This presentation from pediatric infectious disease specialist Alexander Newman, MD, MSc, will get primary care providers up to date on oral and injectable pre-exposure prophylaxis for HIV, with reference tables to use in daily practice. Newman clarifies which meds have been shown effective for various populations and discusses how to ensure sensitive care for adolescents. He has answers to patients’ questions on safety, side effects and what happens if a dose is missed, and he lays out the testing protocols that must precede writing a prescription. Bonus: Learn about “on-demand” PrEP as well as DoxyPEP for preventing other STIs.
So this will be an introduction to prep or pre exposure prophylaxis. Um This is a, I, I realize it's actually a very dense presentation. So I might highlight some things on the slides but kind of move through them um without diving into too much depth. Um uh If it's just a little too much information basically, but uh these slides will be available to you all. Um And I'm happy to take any questions uh at the end as well. All right. So, um what we'll do is we'll go over what prep is the different types of prep um and who to provide it for an overview of prep practice. So how to prescribe it, how to monitor it and what to do it in special situations. And then if time allows, um which hopefully it will unless I ramble and I apologize if I do, we'll also talk about a new therapy called Doxy PEP um which is actually kind of spearheaded here in San Francisco um at U CS F. So our first uh foray into prep. So what is it? So, prep stands for pre exposure prophylaxis. It is a prescribed medication for people without HIV to help prevent HIV. And it's supposed to be given before the exposure occurs and that's what makes it different than PEP or post exposure prophylaxis when we give medicine after an incident has occurred to prevent HIV. So this is always before it has occurred and to prevent against HIV. When taken as prescribed, the big take home message here is that it's 99% effective as long as you're adherent to it. Um, especially through HIV, uh, through sexual contact. The numbers aren't as strong for those who use IV drugs. Um, however, they're still pretty remarkable throughout this talk. We'll talk about the three big, uh, pre medications. Um, the first and oldest being oral racine Dinas dysp proxy Fite also also known as FTCTDF for simplicity. I'm gonna call it Truvada, which is the, um, brand name given by Gilead who first made the medication. Um, but now that it's also generic, but for simplicity's sake, we'll call it Truvada from here on out the next medication. Um, often marked as new prep is oral racine, uh, TVI Aleen Amide or FTC TAF that is not generic, also produced by Gilead and goes by the trade name Disco again, given the similarities between the first two medications in their naming. Um, we'll call this one Dyco and the other one Truvada. And then finally on this one I might go back and forth with, I apologize. Um, but we have one injectable medication now and that's injectable cabotegravir um uh abbreviated as cab, also known as Aude from Viv. Um I actually stick to the generic name of this Cabotegravir since it's pretty um uh unique. So the first thing to know about prep is where it works and how it works. So I'm very busy slide. I apologize. But again, just to remind you of the HIV life cycle and where these medications act. So the first thing that happens is binding or attachment uh by fusion of the HIV molecule with the cell membrane, reverse transcription of the uh viral RN A to DNA with its own packaged RN A transcriptase, reverse RN a transcriptase um then integration into the host DNA genome where it then hijacks the cell machinery to produce its own copies, using replication assembly from the cell wall of the host cell and then budding off and where our medications really uh take effect are those two red is there that's reverse transcription. And those two medications um are tenofovir and racine. In those combination pills of Truvada and decoy. Both of them are nucleoside, reverse transcriptase inhibitor. They get incorporated into the um uh DNA molecule that's being made and then terminate trans uh transcription and translation at that or transcription at that point. So it blocks for production of that DNA molecule, preventing anything from being uh integrated. Um Cabotegravir is unique. It's what's known as an integrate strand transfer inhibitor. So it's an ins D is how we often call it. Um And it prevents integration of that DNA, uh that viral DNA genome into the host DNA. So it can't hijack that machinery for reproduction or replication or reproduction. So, there are two different sites um and where they act within the host h or within uh the HIV life cycle. Um Here are all the big formative studies on um on prep and uh the different populations in which they were studied in. Um MS M are men who have sex with men and trans women were grouped together. Um We've had cisgender and heterosexual heterosexual men and women couples. Um and then just cis women alone um kind of going through all of them. They kind of go by year by year in terms of uh you can see increasing efficacy because the study has got a little bit more well refined and, and adherence got a bit better. But the landmark one is called IP Rx. It looked at Truvada versus placebo initially only finding a 44% reduction in HIV infections. However, when they looked at the data, uh on those who had detectable drug levels that uh massively increased to a greater than 90%. So really proved that while the intention to treat was only 44% efficacy. When you actually looked at who took, it was really efficacious, the proud study was next, it was open label, meaning they knew who was taking it um had a relative risk reduction of 86% in HIV acquisition. Eber Gay um looked at what we call on demand dosing, which we'll touch on briefly though. It's not FDA approved. Um Also found a really great reduction in HIV acquisition of 86%. And then the two newest ones discover trial which looked at decoy versus Truvada Truvada then being the gold standard at that point just to make sure that decoy would still work for prep because it was a new formulation. It's a non inferior study, meaning that it was just as efficacious in preventing HIV uh as opposed to the gold standard of Truvada. And then uh the HPTNO 83 doesn't have a fun name. Um but it was Cabotegravir versus Truvada also found to be non inferior for MS M and trans women. Um The studies aren't as um robust, I would say for our uh sero discordant couples are cisgender, men and women. Um Here, sero discordant means that one is HIV positive and one is HIV negative. Uh partners prep was the first