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Mhm. My wife and that's uh, all right. Hi, everyone. Thank you for coming to our talk today on complex prep with Erica Pool. Um, despite what it says underneath my face, my name is actually Emma Cartner. I'm one of the operations called Native Stash. Um, yeah, because I thank you all for coming. So we've got this great talk about complex prep and research into prep with doctor Pool. So it's a bit about Doctor Pool. She has a specialist registrar in gum at the Mortar Market Clinic Center in London, and an academic clinical fellow at UCL. She trained in medicine in Leeds and did her master's in public health and it leads to, she has done, had clinical academic post in York, Brighton in London and has a wide range of experience in research on HIV, prep ST I say great person to this talk. She's also been involved in writing the guidelines for opportunistic infections and prep and very soon we'll be starting a phd on HIV HIV prevention in people experiencing homelessness. Um, so Erica is going to do her talk and then if you have any questions, if you put them into the chat and we can go through them at the end. Thanks very much. Maybe two a day. Great. Thank you so much, Emma. That's great. Um It's been just going to my next slide. Yeah. So like I'm a says, my name's Erica. I'm a registrar down at most of the market. And today we're gonna talk a little bit about prep about the complex prep clinic. Um I'm going to talk through some cases and a little bit about future research. Next, please. Thanks. So very briefly. Just cover the basics just to make sure we're all on the same page because I know people have got different backgrounds. Um, so prep or HIV, pre exposure prophylaxis is a medication taken by people who are HIV, negative to prevent them getting HIV. And we know it's extremely effective reducing the chance of getting HIV, between 86 97% when it's taken correctly. Um, the graph on the top right is from the prep impact trial and it shows that HIV incidents was 87% lower in people who were taking, uh, prep compared to people who weren't taking prep and that's for about 20,000 people. Um, and we also that perhaps really safe, including in long term use. We've had people on prep for well over a decade now. Um, so that's a really positive thing. Um, there are three main drugs that have been proven in trials to be kind of options for prep, although we don't quite have access to all of them that yet in the UK. So the first and by commonly, the most far, widely used drug globally as prep is Privada is the brand name. It's now off patent. So we don't need, we can use generics, nice and cheap. Um and that contains, it's one pill containing two drugs. So it's enough of the dice, approximal fumarate or TDF and Emtricitabine FTC. Um So TDF FTC can be taken um as a tablet daily or event based which means before and after sex um to prevent HIV. So that's one option. And it's the thing that's most commonly used in the UK and globally as prep. The next medication is something called Descovy or turn off of it. Alafenamide with Emtricitabine. So it's a slightly different formulation of that. Enough of it. It's useful because you can use it in people who've got reduced renal function. Um But it's only licensed for people um who are men who have sex with men and trans women. And it's only licensed for use daily primarily. That's just because there's only one trial of Descovy and that's how they dosed it and that's who they studied. It probably can be used more widely than that, but that's all. And the only licensed ways to use it. Um And then thirdly, um the third medication that's been shown to be effective as prep um is long acting capita graffiti. So that's um an integrase inhibitor which is given as an injection, um just once every eight weeks. Um We don't have a long acting Cabotegravir um, here yet in the UK. Um partly because they've not got their license yet, but also because it's been priced, um, well above 10,000 lbs per person per year where as generic Truvada costs about 100 and 50 lbs per person per year. So I think unless they saw the pricing gout is gonna be quite tricky to use that widely um here. Um And also I just wanted to acknowledge um the amazing work of the activist community which you can see on the bottom of the screen without whom we would never have as excellent and as widespread perhaps prep access as we do here in the UK next slide. So a bit of a timeline of prep um because I really feel like I've kind of grown up alongside prep in terms of my medical career. So it was just 2010. So just uh 13 years ago that the first study um was published showing that prep worked. That was the I Prick study and it showed for the first time that prep was effective in preventing HIV. And this was a study in men who have sex with men and trans women. And it was using um the TDF FTC or Truvada drugs. There had been some prep studies done earlier um but they hadn't um shown that prep worked primarily because um adherence was quite poor and for lots of different reasons, people weren't really taking the meds. So 2010 was the first time we had a study showing this is prep and prep works. Um That study was in North America. So a couple of years later, in 2012, we had the first UK prep study. So it was called Proud and it opened here just over 10 years ago. Um And also that year, there was a study from Uganda and Kenya, the partners prep study that showed for the first time that prep work and heterosexual people. A couple of years later in 2015, Proud reported and showed the best results that we had that so far that prep