Expert Guidance Podcast on Clinical Challenges in HIV Prevention and PrEP: Insights From the National Clinician Consultation Center

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Expert Guidance Podcast on Clinical Challenges in HIV Prevention and PrEP: Insights From the National Clinician Consultation Center

Dr. Carolyn Chu (National Clinician Consultation Center): Hi. So, thank you so much to our organizers today and also to my colleague, Dr. Chris Bositis. We are so pleased to be here. So, what we were going to do with today's format is make it very interactive. Dr. Bositis and I are going to talk through a couple of sort of key myths or misconceptions that folks might be hearing about in their community, and then that will hopefully set us up pretty well to sort of transition to a next section, which we've titled sort of challenges, conundrums, you know, things that are just coming up as – as people are prescribing PrEP and using more of it.

Myth 1: PrEP Is Only for “Certain People”

Dr. Chu: All right. So, let's just kick this off with our first myth, which is really sort of I think, where we want to lay some really important groundwork. Our PrEP line has been up and running since late 2014, 2015. And actually, we continue to get calls to this day around sort of eligibility for PrEP. You know, who is the right candidate? Who could I be having these types of conversations with? And I think it's really important to start off today's webinar by trying to dispel this myth. You know, that PrEP is only for "certain people" or certain populations. Chris, what do you – what do you think about that? Have we seen an evolution in the calls and sort of types of cases that we're noticing on our PrEP line?

Dr. Bositis: Yeah. Great question, Carolyn, and thank you for asking it. You know, I think that it's really important to note that we in spite of the fact that PrEP has been around for more than a decade, we still see really significant disparities in PrEP use among different populations. And part of what's driving those disparities is a lack of awareness or familiarity, both – among both providers and among populations or/and individuals that would benefit from PrEP use. And additionally, we know that stigma and fear can also – is also driving this – this myth to – to some extent.

And so, for example, when PrEP was first rolled out in a large scale, a lot of the advertising that was put out there really focused on certain – certain communities at the exclusion of others, leading many people to believe that PrEP just really wasn't for them. And as – as a provider who is working in a predominantly Latino community where much of the epidemic was driven by injection drug use, this was a real issue because many of the people that – that we were serving felt like the ad – those ads just they weren't speaking to them. And – and it meant that, you know, PrEP must not be for them.

Similarly, I think it's important to note that – that many people may be reluctant to share their interest in PrEP because they are afraid that they will be labelled as – as promiscuous or otherwise judged by their provider. And I think that's an important thing to note, because we really want to work on creating safe spaces where people can feel comfortable sharing their interest in – in this important intervention.

On the provider side, we know that many – many providers still feel like they – they don't know enough about PrEP to prescribe it or that it really should remain something that just HIV or ID specialists prescribe. And so, in that vein, I think we were really encouraged to see the recently released ACOG guidelines on HIV screening and prevention regarding PrEP counselling and prescription, where they state explicitly that all health care professionals should proactively initiate discussions about PrEP.

And so, related to that, Carolyn, I was wondering if you would be willing to speak a little bit about how we can expand universal messaging around PrEP in our practices.

Universal and Inclusive PrEP: All Roads Lead to Discussion

Dr. Chu: Thanks for that, Chris. I mean, it's also important, I think, to note and appreciate that we've actually seen some shifting in the guidelines, right? And so, we know that there are many folks here who I think are practicing in the US and then also outside the US. And these are just a couple of the examples that we – we did sort of note this updated language, you know, sort of getting at the issue of PrEP eligibility. The CDC guidelines now actually say prescribe PrEP to anyone who asks for it. And they had actually developed this algorithm that the sort of that folks can see here on the left side of the slide.

And if you just go to that bottom row that's in sort of various shades of green, there is not a single sort of sexual exposure pathway where – where you see that the at least the CDC says, oh, no, don't talk about PrEP, right? If there are people that are, you know, sharing information that it does seem like there would be benefit, that there might be some exposures of concern, yeah, go ahead and prescribe right at that initial visit. But even for scenarios where maybe the person isn't walking out the door with a PrEP prescription, at least you're bringing up that conversation. You're letting people know, you know, this is an option and even if we're not yet ready to go there today, let's have you come back and talk a little bit more and see if things have changed or, you know, I can answer more questions for you.