one though it did look at um three different medications, Tenofovir alone, Truvada and placebo. In these c discordant couples, they actually had to stop early because in the interim analysis, they found that it was highly efficacious and actually both the inter arms 75% and 67% reduction versus placebo, um which was great. And then uh TDF two again, looked at 10 versus placebo. Also open label at that time, found a 62% reduction. So not as strong. Um but we'll get into what it looked like with drug levels and adherence monitoring. And finally, for this one and not in a relationship um or any sort of C cordon coupling. Um there were many that occurred around the time of ire so kind of happening, happening in tandem. Um that was FEM prep which again looked at Truvada versus placebo. It actually found very low adherence in these studies. And so it ended early because of low efficacy. Um The next study was voice, actually very similar findings. They looked at actually several interventions, Truvada, trufa alone, vaginal gel and placebo. Again, adherence was so low during these studies that they found no efficacy. Um The most recent one though uh was the life study which looked at Cabo versus Truvada again, at this point, since Truvada showed so much efficacy in the um partners prep study, it was kind of rationalized that it would still work so long as adherence was strong. So it's now become the gold standard. Um But Cabotegravir, a new injectable prep um was analyzed against Truvada. Um It was initially designed as a non inferiority study and then actually found to be superior in preventing HIV as opposed to Truvada. So they're both great. Um But Kate seems to be actually even better for our cisgender women. Again, looking at it outside of the intention to treat analysis and seeing who had detectable levels, who did pill counts, who was refilling the medication have good adherence. You do see what should be expected, which is if you take the medication, you have a much um decreased risk of, of HIV incident. So um 75 to 9063 to 78% prevention and then 44 all the way up to 92 that's that IP prex. So which, which was pretty formative in this research. So ultimately, who is prep recommended for right now, we recommend it for anyone, um, adolescent or young adult who is sexually active and at risk for contracting HIV, just broad general statement. The other place I would really recommend considering it is if you have an adolescent or young adult in your practice who brings it up on their own and wants to start taking prep, regardless of whether or not they identify any, um HIV risk practices. So if they say they're not having sex, but I want to be on prep, they dig into it a little bit. But what we found too is that sometimes again, our teens and young adults don't feel comfortable disclosing their, um, sexual practices or drug use with us. And so if they're asking about it, I would highly recommend, um, providing prep for them. Um, within the CDC. They have a beautiful document on, on prep itself. And within that document is a supplement to help assess risk for MS M uh, men who have sex with men and IV drug users specifically. So, it's pretty generic. I pulled it up. Um, just to kind of give you a rundown of what it looks like. Um, uh, but here we see that it's kind of separated by age practices. How many sexual partners? Ironically, they say that less than 18, there's no age risk there though, I would say, um, it's still a higher risk group. It's certainly higher risk than I would say, are 41 to 48 year olds in terms of HIV incidents. But know that that young adult age of 18 to 28 probably 18 to 2223 for, for most of our outpatient providers is the highest risk category. We see the highest incidence of HIV. Um, certainly if you have, um, a lot of male partners, the more partners that you have regardless of condom use, um, increases your risk for contracting HIV. And then the two ones to draw your eye to is the type of sexual practices that our MS M or men who have sex with men are having. So, if they are the receptive anal partner, so we call that a bottom. Um, and they're not using a condom that is the highest risk for contracting HIV. Um, you can still get it if you are the insert of anal partner the top. Um, though, if that's kind of moving your eyes to the bottom here. It's, it's more than one time for the bottom. It's, uh, five or more for the top where it increases the risk. There's a couple of studies that have looked at that either way. If they're not using condoms while having sex, I would say that's a big, um, trigger in my mind to consider prep. And then the other thing to draw your eyes to is how many partners are they having that are HIV positive. And I would addend this to say HIV unknown. So if they don't know their HIV status, I would just consider them positive. And at that point, increase their risk Strat vacation. And finally, it doesn't occur too much in our teens and even some of our young adults. Um, but certainly in the bear area, we've seen a lot of use of methamphetamines. Um, and know that, um, what we call, what the uh community calls chem sex or methamphetamine use greatly increases the risk for HIV contraction as there's kind of riskier health or riskier sex taking practices during those periods. So, ultimately, this is supposed to be used if you have a score greater than 10, which ultimately, if you've had one, if your, if your patient has had one, um, a receptive anal sex partner, um, one time without a condom that already gets in the score of 10 and that should really trigger you to talk about prep, simplifying it. Ultimately, this is where the questions that I would generally ask, um, have they had sex in the last six months? And, um, has it been with anyone with an unknown HIV status with inconsistent condom use or do they have an HIV, positive partner with either an unknown or detectable viral load? The important caveat to this and that I really want to impress around all of our teens, um, and young adults, even those with HIV is that if they get to undetectable, they cannot transmit the virus through. And so we call that undetectable equals unt transmissible or U equals you. So, really, so HIV, positive partner is well controlled, taking their medication wildly adherent and undetectable, that's actually safe for them to, to not use a condom if it's a monogamous monogamous relationship. However, again, it's just about talking it out and seeing if they want a backup method like prep in that situation. And then finally, if they're having sex and they've had, um, a new gonorrhea chlamydia or syphilis infection the last six months, regardless of whether or not they say they're adherent with their condom usage. That