reduce the chance of getting HIV by 86%. And Proud was a study of daily preps that was really um massive news. The same year, the epic a study um reported exactly the same percentage, 86% reduced chance of getting HIV for event based dosing preps that's prep before and after sex. Um And in the same year, um the community organizations I want prep now and perhaps the launch which have been massive in driving forward knowledge and access to prep. Back in 2015, we have by that point kind of five years of data showing this as prep. It works, it's extremely effective. Um But if you wanted to prep in the UK in Proud there was about 500 places across the entire country for prep. Um And that was the only way of accessing prep through clinical trials at that point. So what I want prep now did was they made sexual health D I Y they showed people how and where to buy an import prep online. Um And we, our sexual health clinicians supported patient's in doing that um in clinic and gum clinic at that point, what our job was in terms of prep was to provide prep care, to do the monitoring, to do all the tests and to do everything except the prescription and then patient's would go off and buy their own preps where I want prep. Now, um looking back now for a place where I'm prescribing prep every single day in clinic, it seems extraordinary. Um That was what we were doing back then. Um In 2017, I think we're all hoping that by then, we would have got prep on the NHS, but it was still at that point under patent, the prices were really high. Um So what they did instead was this prep impact trial um where they made prep available to originally was 20,000 increase to 30,000 people through the prep impact trial primarily as a means of accessing prep at cheaper prices than it would have been through usual prescriptions. Um as well as cutting some uh interesting data. Um In 2020 we finally got prep on the NHS because by that point, it go off patent and so the price would come right down. Um And also in that year, the discover trial reported, which showed us that um it's not a bit alafenamide this over form of Tenofovir that you can use with people who've got kidney or bone problems. Um So the discover trial reported showing that Taf prep was equally effective as TDF preps. That was really fantastic um in 2021. So a couple of years ago, now the studies of long acting cabotegravir, so that injectable form of prep reported and that they showed to be even more effective. So the most effective form of prep yet. So that's the kind of prep research timeline and where we are now. Um next L E Emma and it kind of correlates with my medical career. Um and that's kind of why I feel such a relationship with. Perhaps I feel like I've kind of grown up alongside it as, as I've been qualified and as my practices developed. Um and for me, that's been one of the nicest things about gum training is that kind of rapid change and um innovation and all the different things for me to see um kind of research come alive and come into my usual practice. So in 2010, when this I prick study was reported, I was in my final year of med school and I have to say it passed me by, I was just stuck in my books, revising for finals. Um But by 2012 and the time of the Proud study opening, by this point, I was an academic f two up in your. Um, and I was actually working in a garment HIV trials unit in York. Um And in fact, worked on the Proud study. So we only had a very small number of patient's up in York at that time in the study. Um But that was my introduction to prep where I first learned about it. Um After F two, I went off and did my master's in public Health at London School of Hygiene, tropical Medicine. And one of my lecturers there was will know Thailand who the next year launched prep stir. So I kind of followed um what will was doing and followed the events of prep stir along the way. Um and kept up my kind of knowledge and learning in that way. And I went off and after my masters, I did um what was called medical training. Now, I M T I did mind down in Brighton um and kept in touch with the gun clinic and all the changes there. Um After CMT I came up to U C L and got a research fellow job. And I started about eight weeks before impact opened. And my main job that year um was to help run the Impact trial and set up the clinic sites and recruit hundreds of patient's and start them on prep. So I very quickly got very familiar with all of the clinical um uh you know, processes and everything around prep. Um And I then the year after, took up my gum training number here. So I started my gum training here in Baltimore market. Um I joined the prep guideline writing group because by then I was um prep was becoming a bit of a one of my favorite topics. So I joined the guideline writing group. And again, I think that's something really positive as a gum trainee is that I found that there's lots of opportunities for trainees with things like, um, getting involved in writing guidelines and other things. So that was really positive experience and, um, something I learned a lot from, um, and as Emma said, um, in a couple of months, actually, in a month and a half, I'm about to start my phd. Um, unsurprisingly with everything we've talked about looking at prep, I'm looking at HIV prevention, um, for people experiencing homelessness. So kind of looking at the way everything looks right now. It might look like I always had this Grandmaster plan, but I absolutely didn't. Um, I think at every, every point I have just been looking towards, what's the next step, what's the next thing that's interesting to me? And it's only