And so really, there's not a single scenario here, at least in the CDC guidelines where, you know, the – or at least our guidelines in the US are saying, no, don't – don't talk about it, right? And similarly, I think with other really important organizational bodies, IAS, USA, they actually go a step further and say, you know what, let's not get so hung up about specific risk criteria or specific screening tools. Just offer PrEP to anyone who is sexually active. Certainly, those who are coming into your office asking for it or like you were we'll get into a little bit later, maybe people who use drugs or people who inject drugs, we know that that is a population that has been vastly overlooked in the science, but also, I think in the, you know, clinical implementation. And so that we just know there's – there's large unmet need there.

Dr. Bositis: I was going to say one of the things that I meant to mention previously is that in many studies looking at PrEP awareness among people who are using drugs the percentage of those stating that they have heard of PrEP before, even now in the 2020s, remains low, less than 50% in many published studies. So, we still have a long way to go there.

Dr. Chu: Yeah, no, that's perfect. Thanks for that. And I think the one thing that we also wanted to highlight in the British guidelines is, and we'll get into this a little bit more when we're talking about the challenges and controversies, is that they actually say, you know what, regardless of sort of what someone's gender or sexual orientation or just, you know, we know that there's many different kinds of exposures happening. Again, it's really sort of getting to this – this mindset and this framework of being super inclusive, universal, just bringing up as part of standard of care.

Multilevel, Intersectional, and Practical Strategies to Spark PrEP Discussions

And so, related to that, we recognize that while there's a lot that we can do to improve how we are counselling people about PrEP in the exam room as clinicians, there are a lot of structural and multidisciplinary approaches that we can take that can really improve the rollout and uptake of – of PrEP as well. These – these interventions include things like expanded signage in clinic in public spaces.

They include providing handouts in people's native language that addresses their questions about PrEP and that dispel common myths about PrEP. We also know that targeting providers and providing tools for providers like EHR prompts and integration into the healthcare bundles. Those kinds of things can really make a difference in terms of expanding PrEP access and the likelihood that PrEP will be discussed during a patient visit.

And lastly, quality improvement projects that are focused around PrEP, those also can really have a significant impact on – on expanding PrEP use in among those who really need it.

Myth 2: PrEP Is Unsafe

So, that brings us, I think, to our – our next question, our next myth related to PrEP use, which many people when asked about PrEP, will say, well, you know, doc, I'm not sure I want to take PrEP because I've heard that it's not safe. Carolyn, what can you tell us about where that myth comes from and what we actually know about the safety of PrEP?

Dr. Chu: Yeah, no thanks, Chris. And I think we also just wanted to highlight that – that, you know, especially now that we're seeing more options for PrEP being approved, it is really important for clinicians to sort of have an accurate understanding of sort of what the – what the safety track record is so that people feel comfortable asking questions. So, I took a little detour in the history archives. And what I found and sort of reminded myself about was that actually if folks have been sort of in the HIV treatment space for a while, they might remember that we were starting to hear about some of the first lawsuits that were actually filed back in 2018 F/TDF, which had actually been, you know, sort of one of the first options that was studied as PrEP. But for a long time, we had been prescribing it as part of a comprehensive antiretroviral treatment for people living with HIV.

But really right around that time, there were a lot of commercials starting to come out, a lot of like direct to patient advertisements, letters. We were even seeing some stuff targeted at prescribers sort of putting this scare out there, like, oh, you know what? If you've been on F/TDF and you've had a fracture, you've had kidney problems, you know this is the culprit. But what was also happening around the same time is we were actually seeing the first landmark study of F/TAF as a second PrEP option. And so, it was almost like this confluence of things just happening coincidentally that, you know – you know, we'd had F/TDF available as PrEP, but we're getting some messaging that sort of probably confused people. And then at the same time, the DISCOVER investigators were announcing their incredible results of sort of this other oral version of PrEP that, you know, there was, you know, thought that maybe it could be better for some folks.

But I think it's also really important just to sort of, you know, remind all of us about what really the DISCOVER trial found. They actually found that with both F/TDF and also with F/TAF, which was what they were investigating, that adverse events were actually very, very, very uncommon, extraordinarily rare, and ultimately did not end up in the participant discontinuing, you know, their – their treatment. And in the real world, I think what's important is that for – for the vast majority of people who are on oral PrEP, it's probably not necessary to sort of pre-emptively switch folks to F/TAF. Now, we know that there might be external drivers.