should kind of clue you in to talk about prep any one ST I infection last month, six months really greatly increases the risk of HIV contraction the following year. Um And then a separate risk category again is that they're using injection drugs. Um, that should also kind of make you talk about prep use in terms of how we're doing with prep, prescribing. So, prep uh hit the scene at least for 18 and up, way back in about 2013, 2014. Um, this graph looks at how we're doing in terms of targeting our prescriptions for those that qualify for prep. At this point in time, we think about 121.2 million people in the US, um would uh meet high risk uh categories for needing prep. And while we're steadily increasing our pre prescription, it's kind of at a slower rate over the last four years or so, we've seen about at least a 10% increase in these prescriptions. But I think only tho those numbers might only get bigger um as the years go by. Um And we could do a lot more to at least getting above 50 above 60 heck above 80 would be wonderful. And with all things, um there are some disparities and who prep is already provided to. So try to be cognizant of this when you're meeting your young, uh your um youth, uh your young adults and your teenagers. Um What we've seen is that uh there is a gender disparity where cisgender men are offered at more than cisgender women, trans women or trans men. Um, certainly white people are actually prescribed it far more often than nonwhite. Uh people who would qualify for prep at kind of alarmingly high rates. Um The, the last estimate was that 78% of white people who would qualify for prep have been given that prescription versus only 11% of um black or African American um folk or Hispanic or Latino folk. Um And you know, whether that's just due to prescriber knowledge, patient knowledge, just health care, um ability to, to access health care. It's, it's a very complicated interaction but just know when you're meeting your teens and young adults to, to have this in mind. And then finally again, our, our young adults are youth and young adults at the lowest prescription rate of under 20% at this point. Um And while at least under 18 is estimated to be one of the lower incidence population, 18 to 22 is a very high risk population. And you should really be targeting those folks as well when talking about prep. All right. Um So we're gonna move on to prescribing prep. I'm gonna try and give you the lowdown of all the differences so that if you would like to have these conversations with your uh teens and young adults in your clinic that you can be well informed and offer them all the same information to make a great uh uh selection of which prep to choose if there are options for them. So first and foremost, this is kind of a table summary of differences of the three that are available, you know that um the uh men who have sex with men and trans women have the most options and that they can select from any of these three Cisgender women um can choose from Truvada and Aude. Um And then Cisgender men really have only been studied. Truvada has only been studied in that population. So technically, that's the only um FDA approval group or sorry, Cisgender men who have sex with women. Um Truvada is kind of the only technical option for them. However, we can probably bend the rules a little bit um um in terms of the differences. So again, Truvada and Visco are oral options. Um the dosing regimen right now is approved by the FDA is a daily dose and we recommend uh supplying a 90 day supply at each uh visit that you see them for in terms of uh for Truvada, it since it was the first to market, it's actually the first that's now become generic and so cost wise is probably the most affordable with or without insurance or without supplemental insurance. Um The other nice thing is it is the first to market. We have a lot more studies and a lot more safety data profiles. A lot more people have been on it as opposed to the newer ones. So um if if folks are kind of worried about um you know, taking the newest thing because they don't want to be quote unquote experimented on or anything like that, not that they would be um that you can offer them some reassurance that this has now been over a decade in use um in terms of providing exclusions again, it's for everyone. Um However, it only goes down to 35 kg in terms of dosing and then um we'll talk about the side effects later, but we do see an increase in creatinine for those on Truvada. So if they already have um a uh creatinine clearance of less than 60 they should not be provide provided Truvada. As long as it's greater than 60 they can still take it safely. Um for decoy again or you know, take it daily. Um It is only brand named uh made by Gilead. Gilead does offer a copay card um that they can apply for online or over the phone. Unfortunately, those on um government supplemented insurance. So things like Medicare cannot qualify for Gilead though. Medica can pay for um a lot of the medication. It's not all of it though. And unfortunately, I don't know the cost offhand. Um The nice thing about it compared to Truvada, I will say is it is a much smaller pill about a third of the size. So if they are pill phobic, um this one is much easier to swallow. Um And again, exclusions for um prescribing that 35 kg is the big one there. Um It's really not approved for cyst women in the sense that it hasn't been studied in cyst women or trans men. Um And it's not for IV drug users. That's not a group that has been studied in. Um similarly, it has a slight bump in creatinine clearance. Uh It's like, I, sorry, sorry, it's like decrease in creatinine clearance, like increase in blood creatinine. Um But uh it's got a much lower value. So as long as it's greater than 30 you can still provide it for them. Um for both of them, if they've missed uh for both Dyco and Truvada, if you've missed a dose again, it's a 24 hour uh it's in every 24 hour pill. Um So they have within the 12 hours of that missed dose to still take that dose and still resume their daily scheduling. So if they're supposed to take it at 9 p.m. before 9 a.m. they realize they missed yesterday's dose, they can take it again and still resume their daily schedule. If it's after 9 a.m. In this example, they just skip it and go back to the next day's dose and that's ok. Um That will differ greatly for aptitude, which is why I bring it up. So aptitude or Cabotegravir, it's our first injectable. The nice thing about it is that it's given monthly to then bi monthly after you get through the loading dose phase. Um It is not available in generic, it's made by Viv. They also offer a copay card also limited by government insurance though. Um but still