really now looking back, um, it kind of feels like it was always going to be about prep. Um Next, please. Fine. So what is the complex prep clinic? Um It essentially is something that I've a service that I've helped set up here in more to the market. Um Now, of course, most prep isn't that complicated. It's not that medically complex. And in fact, demystifying and kind of simplifying prep care is really important and way of um kind of widening and increasing access. But there are some cases where there's a bit more complicated and that's why we have the complex prep clinic. Um It's been going Atwater market for just over a year now. And we did a brief um kind of evaluation on our first six months. And in the first six months, we saw 100 and 16 complex prep clinic patient's, we've got about four or 5000 general prep patient's. Um So that represents about 2% of our kind of usual prep users needing extra or more complex care, which fits about with um for example, the numbers over at Dean Street. Um and what are we seeing? The vast majority of things that we're seeing are renal cases? So perhaps the drugs is metabolized or broken down by the kidneys. Um And so we need to be thinking about renal function, ensuring that kidneys are working well in order to prescribe prep safely. So, renal function stuff is by far and away, the most of what we're seeing. Um the next things we're seeing things like side effects possible allergies, um queries about pharmacology and then a whole bunch of other things. Um Next, please. So we're going to talk through some cases and I want to be really clear that these are imaginary cases. They're not um individual patient's. Um uh but so they're just cases that I have invented. Next. So case one. So this is a 49 year old cis gender gay man who's born in China. Um And he's been using daily prep since 2018 and he's referred over to my complex prep clinic due to declining renal function. Next. So of course, whenever we're thinking about renal function, we want to be thinking about trends and we can see here it's a nice trends over time um with essentially a gradually reducing EGFR starting at a slightly late baseline and now where we are in 2023 we've got an EGFR of 55 a little bit of protein urea, but that's not too bad. Um I'd also be taking a really thorough history thinking about his past medical history. Um and this patient has got a background of hypertension. He's got Hepatitis B with cirrhosis. Um and he's got a chronic knee injury from some sports. So he takes a day to day, he takes some Ramipril, he takes his prep um and he takes diclofenac. Uh Next, please. So what do we know about prep and kidney function? We've got really good data. Um Essentially for most people prep will have minimal kind of clinically significant impact on the kidney. So, yes, it's um really metabolized. But the average change to creatinine clearance for your average prep user is about 1 to 2% per year on prep. So if you're starting off with an EGFR, um it's about 80 or 90 then even if you take prep for a decade, it's not, it's still going to be 70 or 80 and that's perfectly fine. Um And the important thing that we know is that um any changes to renal function completely reversible. So when you stop prep, your kidneys, go back to their pre prep function, which is great. Um The predictors of people having slightly worse and renal function were being aged over 40 initiation or having a lower craning clearance at baseline. So those are things to think about and also definitely reported in the literature is Fanconi syndrome, um which is a kind of kidney tubule disorder and that's quoted in the literature is happening in about one in 10,000, 1000 cases. Now, we've got 5000 crack users here and we've probably had more over the last kind of five or 10 years and I'm not aware of any cases of fanconi. So I suspect it's much rarer than the literature says. But um it's something to be aware of. And importantly, um the Truvada to offer disproxil FTC form of prep, it's only licensed down to a credit clearance or EGFR of 60. Uh Next please. Now, also importantly, in this case, um important to think about his other comorbidities. So this person has hypertension and they're using daily nonsteroidal. So they suppose risk factors for CKD which might explain his slightly more rapid decline, but he's also got Hepatitis B. Um and TDF that cannot have a component of prep um is licenses prep, but it's also used as Hepatitis B treatment and his HIV treatment. So we need to be mindful for prep users who also have Hepatitis B. That the not for that we're prescribing is doing two things. It's preventing HIV, but it's also treating the Hepatitis B. Now for people with HEP B who have cirrhosis, if they stop treatment, you can get Hepatitis B rebound flare. So it's really important to be mindful. Um in these kind of cases that you don't want to be um inducing ahead be flare where you know, you get an A L T in the 2345 hundred's. Um and can be quite serious. And so because of that event based dosage just isn't an option because you'd be starting stopping prep and you might be at risk of flare kind of repeatedly. Um Next, please. So in this case, what we do is well, with everything we have to talk about with his HEP B, he definitely used to stay on some daily to enough of it for both prep and for Hepatitis B treatment and we'd be linking up definitely with the Hepatitis team and here at more to market our gum service runs um Hepatitis Clinic as well. So that would be really easy for us to do here. Um And we'd be switching him to taf, so that's enough that alafenamide the Descovy form of prep