But – but most people could actually stay on F/TDF. And if you're practicing in a setting where people are facing high copays or whatever, I mean, there's a generic available for F/TDF that we don't have for F/TAF. And I think you shared a study from a group in Boston that actually looked through their – their sort of PrEP users and found that several people had been switched to F/TAF and probably really didn't need to be switched. They could have very safely stayed on F/TDF. And so, I think we want to just show up today to say that all oral options of PrEP are quite safe now there's monitoring that's involved – involved, and you know the guidelines go through that. And also, the injectables we're finding that they are very safe. But, you know, there's different sort of things to – to look for if people are on injectable.

Dr. Bositis: Yeah. Thank you for – for sharing that, Carolyn. I think that one of the key points that we want to communicate here is that for the vast majority of people who are going to be using PrEP, any form of PrEP is going to be safe, and – and well tolerated. And that the other thing that I wanted to highlight here is that in the DISCOVER, in other PrEP trials that looked at side effects and toxicities of – of oral PrEP, even when safety signals were found, they were low and they were reversible. I think that's the really important thing. So, and this is the other thing that I think distinguishes it from – from the – the population of individuals who were targeted in that – in those lawsuits, those were people who were taking long term antiretroviral therapy who expected to be on that treatment for the rest of their lives.

Whereas PrEP is not necessarily something that somebody is going to be taking for the entirety of their lifetime, but only during periods of highest risk. And so, I think that it's important to note that when you're thinking about what is the real safety risk of this particular medication?

Mitigating/Avoiding Renal and Bone Safety Concerns

And so, we do know, however, that there are some people who may not be able to take F/TDF in particular because of underlying renal issues or because of underlying osteoporosis. And in those instances, we know that there are other options for – for individuals who do not have access to long-acting injectable PrEP. We can – we can think about whether or not they might be a good candidate for event-driven or 2-1-1 F/TDF. Similarly, these are the folks in whom F/TAF may actually be a really good option. And like I said, the long-acting injectables so far have not been found to raise any of these same, similar safety signals.

So, related to that, actually, Carolyn, I wanted to ask if, you know, we say that event-driven PrEP with F/TDF is one potential way to mitigate safety concerns for – for people that may have underlying renal or bone disease. What about event-driven F/TAF, do we have any data, or can we look forward to any data about event-driven F/TAF?

Dr. Chu: Yeah. Thanks for bringing that up, Chris. I mean, I think specifically referring to the F/TDF product. And you know, though that was the intervention that was studied in the first event-driven trials from France and also Canada, and so at this time we don't really have clinical data that yet can sort of give a, you know, that sort of certainty around F/TAF. But there is a trial that is actually enrolling.

So, if we have anyone today joining us from France or Thailand, there is actually a study that's called the SimpPrEP study, I believe, that is posted on clinicaltrials.gov. Certainly, anyone who's interested can look at what the eligibility criteria are going to be, but those investigators from ANRS are actually going to be looking at F/TAF for event-driven. And I think what their – the proposed schedule that they're going to be looking at is actually maybe 2-1-1.

I will say though that, and again, we might get to this when we talk about the challenges. So, even though, you know, at least in the US guidelines, you know, there are some folks who really make a point of saying it's F/TDF, at least our – our colleagues in Britain actually feel like there's very compelling sort of PK/PD data really looking at PBMC, so cellular levels of medication. Not – you know, they sort of put aside like, you know, tissue compartment, right? Because we're – we want to make sure that everyone sort of has the options that feel like there is going to, you know, will fit for their lives.

And our – the British guidelines don't seem to make a distinction actually between F/TDF or F/TAF, whether you're taking it daily or event-driven. So, that I think is extraordinarily compelling. I don't know what the US guidelines will look like in the future, but just to say, this is very much an active question that I – that I hope we get some answers to.

Myth 3: PrEP Doesn’t Work for Women

All right. So, as we go into myth three, let's dispel this myth, like right here and now, okay? We have, you know, gotten calls from people saying, oh, but I heard PrEP doesn't work for women, that, you know, it has to be taken with perfect adherence. Chris, what do you think?

Dr. Bositis: Yeah, that's a really good question. And I think I want to start my answer to that question by providing a little bit of historical context. I – the – I think this myth comes from the fact that there were negative PrEP trials where the - the population being studied was primarily cis women. So, the fem PrEP and the voice studies, for example, did not show any benefit to tenofovir-based PrEP in – in those populations.