should be moderately covered though that also, uh they also needs to have a um in office visit for the injection itself. So there are some charges with the actual administration. The nice thing about it is that it's discreet, there is no daily pill. They don't have to have a pill bottle at home. Um They just have to show up to their appointments. The big problem with this with aptitude is that it is long lasting. So if they miss a dose and there's a very tight window about seven days, 7 to 10 days or so that they sh they should be getting their doses on time. They miss that they need to place an oral prep until their next dosing appointment and then they have to restart the whole loading dose um uh situation over with the every 28 days and then moving to every eight weeks. Um exclusions for that though. It has the most limited amount of side effects, which is really nice about our integrase inhibitors, I will say. Um so the only prescribing exclusion is that um is that weight based one? And I will say there is a weight limit in the sense that once you get above, I believe a remember the BM I is, I think it's above 100 and 50 kg though. Um they have an increased dosing regimen suggestion. All right, side effect profile. Always important to talk about these with your patients before prescribing prep. Um uh the two oral pills do have what we call an initiation or start up effect. Um That just means within the first month, as I always say, is their body is kind of getting used to it. They might experience some changes to their body. But that should decrease with time. Truvada has headache, nausea and upset stomach and about 10% of individuals. Um but again, that uh goes away after the first four weeks or so of of therapy. Um The big one for Truvada is a reversible decrease in creatinine clearance. So, increase in serum creatinine. So it's completely reversible. However, they already have underlying kidney issues and have a creatinine clearance, less than 60 Truvada is not the medication for them. Um We've also found that it has a reversible decrease in bone mineral density not to the point where we see pathologic fractures or breaks. Um And Dexa scans can we are the ones that kind of detect? But we don't recommend Dexa scans or, or screening x rays or anything like that. It's just if you have a uh patient who already has a low vitamin D I put them on a supplement or if they have a history of say rickets or something like or some osteogenesis issue, then again, Truvada might not be for them, but it is completely reversible, which is important to tell folks. Um And there are no metabolic effects that we know of for Truvada though. Disco again, it's kind of cousin in a sense. Um It sort of affected diarrhea, not so much the other effects though, which is nice. It had less of an impact on creatinine clearance still has a mild one, still completely reversible. Again, we have a little bit more wiggle room where as long as their creatinine clearance is above 30 you can provide uh disco there are no musculoskeletal effects that we know of. Um I will say it's often marketed as new or safer prep for that reason. I don't necessarily love that marketing, I'll say because both are quite, quite, quite safe and both are reversible once the medications are stopped. Um disco has the added side effect of weight gain about 2.2 kg on average or about £5 not that significant but important to tell folks about. Um And then we have seen increased triglycerides again, never to the point of needing to stop the medication. Um One thing I will say is that the as you can kind of infer with weight gain and increased triglycerides, we don't actually know if there's any cardiovascular effect long term as these, this is a newer medication still being sussed out but nothing. Um overt has come out from the initial data series and then aptitude or kiter. Um again, love my integrase inhibitors. They're wonderful because they have so many minimal side effects. As you can see here, the only side effect is that you can get injection site reactions. Everything else is very minimal or less than 1% of the time. So just warn them that, um, it's gonna hurt and also to say it out loud because I've had a lot of, um, of my patients ask about injectable medication for their HIV. It is given in the glute, it's in the buttocks. Um, and that's always in the buttocks. That's all we have for them right now. Sometimes in the thigh. I will say those are special circumstances. But, um, it's important to talk about that and make them prepared for that. All right. So you've kind of, uh, gone over now, all the different forms of prep, you've discussed it with your patient. They've chosen it. You're ready to do the first visit and kind of, um, initiate prep therapy with them. It's a busy slide. I apologize. Um, but the first and most important thing to do again, these are individuals who are at risk for requiring H I, so we're providing them prep, which is either two medications or only one medication effective against HIV. Um, as a reminder, I just said this before when we treat HIV, it's three medications. So this is inefficient to treat HIV. If they have it, it is really important to make sure they don't have HIV, before starting prep. It's really most important thing about the first visit. Um, and so you need to assess them for acute retroviral syndrome again, that indicates active HIV. Infection, active replication, high amount of VM or high amount of virus in your blood stream. They'll generally present with flu like symptoms. That wonderful generic catch all that's just fever, achy body, um headache. And then you'll also hopefully find um diffuse adenopathy notches under the neck, under the armpits and inguinal lymph nodes, especially um the first uh site that most HIV infections take place is in the G I traffic and often because it's acquired through anal sex. So, um during that visit, just make sure to do a very extensive lymph node exam. Um not, not just the neck under armpits and the inguinal area as well. If they have those symptoms, send two HIV tests. The reason we do this because we need two positives to confirm an HIV test. So you may as well just send both right off the bat. That's the HIV antigen antibody test, often called fourth gen or fifth Gen HIV testing. Um as well as an RN A PC R or a viral load. Um The reason you don't want to just send at least the HIV antigen antibody is that during the acute thymic phase, those tests can sometimes be falsely negative because of the very short what we call window period where they'll be negative, but the RN A will be positive. Again, send both tests. We need two positives, confirm a diagnosis. Um If you move past that they don't have any of