with lots of renal monitoring. Um And we might think about referring him onto renal. Um So it's great to have that option of an alternative prep drug hair next, please. So our next case is a 29 year old woman. She's got a history of hypothyroidism. Um And she's had everyone y gastric bypass. Uh She takes medication, she takes omeprazole um multivitamins, which most people do after bariatric surgery. Um and she takes levothyroxine and she's got a Mirena coil in city. So she wants to start prep. Um, but she has been referred to the complex prep clinic over to me because she's worried about the impact of her surgery and is she able to take prep next. So, a real my gastric bypass um, rule and wise are a type of bariatric surgery. Um, and essentially what they involve is they make a, a little pouch of the stomach. So just the top bit of the stomach is formed into a pouch and then the entire gi tract is Replumbed. So that pouch is plumbed directly into the distal Djedje numb. So it completely bypasses the gi codeinum, the ileum and most of the Jejunum. So you miss out most of the small intestine. Um so food or anything going into the mouth, like drugs, um goes into the mouth, esophagus, stomach and then straight to Jejunum and then onto large intestine. Um So of course, that can impact pharmacology, you know, it's really effective as weight loss, but definitely impacts pharmacology to. Um so it reduces gastric motility. Um It reduces gastric volume, obviously get an increased Ph which can impact some medication um and a massively decreased surface area of the gi tract which can impact absorption next. So really unhelpful, it's enough of it. And emtricitabine, both components of prep are absorbed in the duodenum, which after everyone, why is just completely bypassed? Um um there's a little bit of data, it's not great, but there is some limited data, um which tells us that concentrations of enough of it after everyone like gastric bypass can be reduced back to 40%. So, um it's a really significant drug kind of drug concentration changes next. So in this case, what we definitely want to be doing is talking with our pharmacist um with the M D T and checking in on the Liverpool HIV drug interactions website, which really helpfully has a whole section on the impact of bariatric surgery on antiretrovirals and preps that's really helpful. Um And what that tells us is to that um absorption of prep is increased after bariatric surgery if you take it with food. So we definitely wanting patients to take it with food. I think at the moment, it's an area of really limited data and we just don't have that much knowledge. So I think we definitely be advising um this patient take prep daily and we wouldn't want to think about event based in this case because um, we just can't be confident that we're going to get therapeutic range quickly. Um And we would also be doing some therapeutic drug monitoring. So doing some um special blood tests before and after a dose of prep was taken to measure the concentration of prep um in their blood and to help us understand whether prep was in therapeutic range for them. Um And like I said, there's just really not much data at all out at the moment. So I'm going to give a little plug to watch this space because there's some more data coming. Um That's our clinic and some other clinics have contributed to that should be being presented at bash this year. Um On exactly this question. Next and final case. Um is a 35 year old trans man. Um He's got a regular male partner who's living with HIV and has a detectable viral load I E A high viral load. Um That's really important. I'm sure most of you already aware that you equals you. So undetectable equals un transmittable. So that means that for people who have a close relationship with a person who's living with HIV, where they have an undetectable viral load, then there's no chance of person on HIV through sex in this way. And so in that scenario, perhaps not needed, but in the case that we're talking about, um, where this person's regular partner has a high viral load of detectable viral load. That's why prep is needed here. So, um, this person's got a past medical history of asthma and in terms of medication, they take testosterone patches and salbutamol. And the reason for the referral is that they're worried about prep and tea and drug interactions and he's also worried about his partner's recent blood tests. Next. Um So we, one thing we can be really reassuring about is that there are no drug interactions between gender affirming hormones and perhaps that's something really important to be confident and clear about with patient's. Um And I think especially important because many trans and non binary people will, might worry about drug interactions and often will prioritize their gender affirming care of other care. So it's important to be clear. Um people using gender affirming hormones that we can be really confident that we're not worried prep is not going to impact the positive benefits they receive um from their gender affirming hormones. Um just being transit prep, prep, use in other ways while the choice of daily or event based um just really depends on the type of sex and the partners, gender. So event based dosing is only used for people whose risk or exposures are only through anal sex with this person is having sex in other ways that aren't anal sex, then they'd have to be taking prep daily for it to be working. But that's the main impact. Uh Next. Now, thinking about his partner's recent blood test. So we know that his partner has been struggling with their HIV treatment and medication