The second – I think the second reason why this myth has been generated is because – because of data that was circulated early on looking at time to protection. And actually, I think we're going to talk about this question about time to protection a little bit later on – in this presentation, but really what they were looking at is not time to protection, but they were looking at time to maximum tissue levels. And when investigators have looked at that, it is true that the – that maximum tenofovir levels in the cervicovaginal tissue take about 21 days before you get there. And so, that's much longer than what we see for PBMCs or rectal tissue, which is – is closer to seven days.

And remember this is with daily dosing. Once – you know, one pill once every day which is important to remember because we're going to talk about, well, what if you use a double dose later on, does that make a difference? But I think the – the – there are two important rebuttals here to this myth. The first is that what we have learned over and over again is that PrEP, like any other medication, works when you take it. And we have seen through different analyses that when you factor in adherence and – and do analyses based on those who are consistently or even maybe not perfectly, but kind of more regularly taking their – their pre-exposure prophylaxis, that PrEP still works for cis women and frontal sex.

So, two studies to point out here, the first is related to F/TDF. And this is a – this is a pooled analysis done by Jeanne Marrazzo and colleagues that looked at a number of different PrEP trials. And what they – what – what they found was that in individuals who were taking – who were taking their pre-exposure prophylaxis with who had at least either high, which is defined as four to six doses per week or daily dosing that those individuals achieved levels of protection that were similar to what we've seen published in in other PrEP trials where the – the population study was – was primarily MSM. And so, we're talking about 90% or greater reductions in the likelihood of HIV transmission.

And so, I think it's really important to – to know that again, if somebody is taking their oral PrEP, it does work. And this is true for women as well for men. So, the second point that I wanted to make is that, you know, we were all really excited about the purpose study, not just because of it was analyzing the – the use of a novel injectable form of pre-exposure prophylaxis lenacapavir, but also because they enrolled in F/TAF arm for – so yeah, an F/TAF arm for cisgender women and analyzed the effect efficacy there.

And when the study was first published, it did not appear as though the women who were taking F/TAF achieved any significant protective benefit. However, again, what we have seen from a sub-analysis of those study data is that in women who are taking it at least two times a week or more, so not great adherence, but at least twice a week or more, that they also had a significant protection from – from becoming HIV infected.

So, I think all of this tells us that there's still a lot that we don't truly understand around the pharmacologic requirements of protection from – in cisgender women for tenofovir-containing PrEP, but as long as people are taking it, most of the time it should be effective. And so, that actually brings me to a question that I had for you, Carolyn. Since we are seeing that most of the time is probably good enough for all forms of oral PrEP, do you have any thoughts, are there any studies, or are there any data that suggest that event-driven PrEP may be an option for cis women or individuals having frontal sex?

On-Demand PrEP for Women

Dr. Chu: I would say unequivocally yes. And as I mentioned earlier, you know, we – there are some amazingly talented investigators that I think are just looking at this, you know, through a different lens, right? They're really relying on some PK and PD models, which have been informed by sort of what we're learning from the clinical trials. But, you know, there's a compelling argument to be made that actually we should just be looking at cells, right? PBMCs. I think we talked about that earlier. And so, I do think it's feasible to develop sort of an on-demand option. I think where things are now is that, you know, we don't quite know what the optimal dosing strategy might be. But is it possible? I think absolutely, yes.

And again, I'm hopeful that, you know, our guidelines, you know, in the US will – will be updated because we are seeing that actually there are some groups that have already started to weave in content around this in their guidelines. So, for example, here the New York State Department of Health actually, you know, over the last year they have incorporated some information about this option. And so, if folks go to HIV guidelines.org, that's the New York State DOH, they actually say that 2-1-1-1 – but again, with F/TDF could be an option for people who are having vaginal exposures, who either just maybe daily PrEP isn't going to work for them or also just aren't really interested in the injectable PrEP. And, you know, we know that it's just good to have multiple options but we also want patients to feel confident that, you know, the option that they choose is going to work for them. Right?

And so, I do hope that we'll have, you know, clearer guidance on sort of what – what this dosing strategy might look like. We do know that our colleagues in Britain, when they updated their guidelines, at least on the last iteration, had felt more confident in actually 2:7. And so, what that denotes is, again, this double dose getting protective levels up very quickly and then taking one pill once a day for – for seven days. And again, just to flag that our British colleagues don't seem to sort of differentiate really between F/TDF and F/TAF. And so, I think it's – it's – it's nice to have options I think as providers, because we all know the real-world does not always follow strictly by the guidelines and people are going to see, you know, sort of these edge cases, right? That we need to figure out what – what can we be offering our patients?

