also I think not as great as we thought we would see. Right? So I think that's important. The other two populations that I think are really important are rural populations. So we've seen all over the news last summer. It's starting again this summer. Rural emergency departments closing, staffing is really thin. People still have sex outside of big cities and certainly HIV is concentrated in cities..

Dr. Mojola Omole:

Sometimes more. I grew up in a small town. 

Dr. Maxime Billick:

So you can attest to it, and certainly HIV is concentrated in big cities, but in places where there is decreased access to healthcare or to emergency departments, this subverts some of that need to present acutely to care. I also see it having a potential effect in travelers, people who might not always need to take PrEP and who might not always anticipate risk exposure. If you know you're going out to bring someone home, of course taking 2-1-1 PrEP, great, and you can take the two pills in advance, but if it's an unanticipated risk encounter, there still should be the opportunity for HIV prevention because we know that post-exposure prophylaxis works. It's guideline-directed in many guidelines around the world. And so I think that it's more so just an implementation mechanism to allow people to make sure they have access within that 72-hour time period because post-exposure prophylaxis needs to be taken within 72 hours.

Dr. Blair Bigham:

So PIP isn't so much for people who might have occupational exposures very rarely. It's more for people who would have social exposures in their day-to-day lives.

Dr. Maxime Billick:

I might just tweak that because sex work is work, and so in that case, I would consider it an occupational exposure, but perhaps not the traditional occupational exposure of a large bore needle stick or placing yourself in the OR. 

Dr. Blair Bigham:

In the ER, most of the people who come to the ER asking about PEP are people with occupational exposures, and I actually deem their risk to be so remarkably low that I usually advise against PEP. I won't say no if they feel strongly about it, but that's not really the population that you're sending home with a 30-day supply.  These are people who, if they had an exposure, their exposure would be much riskier than, say, that needle or somebody spat in their eyes or something like that.

Dr. Maxime Billick

Totally, and oftentimes the situation that I think you're describing is a patient who is reliable enough to come to their surgery. We have the opportunity to do HIV testing on the source patient or viral load often—not always for sure—but often have some sort of engagement in care, and so we know the source patient and their potential risk of transmission. Whereas if someone is picked up at a club and then our patient never sees that partner again, we don't know what that risk exposure is.

Dr. Mojola Omole:

Do you think that, because I'm just thinking of, I'll put myself out there, in my younger days, we'll go to Vegas, have some fun, should it be that PIP should be available over the counter? Should I, maybe back in those days, if let's say it was available, if I thought it was a risky encounter, I should be able to go to the pharmacy and pick up some PIP?

Dr. Maxime Billick:

I would love that. I think that we put…

Dr. Mojola Omole:

I would love a hookup also. Thank you. 

Dr. Maxime Billick:

There are some, again, resistance and there are certainly things that are potentially problematic about it, so I'm not going to say yes without any asterisk or caveat, but I will say that we are putting more and more reliance on pharmacists and on patients themselves to make the assessment if a certain medication should be taken. So for example, if someone has unprotected sex, if a cisgender woman with uterus has unprotected sex with a man, they are able in Canada to go and pick up Plan B, right? We don't necessarily need them to go to an emergency department. You can buy fluconazole over the counter for a vaginal yeast infection. We also trust patients. An example I often give is like people who are about to give a presentation and they take a beta blocker if they tend to have panic attacks before they go on stage. We trust patients and we're increasingly trusting pharmacists to make the assessment whether something should be prescribed, and so maybe over the counter is a little bit preemptive, but certainly going to a pharmacist and explaining a situation I think would decrease a lot of the barriers that we do see with regards to post-exposure prophylaxis use.

Dr. Darrell Tan:

If I could riff off what Maxime has just so nicely described, that in fact, there are jurisdictions in this country in which pharmacists are now empowered to prescribe, and there are movements afoot to expand this. In Nova Scotia, for example, pharmacists are involved in providing post-exposure prophylaxis. Pharmacists can prescribe in Saskatchewan for certain things in Alberta, so we're definitely moving in that direction.

Dr. Mojola Omole:

With all of these new exciting medications and pathways for HIV prevention and treatment. How has been, and I'm going to preface it  because I do think there are different gay communities, there is the Church Street, white gays, and then there is everyone else. What has the response been in terms of uptake and interest in these new treatment modalities?

Dr. Darrell Tan:

Yeah, I think that we see very clearly in the data, it's been very well documented in the United States and no reason to think it's any different in Canada, that there are huge health inequities in terms of awareness, uptake, persistence, adherence, all the different steps along the PrEP cascade, as we call it, with racialized communities, other equity-seeking groups within the population of gay, bi, other men who have sex with men, and this is a huge concern. I think it has a lot to do with, as we were speaking about earlier, how this has been marketed, who people perceive this to be for, who sees themselves reflected in the publicity, but also even in the research, and I think that's a call to us as researchers as well, to be as inclusive as possible to help ensure that the data that we provide is truly representative of the populations to whom we think that could benefit. I think there is a huge gap in this country and many other settings in terms of getting the word out about these HIV prevention modalities, and this is something I feel very passionate about. I like to give the example that I don't think anyone in this country would have any doubt whatsoever about whether they thought that federal, provincial, territorial, local public health authorities thought that it was a good idea for them to go out and get a COVID vaccine. I think that message is absolutely crystal clear. It's likewise crystal clear that we think that everyone should get a flu shot in this country every single autumn. They may choose to do something different with that information, but that message is out and understood. It is not clear, I don't think, to people that public health authorities, clinicians think that HIV PrEP, HIV PEP in pocket is a good strategy. There's a lot of silence around this, and I think this perpetuates these inequities that are so critical. We need to be trumpeting the fact that we have safe, effective, in some parts of this country, universally available technologies that can prevent HIV, one of the greatest epidemics globally of our times, and that there's a lot of silence. A lot of the vocal publicity and messaging around this has come from individual private entities, and we can perhaps therefore understand why they may feel that they're going to cater to their specific clientele, and that's a decision that they make and may suit their purposes, but from a public health perspective, we need to be widely advertising, creating demand, as it's often called, for these products. Because unless we do that, and unless people see themselves reflected in the information that they're exposed to, we're perpetuating the lack of access to these interventions, and that's to say nothing of the very concrete need to make sure that it truly is universally accessible from a financial perspective, which is still not the case across the country.