these symptoms, they're feeling great. Um, they don't have HIV or at least they don't have acute retroviral syndrome. Um These are the tests that we recommend sending at the initial visit. Um So for everyone again, they still need an HIV test. If they're on oral therapy, we recommend again just the fourth or fifth gen HIV antigen antibody testing that will often reflex to um a viral load if it's positive. Um but it's, it's still safe to use just the, the moment those kind of window period there. Um because injectable therapy you give it and then it's on board and in them for at least a month. Um This is the one where we really don't wanna miss acute infections. So we do recommend sending an HIV one RN A um for those unin. So it's a little bit of difference between the orals and the injectables in terms of what kind of HIV test you're sending, everyone should get an ST I screening again, we're putting them on these medications because they're often at risk for acquiring a sexually transmitted infection. Um And so you should make sure to send gonorrhea and chlamydia testing from every orifice. So that does mean talking about where they're having sex, oral sex, anal sex and sort of that sex and then making sure either swab or send urine testing from all those sites. And then we also recommend an R pr um, there's a high coincident rate of HIV acquisition with syphilis or at least syphilis is really coming back guys, honestly in California. So it's really important to, to really do these R pr testings. Um if they are taking oral prep depending on the kind. Uh So for both of them, we wanna assess gratin clearance. So in A B MP or you can just anonymously and isolated creatinine, we do want to send in Hepatitis B and C testing honestly for everyone because that can be transmitted through sex. But importantly for um the oral preps because the uh medications and oral prep are actually effective against Hepatitis B and to a lesser extent Hepatitis C. And if you stop those medications, they can get a flare of either disease. And so knowing what their status is before starting it, um is important or at least sending the test before starting it is important. And you can just send those with the typical serologic testing for hepatitis B and C. Um And then we also recommend a lid profile for those who are taking uh decoy only. So that's an FTC taf because again, it can cause hyperlipidemia if again, you've sent all these tests. Um and you've assessed them and they don't have acute retroviral syndrome. We do recommend sending them with a script so long as you're gonna get an HIV test result back within 48 hours or so where we find the biggest break is that, you know, we see the patient, we do the test testing, we wait a bit and then we call them and say, hey, we put the script through sometimes that script doesn't get picked up. And so having them have it in hand or just walking over to a nearby pharmacy to have it right after the visit. And then just saying, hey, I'm gonna call you with results. You can start it um for oral prep. That's great. Right? So I'm gonna show kind of two back to back slides of what the follow up will look like. Um So for oral prep, um I would say the CDC doesn't always recommend this. I like it for my teens and young adults. Uh because pill adherence is, you know, can sometimes be questionable for our teens and young adults. So, um one month after initiation, I like to just do a little video visit um and just check in with them and see how they're doing with the medication. The other thing I like to ask about is what side effects they're experiencing. Sometimes those will be the initiation effects that we talked about. And so you should reassure them that those should go away as they continue to take the medication. Other times they might be experiencing something different, whether they've got a concomitant virus or something else has happened to them where they're experiencing some symptoms that might not at all be associated with oral prep. It's important to kind of suss that out and um reassure them that it might not be the oral prep. So they don't self discontinue without telling you that. Um, and we'll kind of highlight through all this, but discussing risk reduction at every visit is really helpful and that just means kind of adherence, safer sex practices. Um, you know, discussing with your partner with the HIV status is um all of those things um, every three months after you initiate prep, oral prep, um they should be coming back in for repeat HIV testing as, as mentioned before, we'd like you to prescribe a 90 day supply. So they should be coming back in for a refill as well. Um For uh you know, folks again, assess how they're doing with condom adherence if they've mentioned that they haven't used condoms 100% of the time or even on oral prep, um You should go ahead and repeat ST I testing again through every orifices that they, they've had sex with and then refill the script. Um Yeah, for every six months after you initiated it. Um This is where it's recommended for everyone that they repeat ST I testing, it's not just optional. Um I would just discuss with them to how they're doing with the prep. Do they want to continue on it? Uh And then in this case, if they've had a creatinine clearance for that, that's less calculated to less than 90 for both Dyco and Truvada, we recommend just repeating it at that time just to make sure it's still above 60 or above 30. Um, and that it hasn't been impacted too greatly. Um, and then yearly again, if they've had a normal creatinine clearance, you just repeat it yearly. Um, just to, again, check in on it and then for disco patients repeat triglycerides just make sure they're not rising, um, too much. Um, and they are not getting into the danger zone of being too high. Um And then again, through all this discuss risk reduction, this is the same thing we kind of just talked about just in graphical format in case you like uh just kind of spot on a table of what test to send and where um in this chart just to orient you, MS M against stands for men who have sex with men and TGW is transgender women. Um And then PW ID, uh people who inject drugs um very simple slide uh didn't know how to build it out, but I think this is a really powerful slide personally. Um in looking back at all these studies, there was a really great review that looked at how they assess drug levels as well as their instant rate of HIV and kind of the separated patients and pull them all together from all these different studies to try to come up with a um baseline of how many uh pills you'd have to take a week to read uh impact uh impact HIV incidents and they really did find a nice little stepwise cut off based