Dr. Bositis: Yeah, 100%.

Interest in Injectable PrEP Among Women

Dr. Bositis: We do have one more point that I wanted to make. And it actually picks up nicely from – from your last statement, Carolyn, which is that we really want people to have options, right? And I think that while it's important to emphasize that all forms are effective – all forms of PrEP are effective when taken as prescribed, one of the key lessons that we've learned in many PrEP studies, particularly those that have focused on cisgender women, is that options really, really matter. I'm not going to talk about the Dapivirine Ring and the whole story behind that. There are a lot of people here in the US who feel like we have been slighted because the FDA refused to consider Dapivirine for as an option for women, because many women actually prefer that as an option. But I do want to mention the fact that – that injectable PrEP is a – is an option for women as well, both CAB and LEN.

And part of the reason that I wanted to – to highlight that is because there have been a couple of studies that have looked at interest in PrEP among cisgender women. And specifically looking at what form of PrEP they would be interested in, and what we've seen in – in a couple of different studies one of which we have data for shown here, is that there is a fairly high demand for injectable PrEP among cisgender women.

It's interesting to note that when they did a qualitative interviews, they found that there were really very specific subpopulations of cis women that – identified as being potentially those who could most benefit from long-acting PrEP. Those included young people, women with childcare responsibilities, people with adherence issues related to pill taking, people with multiple sex partners and those facing issues of confidentiality or those just with structural insecurity around homelessness and other issues that might make it difficult for them to store or keep oral PrEP.

Similarly, when women who inject drugs were surveyed, a high proportion of them almost two thirds indicated that they would be interested in – in long-acting injectable PrEP, as opposed to just about 20% that expressed an interest in oral PrEP. And again, not to say that oral PrEP is – is bad but just to emphasize that – that options are really important.

Challenges and Controversies

Okay. So, we're going to move on to challenges and controversies.

Time On, Time Off, and Missed Doses: When to Consider PrEP to PEP and PEP to PrEP 

So, Carolyn, do you want to lead us here?

Dr. Chu: Sure. Yeah. Thanks. And I think, you know, we're – we're – we have so many options now and it's amazing. But also, having many options also leads to more questions, right? And I think that it's a challenge because you know all the clinical studies or even the sort of PK studies, you know, they're – they're getting at the science in slightly different ways. But ultimately for – for guidelines, folks, and we know this is not an easy task, I mean, they really have to look at the evidence, right? To be able to come up with, you know, they believe is sort of the best – best guidance and also can help inform some – some of the best practices.

So, we've organized this particular challenge into sort of a couple buckets. New starts, so people who are starting PrEP for the first time, and this can be oral, this can be long-acting injectable. We also want to sort of briefly touch on, you know, the questions that come up if people are transitioning from different – different PrEP products, if they're, you know, regardless of whether they're going from oral to injectable or the other way, or even we do get questions about, okay, this person's been on PrEP, maybe they forgot a dose or two this week, actually, you know, do I need to also be talking with them about post-exposure prophylaxis if they've had an exposure of concern?

The guidelines sort of get at this issue in different ways. And some guidelines don't have a clear answer, but, you know, these are certainly the calls that we know people are seeing in their practices. So, Chris, what do you think about new starts for oral PrEP? We've already talked about like double dosing, like what are your thoughts on that?

Dr. Bositis: Yeah, that's a great question. I think – I think interest around this question really stems from that issue that we brought up earlier, which is how long does somebody actually have to be taking PrEP before they are fully protected? Right? And the answer to that question is we really actually just don't know. And so, historically we've looked for other markers to help guide us as to when that might be. And we have historically looked at constant – maximum concentration of the – the – the – the drug in the tissue component of concern. And – but as we've seen, there are – you know, the time frame to maximum – maximum drug level in those compartments is highly variable. And so, that has raised the question, but yet the PrEP studies have actually all shown great benefit. And so, the question is, well, is that really the – the – the right marker for – for protection? Should be – should we be looking at PBMCs instead?