for many years. And some recent blood tests have come back showing that his partners HIV has shown drug resistance to emtricitabine. Now, the medication that we used as prep is Tenofovir with emtricitabine. So what does this mean for our patient's prep use? Well, the first thing to say is again, this really limited data in terms of prep efficacy and drug resistance. All of the our CTS have been done for considering just the person using prep, considering them at a general community risk of HIV. There haven't ever been any paired studies where we um have kind of data or resistance testing of um people's partners who are HIV positive and detectable. Um There are some animal levels where they have essentially exposed monkeys too. Uh HIV viruses including virus with drug resistance and then given the monkeys prep, prep. Um but they're quite limited to. Um and there have been some trials of to not have a monotherapy prep, which showed some efficacy, but it was much less than with combined and Tenofovir with Emtricitabine prep. So that kind of informed what we might think about doing in this case next. So what would we do in this case? We definitely want to be discussing all the options really clearly with the patient as well as with our wider team, are kind of pharmacy and R N D T. Um and it definitely could be an option for him to consider um continuing with combinations enough of it and Emtricitabine prep. But I think we have to be mindful that actually because of his partners, emtricitabine resistance, although he's taking two drugs, the it might well be that only one of them is functional. And really what we've got here is kind of functional to offer him on a therapy. And so that does mean that the efficacy could well be reduced. And it's important that he's aware of that. Um and important also of course, to be considering and remembering all the kind of wider HIV prevention methods and making sure that they're really optimized in terms of regular testing, in terms of condoms. If that's something that works for them and remembering about you equals you and if that if his partner becomes undetectable next. Okay. So moving on to a little bit about prep research next. So the main um kind of some of the main areas of prep research is thinking about new drugs um and partly that includes totally novel um drugs being developed. So things in the pipeline are things like broadly neutralizing antibodies as well as drugs like is lateral for. Although there have been some issues just more recently with side effects and some of these lateral trials. Um so those are both new compounds which currently are not being used in kind of routine care. But there's also um studies repurposing drugs that we currently use as HIV treatment such as bictegravir and elvitegravir and asking the question. Well, if, if uh other HIV drugs treatment, drugs work as prep, could these drugs work as prep? Um So that is some of the kind of one aspect of the research is about new drugs. Um And I think it's important to kind of that we are that we do get a few more options because sometimes, um maybe because of kidney function or because of a drug interaction or other reason, the current options that we have. Um uh you know, I think more options will be quite helpful in some cases. Uh Next, the other kind of big area of research is about different delivery models. So thinking about vaginal rings, thinking about patches about long acting uh subdermal implants, long acting injectables and perhaps long acting modified release oral therapy. I think really what this reminds us all instantly of is all the different choices that we have in contraception. You know, I think it would feel really bizarre to sit in clinic and say, um, two people. Yeah, you've just got to use condoms. We've just got to use condoms with this one pill. We've got to replace and contraception. Now where we've got loads of different options, we've got coils, implants, injectables, lots of different things. And I think it's really positive that we can be hopefully getting too a similar place with prep, just recognizing the different modes and different methods to different people in the different points in their lives. And I think one of the really positive things about all these different methods that are being studied here are they kind of facilitate less frequent dosing. So it doesn't have to be something that's remembered every day. One of the really positive other benefits of these other ways of delivering prep medications is that they could be combined so they could be co delivered with prep alongside other medications. So, and most obviously here, um, prep alongside of contraception. So you can prevent HIV and you can prevent pregnancy with one, um kind of delivery model. But I think one really important thing and something that's particularly emphasized in what we've learned from long acting capita Graffiti prep is that we just really need to not keep inventing new, exciting things. We need to be ensuring that there's equity in terms of access to new drugs. Um, and two new drug delivery models as well as to the existing prep drugs that we have. Um, before we start getting this height about going inventing other things, we need to ensure um kind of global equity in terms of access there. Next. And then finally thinking about prep equity is a really important area of research. You know, we've got prep, we know that it works extremely effective in preventing HIV. But we know that in the UK and in North America, the vast majority of people using prep are cis gender, gay and bisexual men um in urban centers. And that's great. It's