Dr. Mojola Omole:

Maxime, do you have anything to add to that?

Dr. Maxime Billick:

I agree wholeheartedly with what Darrell has said, and I also just, I think about proximity of access. I think about how hard it is for me as even someone with a job and a salary to get my ass to go to the doctor or seek care when I have everything lined up from a privilege perspective to be able to. I think that if you have to schlep downtown or to a city or outside of your community to access some of these resources, people are really going to be dissuaded from seeking them, and so I think it's really important, recognizing that as a fellow I've done a lot of my work in downtown tertiary quaternary care centers, but I think it's really important that many of these medications and services be available within the communities where the need is greatest and that we don't force patients or people to seek it from really far from where they are.

Dr. Mojola Omole:

For sure. That's great. Thank you. Thank you guys so much for joining us.

Dr. Blair Bigham:

Thank you. That was amazing.

Dr. Maxime Billick:

Thanks so much for having us.

Dr. Darrell Tan:

Thank you.

Dr. Blair Bigham:

Dr. Darrell Tan is an associate professor in the Department of Medicine at the University of Toronto, and Dr. Maxime Billick is an infectious disease fellow also at U of T. 

Jola, that was a whirlwind.

Dr. Mojola Omole:

It was great. My first thoughts were that we live in such a Puritan society in Canada where we view the conversations around sex and HIV from a very, personally, an overly religious view of it and not from a clinical medical view. The concept of PrEP, PIP should be viewed the same way. For me, when I'm packing for a trip, I pack Cipro, I pack Flagyl, I pack my Dexilant, and I should be able to say, okay, I'm going to pack some PIP too, because not quite sure where this trip is going to take me. I do think we need to get there as a medical community and then as a society at large where we don't have shame around conversations about PrEP and now PIP.

Dr. Blair Bigham:

There's still a lot of stigma around it for sure, but I also wonder if there's just less concern if it's just less worrisome to people. I mean, I think about when I came of age 20 years ago and I was in that weird decade after the HIV crisis. People were not dying of HIV the way they were in the generation before me, but we didn't have PrEP and we were terrified of HIV, and if you had an incident, then you were running around. I remember one year I was running around New York City one summer trying to find a way to get PEP, and the New York City Public Health Department just gave me a 30-day supply, and I was like, oh, wow, thanks for the thousand dollars of pills and that moment, that was super stressful. Then PrEP came out, and the next thing you know, condoms were deemphasized. People weren't really worrying so much about their sexual encounters, and we've sort of seen that rebound in sexually transmitted infections as people are less worried about being protected in their sexual activities.

Dr. Mojola Omole:

I think it's important to emphasize that this goes beyond gay, bisexual men who have sex with men. In the US, the highest rate of HIV and new HIV exposures is in black women, and they're cisgendered, heterosexual black women. So we need to keep that in mind that this is not quote, unquote a gay thing, because I think oftentimes even clinicians like to, well, we don't have to think about that. I don't have that population. Everyone is your population because everyone has exposure risk, whether that is through sharing needles or that is through sexual exposure.

Dr. Blair Bigham:

I totally agree. It's like society has collectively forgotten about just how terrible the nineties were for many different populations.

Dr. Mojola Omole:

I think they didn't even think it was that terrible then either.

Dr. Blair Bigham:

Jola, how can we summarize this for people who are booking appointments in their clinic tomorrow? What's your top takeaway?

Dr. Mojola Omole:

My top takeaway is that as a frontline physician, you need to have the conversation with any of your patients if they're sexually active. Also, if they are sex workers or if they have exposure through sharing needles, you need to have the conversation with them. If it's something that you don't feel comfortable with, make sure you're able to connect them at that very moment with a clinic that would be able to help them. And we need to just view it the same way we view the HPV vaccination. Right? I have family physician friends who give it to their 70-year-olds who are sexually active because you can still get HPV at 70. We have to view HIV at risk exactly the same way.

Dr. Blair Bigham:

Absolutely, and expanding that toolkit that we have now with new pharmaceuticals, the injectables, new ways of delivering old drugs, like the 2-1-1 model for PrEP. Everything in the toolbox is just one more opportunity for you to make the right thing to do, the easy thing to do for that patient at risk.

Dr. Mojola Omole:

A hundred percent.

Dr. Blair Bigham:

That's it for this episode of the CMAJ podcast. If you like what you heard, please give us a five-star rating wherever you download, and make sure you share us with your networks and leave a comment. The CMAJ podcast is produced for CMAJ by PodCraft Productions. I'm Blair Bigham.

Dr. Mojola Omole:

And I'm Mojola Omole. Until next time, be well.