And regardless, you know, can we just play it safe and give everybody a double dose of their oral – of their oral PrEP, whether that's F/TDF or F/TAF, and will that help people achieve higher drug levels faster? And so, I think, you know, I want to be clear, we don't – we don't know clinically whether or not this is really – whether or not this matters a lot, but we do have data, both PK and PD data that indicate that taking a double dose of your oral PrEP, whether it's F/TAF or F/TDF really can help provide protection more – more quickly.

So, the next controversy that we wanted to address is around PrEP testing and how to monitor people on PrEP. And as many people are aware, the guidelines currently say that – the CDC guidelines currently say that anybody who has had exposure to either oral or injectable PrEP recently should have both an HIV antigen antibody test and an HIV NAT done as part of their PrEP monitoring. What do you think about that, Carolyn? Do you have any questions or concerns about that monitoring approach?

Dr. Chu: Well, yeah, I mean, I think pretty much as soon as those guidelines were released here in the US, we started getting calls on the PrEP line. Just saying like this feels extra. We don't know if we can actually implement it in our practice. And so, you know, do we need to rethink everything? And these recommendations were applied for, you know, both the oral and the injectable. And, you know, there had been a lot of focus, I think, on LA CAB because, you know, those early cases of, you know, possible delayed, you know, detection.

But, you know, ultimately, I think that – that leads to some real tensions on the ground because we don't want PrEP programs to feel like they have to fold if they can't do all of, you know, the recommended testing. And I think what we're seeing now is actually maybe a shift back towards just relying on an antigen antibody primarily for both PrEP continuation, so meaning monitoring and follow up visits, but also, we know that, you know, you can rely on a fourth gen, and if you can get a viral load too at the PrEP initiation, great. But I think the role that the viral load, you know, may or may not be playing, I think we're – we're seeing some kind of like de-emphasis on that. And I think that's the right way to go.

And so, I did notice that there was a question that we got around sort of, you know, so what's – you know, how do we – how do we think through, you know, what this ideal screening test is? I think certainly fourth gen, most programs seem to be able to have that, at least in the US. And then the question is, okay, well, if you have an ability to do a viral load, you have to be really thoughtful about who – who maybe you're going to also order that test for. But also, it might be worth building some screening questions into your – your sort of workflows, just, you know, to look or to ask folks if they remember having any kind of flu like illness.

And so, I think this is an evolving area, but my hope is that the guidelines will start to sort of streamline, but also harmonize, you know, between settings and countries.

What’s Working and What’s on the Horizon

Dr. Bositis: And so, I – yeah, I think we want to end with just a brief discussion about what we've seen has worked in practice and what we see coming on the horizon, and yeah.

So, Carolyn, in your experience, what are some of the things that have been successful in – in PrEP programs that you've seen that have been effective at, you know, at incorporating a large percentage of – of the community and ensuring that – that everybody who wants PrEP is – has access to it?

Dr. Chu: Well, I think it comes down to making friends. We know that PrEP navigators can play extremely important roles, sort of almost kind of bridging, you know, the clinic personnel, but also community and patients and just being able to help develop some outreach strategies, helping people navigate benefits. I'll just be frank, right? These injectables cost a lot of money. Not everybody has coverage that's going to, you know, take all the cost off of the shoulders of the patient. And so, navigators, I think, play a huge role in closing some of the gaps around access. But also, we know of programs that their navigators are also checking in with patients about adherence. Right?

So, you know, we saw you yesterday for your PrEP. You know, you got the prescription. Have you been able to fill it yet or? Just like doing some troubleshooting so that patients can get on to the PrEP that they want and can also stay on the PrEP that they want? I think one thing that's very exciting as well as, you know, when I talk about making friends, like get to know your pharmacy partners, right? Pharmacists can play huge roles in just helping to navigate benefits, but also talking with patients, you know, providing information about PrEP because we also know that patients really trust, I think, you know, their pharmacists in a way that – or, you know, feel comfortable asking questions in a way that they might not in an exam room. And so I think the – the case has been made in many, many analyses that pharmacists are absolutely integral for rolling out PrEP.

Dr. Bositis: Awesome. And in terms of future – future options, what's on the horizon? Any highlights that you want to – that you want to mention here?

Dr. Chu: Well, I – I think that we're learning about how to implement long acting. Hopefully, we'll get some questions, but the two long-acting products that at least are available to us here in the US, they're both highly efficacious. And so, I think at this point, the decision making about, you know, choosing one over the other really is coming down to understanding, you know, what the person is looking for. And then maybe also going into details about, okay, well, one is an intramuscular shot, right? And the recommended area is in the buttocks, but then the other is a subcutaneous and the recommended area is the abdomen.