on how many pills could be, uh, were either reportedly taken or, um, could be sussed out based on drug levels. Again, baseline incidence rate would be 4.2 per 100 persons years, drops to half. They take, uh, less than, or equal to two per week. Um, if they take 2 to 3, which kind of confuses me because they have less than, or equal to two and then they have 2 to 3. So I guess it's around 2.5. Um, it drops down significantly to 0.6. And then as long as you're taking four or more, uh we're really happy about that and they should have an instance, risk of zero. And so I would say too, you know, it's always important to assess adherence with your patients. So long as they're taking four or more pills a week, I not to, I really, again, try to lean in and say, hey, let's see what we can do to, to get that adherence up to 100%. However, it's not that they have to, um, you know, be too worried if they're taking, they've missed a pill here or there once a week or so, um, they're still achieving adequate drug levels to provide protection against HIV. Like, can we shoot for 100% for a little bit under that? I would still applaud them, I think that's still wonderful. Um I'm gonna briefly touch on prep on demand. It is not FDA approved. Um And uh bluntly, I don't think it's great for teens uh because it's not, uh I mean, adherence is already hard and then uh doing an on-demand medication, I think will be even harder. Um But even so just to make you aware in case you get asked about it by your um teens and young adults. So, um first things first is the design for those who are having infrequent sex. So only every once in a while, um where taking a daily medication might be overly burdensome and um not really impact um them because, you know, they're only having sex once or twice a year. Um know that this study population that it was studied in was only adults so greater than 18 years old men who have sex with men. Um So that is really only a population that truly could see any benefit from it, at least as far as we know from our studies. Um It's not FDA approved. Um And it was only studied for Truvada. So disco cannot be used for this and certainly not aptitude. Um And the other big thing too is it's not for those with Hepatitis B as mentioned before, the components of Truvada can um uh treat hepatitis B. And if you're taking it intermittently, you're gonna get flares of Hepatitis B which can lead to liver damage. Um, what it is though is that, um, you've got the Truvada pill between, as long as it's 2 to 24 hours before they're having sex. So they have to plan to have sex, which I think is already hard for teens. Um, they have to take two pills of Truvada then, uh, 24 hours after those two pills and as long as sex occurred in between there they take another pill, just one. And then 48 hours after those two pills were taken, they take another pill and then they can stop so long as they don't have another and they don't have sex again. Um, anytime soon I think again, this is hard just because again, they have to remember these things. It's intermittent dosing, it's on demand. Um, and they have to plan to have sex, which I don't know how often our, our youth and teens are really doing. Um, the other thing to note too. And, and this is why it's not quite yet FDA approved is when they looked at the data for how often those in the study were taking their on demand prep. It really averaged out to 3 to 4 doses per week, which as I showed from the other slide is, is equivalent to taking it nearly every single day. Um So is it really that different in this group that was studied because they clearly had a high amount of sex? It's, it's difficult to say it's approved in other countries though, in Europe and in Australia especially. So, um if other folks are hearing about it, um I would just have a discussion with them and see if it's really right for them. All right, moving on to injectable therapy. Um So this looks a little bit different and it's often just because of how often the injections are given. Um So one month after initiation, they do have to show up because they have to get their second loading dose to maintain adequate drug levels. Um I would assess side effects at that point. Um And then repeat HIV testing as well that said HIV one R or HIV RN A viral load um and discuss risk reduction and then every two months thereafter, they're gonna be coming in from their, for their Cabot your dose. And so at that point, that's when you should be sending HIV testing is a little bit more frequent um than those on oral prep. And that's only because that's when they're coming into your appointments. Um So that's when you should get it uh every four months um after the first or every four months after the initiation of Cabot takers when we should do HST I testing. So, again, that's a little bit more than the three months. That was optional. A little less than the six months. That was uh recommended. Again, it's just because of the frequency of visits and then yearly um, talk about whether or not they want to continue, uh, prep, um, discontinuing this looks a little bit different than the other one. We'll talk about that because of how long the drug stays in the system. Um, but it's really important to have these conversations frequently and make sure it's right for them. Again, this is testing schedule if you like, uh, diagrams and tables better. All right. So the importance of risk reduction as I highlighted in every one of those little boxes. So, um you might be thinking to yourself, you know, if I prescribe prep, um and they're not using condoms, will they use it less? Because they now know that their, you know, their risk of HIV acquisition is, is minimal and the answer is muddy at best. Um The early studies um when prep was kind of new on the scene is that they actually found an increased adherence rate for condoms and a decreased ST I incidence. Um Part of that might be the Macmillan effect. You're being observed, you're in study. Um You know that you're at risk for HIV because you keep getting counseling about it. So that's what led to that increase as prep has become more at least widespread and as communities become more aware of how protective and efficacious it is. Condom use has seemed to decrease and ST I incidence has risen with that particularly among men, men who have sex with men. Um So we find out later studies that, that uh that effect kind of increases, that they still might be at risk for gonorrhea chlamydia and syphilis by no means, am I suggesting that you should not provide them prep because of this risk? There's always a confounding effect to that. Now you're testing them maybe up to every three months for gonorrhea chlamydia and syphilis. So