fantastic that there's widespread prep peace in those groups, but there's loads of other groups um that need access to prep as well that have a high prevalence of HIV. So it was definitely unmet need for prep in particular in people of Black African heritage in trans and non binary people. Um and people who just don't live in urban cities um and inclusion health groups like people who've experienced homelessness, incarceration, uh vulnerable migrants um in heterosexual identifying men have sex with men, which actually makes up quite a significant proportion of men who have sex with men. And they, we know that they really under access um sexual health services and have much less um kind of health literacy around prep and sexual health. Um So really important research there to increase um and support increased uptake in all of those groups. Um And hopefully something that I'm hoping to contribute with my phd as well. Um So if that there is, oh, and I got one more slide. Uh please uh super. So I'm afraid it's a shameless plug. Um So here at Mortimer market, um one of my colleagues, Manic Coli um runs the gum taster days. So if gum is a specialty that you're interested in, then we've got taste. It is coming up in June. I and we tend to run them about at least twice a year. Um So please do get in touch if you'd like to come and join a taste a day. I think it's a three day option. So you do Monday to Wednesday or when it's Friday. Um come join us and Atwater market and get a taste for gun and see if it's helpful for you. Thank you so much and really welcome any questions. Thanks so much, Erika and yeah, I'll give that one a couple of minutes to pay pop. Any questions in the chap actually question myself. Yeah, your last slide about prep. Yeah. Any interventions that been particularly successful in increasing prep using like more marginalized. Yes. So I think definitely one thing that we need to do is although it's really positive that we're providing prep services so well, here in gum, we know that lots of people don't access gum clinics. So it's about getting prep out of the gum clinic into the wider community. And I think in terms of um making available in GPS, making available in pharmacies in outreach services and it's about meeting people where they're at rather than asking people to come to us. Um So that is, I think really the kind of crux of increasing prep equity, for sure. Okay, thank you. We've got a question from Sam. He says, thank you for a great talk regarding the phd and your phd in prepping homelessness. Um What do you think could be done at the moment before you've done the research to help this group? Yeah. Yeah. So thank Sam. Um So I think my phd is really building on some earlier work that I've done with friends, colleagues here at U C L. So we did a kind of uh baseline survey and found that the prevalence of HIV in people experiencing homelessness in London was 20 times higher than general population, but there was really really, really limited prep use. So in about 1200 people who we surveyed um two people total used perhaps at two out of 1200. So there's obviously massive unmet need there and lows to do. Um I think that there's a few things that could be really useful, although I don't want to preempt my research findings because I've not started yet. But the two things that kind of most have come out of some of the PPI work that I've done are firstly about getting um prepped out of gum clinics. So getting it in find and treat, which is our outreach service, um which goes out to um kind of places where people who are homeless. Um are um including kind of drug dependency units including ST sites getting prep out where people are. Um But also thinking about the real opportunities of long acting preps. So taking a daily tablet and being able to store a daily tablet um can be really challenging. People experiencing homelessness. You might not have anywhere to store it, you might not have your belongings with you at all times. Um You might have other stuff going on in your life. That means actually remember to take a tablet every day is really challenging. Um So I think there's some, I think there's a really positive potential impact there for kind of long acting um pack medications like long acting injectables. Um But there's some challenges too. Thanks. And we just got a follow up question of if you, if there's any specific factors that have led to such an increased HIV prevalence in individuals experiencing going with the Yeah. So I think um I think it's probably a range different factors. So we know that people who, who are um L G B T and in particular trans are more likely to experience homelessness. We know that there's um increase use of people who, there's more people who inject drugs and more needle share ing in people who experience homelessness, um which obviously is a mode of transmission. Um Even really simple things like having a HIV test when we did our survey, more than half of these people have never had an HIV test before in their lives. So, um I think there's unmet need essentially at every stage um of healthcare in terms of the prevention cascade, as well as kind of individual risk factors around things like sex work, um injecting drug use, um as well as things about being really marginalized, about being a really vulnerable migrant on top of being homeless, maybe having experienced sex work or transactional sex. Um uh You know, a kind of a host of vulnerability factors, all kind of collected together, correct? Thanks so much for pleasure. Thank you and hope to see some of you soon down for a taster session or two a market. Thanks.