But we know that maybe people might not love the idea of having a med in their abdomen. And so, they – you know, we're looking at different alternative injection sites. And so, we also know that there is an active research pipeline looking at longer interval dosing. So, for the products that we have now, can we actually space out from Q6 to Q12.

Dr. Bositis: Q12. Right.

Dr. Chu: Right. For the every two-month product, can we go to every four? So, that is all hugely exciting. And I think we need to learn as we're going along right now with what's – what's happening.

Dr. Bositis: All right. Thank you so much. And so, we're going to move to questions now.

And so, looking – looking through the – the questions that we've received so far. So, okay, let's start with this question.

What is the ideal time to screen for HIV prior to initiating PrEP? I keep getting referrals for people who are screened a few months prior. And people give pushback when they – when told they need to be rescreened before they can initiate. I use one week is that appropriate.

Dr. Chu: Sure, I can – I can try to kick off with my thoughts. So, I think that this is pretty common. And I think that the testing approach might be really different if you're doing oral PrEP because I think, you know, there's – there's definitely a push for rapid PrEP starts because there's a need. And so, if – if someone reports a negative screen a couple months ago and no concerning symptoms I – you know, I will feel comfortable drawing the blood and offering someone a PrEP prescription that they can take. And I want to make sure that I have their contact information because if there is a surprise, and actually if my test comes back with a reactive, I want to make sure that I can call someone back right away because I wouldn't want them to, you know, be on their oral PrEP for too long before we can, you know, confirm is this a true infection or not?

For people who are coming in and wanting to start the injectable, you know, I don't have a way to do same day injectable right now. And so, there's going to be some – you know, it just – you know, isn't going to be feasible to do same day injectable PrEP. And so, likely that person is going to come back and, you know, again, if we need to do further testing, we will. But I think one week sounds – you know, that seven-day window certainly what the CDC guidelines recommend.

Dr. Bositis: Yeah. And – and I would say that there are places I think that are doing same day injectable. And I think that's – I think you can do it; you can do it. I think that if you have a negative rapid antigen antibody test or even just a negative rapid test, you can give that dose as long as you've sent the lab based antigen antibody test and you have a way of contacting the individual to make sure that you can connect with them should there be a surprise on the test results.

A related question, Carolyn, is, what is the appropriate screening and follow up testing, especially when the initial testing did not follow recommended algorithms? So, somebody gets started on PrEP, but they maybe didn't have the correct baseline testing done.

Dr. Chu: Okay. Yeah, that's a great question. I mean, there are definitely some folks who, if they're starting people on oral PrEP, they'll actually have the patient come back in a month and they'll use that month, you know, visit to – to do the tests. I think what the scenario that we're trying to avoid is having people be on oral PrEP for very long periods of time with undiagnosed HIV. And so, if that follow up, you know, at one month sounds feasible to your clinic, fine. If you can do it even sooner at two weeks, that's fine too. I think we just don't want to see people going months and months without having the follow up testing.

And so, in terms of follow up intervals, you know, that's going to differ depending on whether someone has been on oral or injectable PrEP. And so, again, you know, take home is, you know, absolutely do that fourth gen for everybody if you can. And then for – for, you know, injectable PrEP, for example, if you want to do that viral load on top, you certainly could. And so, every program is going to be slightly different, but I think the point is to, you know, sort of bake it into your – your routine follow up.

Dr. Bositis: Okay. And then related to that, Carolyn, for people who are on injectable PrEP, what do you do for follow-up testing? Do you do a rapid test or a lab-based test before the injection?

Dr. Chu: Well, in my – in my clinic, we do not have the ability to offer the point of care sort of, you know, real rapid. But, you know, if we're drawing blood, then that comes back from our lab pretty quickly. We know that there are some mobile and outreach programs that do rely on rapid, and I – and I think it's fine. Some places even do two rapids just to have sort of that backup. So, I definitely think it can be done ultimately. Just tell everyone know what test you're using so that you can sort of interpret it correctly and depending on the clinical context.

So, tell us what you're hearing about alternative injection sites for lenacapavir. And then are we getting calls or are you hearing about people who have leakage after administration?