are we just picking up more cases because we're testing more, it's really hard to say. Um But just know and just kind of re um go over with them the importance of condoms still, while using prep, it really should be talked about as a backup method for preventing HIV, not the primary method. Um Though, again, it is 99% effective. All right. So special situations, um really busy sliding and I apologize. And this is just to reiterate though, um that for positive testing, we need at least two tests to confirm an HIV diagnosis. And so, um while they're on oral prep or cate Gravier, um if you get a positive test, so if it's an antigen antibody test for those on oral prep, um we recommend sending off an HIV one RN A assay with that or should reflex to it. Um If they're discordant and only one of them is positive, uh We recommend sending an HIV one RN A essay again. Again, we want, we want two positives here. And so this will be the tiebreaker and So, um, if that second HIV, one RN A is positive at that point, they do have confirmed HIV, if it's negative and they do not have HIV. So regardless of which one is positive in the first incidence, you gotta use the tiebreaker. And if you got two positives, you, you've got, you've got confirmed HIV. If you've got two negatives, you don't, um, if both are positive right off the bat that's confirmed HIV, both are negative and you're HIV, negative. Um So, um certainly give us a call if there's discord results. Um we actually field a lot of these calls and are happy to talk to you about them. Um But this is just kind of a general algorithm that we follow and what to do. This is where it gets a little sticky because breakthroughs are actually exceedingly rare when patients are, are adherent. Um And so for those on oral prep, um if they've got a preliminary positive result and you're waiting for other ones and your question is, what do I do? Do I stop the prep? Do I continue the prep? What do I do? All I will say all of these recommendations are based on quote unquote expert opinion. So someone in the field said this and that's what we're doing now. Um For those that, you know, kind of talk about intermittent dosing, whether they're doing 211 or they say, uh you know, I miss like a handful of pills a week. So I'm only taking it three out of every seven days or so. I it's a complicated answer actually. Um, you can either hold it or continue it while awaiting results. There's no good answer here. Um, and it gets into some complicated uh um testing that we often do um when we suspect resistance, which I can kind of hold towards the end but know that that's not an easy answer. Please call us about that. We'd be happy to talk about it with you and kind of assess it on a case by case basis. If you got no mis dosing though, the recommendation is still to continue prep and then to consider adding on a third medication effectively, at least giving them active HIV therapy at that point. Um, we'll talk about resistance while on prep when acquiring HIV. It's very rare. And so the reason and rational for that is to give them effective HIV therapy if they have now HIV positive. Um, because we're, it's likely not resistant, but they need to be on treatment. But regardless if they have a positive test while on prep, if you want to talk about it, we'd be happy to field those calls. Um, simpler answer for injectable prep is to please stop giving it, um, and to hold on giving them all medications until the results are known. Um, so at least that one has a simple answer which is just, just stop So kind of jumping right now to resistance while on prep. So these are kind of looking at every study that at least um reported that data as well as had data on the resistance profile. So again, that form of study, the IP Rx study, uh well, first and foremost know that resistance is rare uh on those with h with breakthrough HIV infections, except for Koger rare, which we'll get through um for IP Rx. Um, they found that two out of the 48 of those that had break through HIV infections that were while they were on prep. So again, they look back, make sure they had missed a positive and somehow enrolled them on study. Um, but two out of the 48 had a resistance mutation. Um for uh uh N RT is, which is the class of medications that uh Truvada is. Um So that's uh you know, one out of 25 or about 4% 5% resistance rate, which is higher than the baseline rate of 1% within the general population. But, um, it's not so striking um that we've seen it's, it's just slightly increased partners prep had a, had a bit more, it was three out of 21 but they found more um uh different uh resistance uh mutations than just the M 184 I mutation. Uh It's harder to get an estimate that at that point, it's still above uh the general population, the slightly worrisome one I would say, and we're still looking into why this is and what this means. Um But for Cabo Revere, nearly 50%. Um So four out of nine of the breakthrough infections had an integrate strand inhibitor resistance. So that's actually pretty huge. You're, you're talking about 50%. That's wildly bigger than what we see in the general population. I will draw you to the number though only nine breakthroughs. Nine out of um Oh gosh, it was 200 to 300 individuals on Kate Revere. Um So, well, even more than that, actually, I gotta go back on that. Sorry about that. Um But uh an increasingly small number had breakthrough, but those that did breakthrough had a resistance. Um So that's where it's a little bit concerning. Uh we're still looking into it. We still recommend um injectable prep for those that qualify, but the rate was higher than those that broke through while on uh uh the gold standard of Truvada, take all the standards just so, you know, it's about 115. Thank you. Time stamp. Thank you. I appreciate it. I think I only have a few more slides. So. Oh, good. I'm doing pretty good on timing. Um Thank you for that though. All right. Um So stopping prep. Um So it looks a little bit different for oral versus injectable. Um And the first thing I'm gonna draw you to is kind of this graph over here on this prep and HIV resistance. So we not the highest risk of resistance. So, um, this green zone is that they're doing great with their drug, with their medication. They're taking it every day. Um, they're at no risk for infection at no risk for resistance. White here is that they're not taking any drug. They're at high risk for HIV, but no risk for resistance. This kind of, uh, red zone is where they're either intimately taking it or slowly pulling off of it. So they have detectable drug levels, not enough to prevent HIV acquisition, but enough to influence and select out um HIV, resistance mutations. So this