Dr. Bositis: Yeah. Great question. So, in terms of alternative injection sites, I think this is an area of active investigation. For – for cabotegravir, there was actually an interesting analysis that looked at injecting cabotegravir in the thigh. The results of which were – were presented at [inaudible] a couple of years back. And it works, the PK data on the – the thigh – the thigh muscle injection were – were fine, but it was really painful. And so, in practice, there are not many people who are doing that just because of the discomfort that's associated with it.

With lenacapavir, again, at this point in time, this is more of an investigational site where we don't yet have great data, at least none that I've seen. Carolyn, have you seen any data on thigh injections of len?

Dr. Chu: Well, I think there's a little bit, and the little bit that we have seem like it might be okay. There are some programs that have heard from their patients that the abdomen is just too uncomfortable. So, they do offer as an alternate. But again, with all the caveats, like you were saying, like, it's not the recommended, you know, area.

Dr. Bositis: Right. And then leaking. Yeah, leaking, we get a lot of questions about leaking on – on the lines. And the short answer is, we don't know exactly how much leaking is too much leaking. And when you need to redose somebody, the manufacturer has given some guidelines that suggest that if you soak through more than one, two by two gauze and a band aid, then that suggests that you probably should redose.

But, you know, again, it can – over what time frame is that leakage allowed? How much leakage is normal? Those are – those are questions that we're – we're still trying to sort out. And the other thing that I'll say is that – that it – it is not uncommon. It's actually very, very common to have some leakage. And it's just when it's – it's a large amount that you need to be concerned and consider potential – potential redosing.

Dr. Chu: Yeah. And I think the other point that is worth mentioning here is that, you know, we also want to like, think, as you know, from a prevention standpoint, like, are there things that we can be training injectors on to like avoid, you know, significant amounts of leakage. And I think there – there is. I mean, it comes down to, you know, proper injection technique. We've heard that programs say they have a much better experience if they're icing the area, you know, for several minutes. And – and for the lenacapavir product, I mean, the manufacturer does have very explicit instructions on sort of what that angle is, you know, should be for the needle and then also injecting it slowly.

I mean, it's a pretty thick, viscous product. And so, it – it will naturally feel probably like a – like a slow, you know, sort of push. But we really want to make sure that nurses or whoever's, you know, doing the injections in your setting is doing it appropriately and not – not rushing it. Because, you know, it's the medication has to sort of stick in that – in that tract and then you're covering it and telling people sort of, okay, aftercare, you know, don't go exercising, don't massage that area too vigorously, just leave it alone. But let us know if you're noticing – noticing anything.

Dr. Bositis: Okay? And so, I want to make sure that we address the – the – this last bucket of questions that seem to be mostly related to counselling and how to create a safe space to talk about PrEP, whether that's in the – whether you're a clinical pharmacist or in the clinic. How do you have conversations with people about PrEP that – that promotes a sense of safety and honesty, and how do you do so in a way that does not – that does not unintentionally promote stigma of any kind? Carolyn, do you have any – any thoughts about that? Any advice?

Dr. Chu: You know, I think it does come down to sort of creating that – that safe environment. And I think that, you know, we are trying to build relationships, right? Like it might not come up at the first visit and I think it's okay, but over time, as patients feel comfortable or they know that, oh, you know what? You're someone I can talk to about HIV prevention and PrEP. I think, you know, it's – it's about sort of laying – laying that foundation. And also, you know, trusting that patients sort of know their lives much better than we might, you know, ever find out. And things – things change, like PrEP use is really dynamic. As you were saying earlier, sometimes people might be more interested in PrEP than at other times. And that is – that is totally okay.

Dr. Bositis: Yeah. And I think there are a couple of – of questions that we – that we recommend that are open-ended that are non-stigmatizing. Questions like, would you like to learn more about medications that can prevent HIV or how – how do you think your sex life would improve if you didn't have to worry about HIV? Questions like that can be helpful in initiating the conversation around PrEP. And as Carolyn said, it can take time, it can take time to – to get to the point where you and the patient feel comfortable having honest conversations like that.

The other thing that I would say is that if somebody asks for PrEP, you don't need to know the reason why they want it. You don't necessarily need to know the exposure route that – that would make them a candidate for PrEP, so to speak. Anybody who asks for PrEP should – should be offered it and reassured that this is a good and healthy thing as they seek to take control of their bodies and, do what they need to do to lower their risk of – of acquiring HIV.

Dr. Chu: Thanks, Chris.