is kind of the danger zone zone. We're starting to talk about it or they're having decreased adherence um for oral prep though, uh that drug effect only lasts for about 7 to 10 days. So if they stop it, um whether abruptly or after guidance in talking with, you know, that that's a risky period for them to contract HIV and a higher risk period, um for them to get resistant HIV, because of the lowering drug levels. So it's really important to express them that they need to either be absent or use a condom every single time they're going to have sex. Uh during that time period, I would say you should still talk about condom adherence from then on out with them. Um, but they still haven't changed their risk profile. Um And you should continue to discuss HIV risk at follow up appointments. Um, I would also say too if they're, he be positive and you did start them on uh daily Truvada. Um, and daily or daily Disco V it's important to monitor them for flares. So, um, monitor the liver unsent for a few months after that. Injectable prep is again, it's newer. So we don't have the best data on it quite yet as to how long this tail effect lasts. The estimate are months to years right now, at least six months is the bare minimum of the tail effect. So it really lingers in the system for a while. And as again, that uh drug load decreases, the risk for acquisition of resistant HIV increases. And so if they want to stop injectable prep, and this might be a conversation to have with them at the first meeting is that once they stop, they still have to take an oral prep medication to prevent the acquisition of resistant HIV. Um And so, uh you should start that within two months of the last cab dose if that's when they decide to stop. Um And uh I would say provide it for again up to six months or so and continue to discuss and reinforce bearer methods and abstinence perhaps during that time. Um And then I would say continue to meet with them at minimum every three months to, to test for HIV. So stopping cate is no small feat I will say. Um, but it is possible and it is something that you can discuss with your patient again. All this kind of goes to the wayside too, if they're now in a steady monogamous relationship or have changed their risk taking behaviors where they're no longer at risk. Um, uh, in terms of providing them prep, but it's a kind of case by case we're again happy to discuss those cases with you. Um The important thing to know is why I would still suggest talking about HIV with those that plan to stop. Um It's just this uh lovely uh um study here which found that um that HIV risk is still present and those that decide to stop and not take it anymore. Um As you can see, it's actually higher than those that were linked but not prescribed. Um And certainly is not higher than those that were persistently on prep. So the risk still is present in the general population is a instance risk of four. So it's still maybe a little bit less, maybe because they're linked to health care, but it's still there and kind of uh kind of goes up as opposed to those that were linked but never prescribed it. So um still talk about HIV, still talk about it, still test for it, still reinforce um uh risk modifying practices. All right. So in summary, it's one of our most effective prep is one of our most effective tools to prevent HIV. Infection should be offered to teenagers and young adults, especially those at higher risk for acquiring HIV. And certainly for those that just ask about prep and want to start it, there are disparities that exist. So it's important to kind of internalize those and make sure you're discussing it among all of your patients that will qualify. Um it requires close follow up and careful monitoring, but resistance in the event of breakthrough infection is exceedingly rare. Uh And patients should continue on even after stopping prep if they have not modified their risk taking behaviors. And so you should still continue to talk to them about HIV. You can always put them back on prep or talk about at least about uh risk modifying behaviors. And these are some useful prep resources for everyone. Again, I got most of these actually from the practice guidelines of the CDC. Um Please prep me as a national organization looked at increasing prep. They've got so many great resources, including posters, handouts, um different uh walkthroughs for insurance. Um It's really a great resource. Um And then I edit this at the end. I don't actually think it's on the slides. Um We and infectious diseases actually do not provide prep. The reason for that is a kind of uh uh breaks confidentiality if you're referring someone for it to an infectious diseases practice without an infection. Um And so all of our referrals should go through the Team clinic in Oakland if you'd like to have them seen within the U CS F system. Um I believe adolescent medicine too over uh sorry team Clinic in Oakland or the adolescent medicine um clinic over in uh San Francisco as well. Again, these resources can be used for you to provide them in clinic if you feel comfortable. Um We'd be happy to kind of guide you um as questions arise to if you like to implement them in the in your clinic. Other thing I forgot to highlight has come up before too. Uh as we were talking about injectable prep, uh as you can imagine, it's a lot of heavy lifting when they get the medication to um get appointments for injections to make sure to make sure your patients show up on time and uh within that window. Um It is a kind of a high barrier to entry in terms of practices implementing it. It's one that we have not yet overcome in either the teen clinic or even in our infectious disease clinic. So we do not have injectable HIV medications at either side at this time. But locally in the Bay Area, there are several, several uh youth facing sites that you offer it. And so we're happy to connect you to that if that is what your patient um desires in terms of their HIV prevention practices. Perfect type in the Q and A and then I'm gonna briefly highlight a brand new tool in our arsenal prevent um sexual acquired infections. Uh first. Well, I shouldn't say it's been spearheaded, I would say at U CS F, there have been several studies that occurred before that kind of influenced the studies at U CS F. But it's wonderful and you might be hearing a lot more about it, especially from your young adults who it's approved, approved in. Um And so what this is called is doxy Pep kind of a busy slide. It's Kaplan Meyer estimate over here on the right side. Um But what doxy PEP is, is its post exposure, prophylaxis a little bit different. They're looking at Doxy prep right now, but for now it's Doxy Pep. What it is is it's Doxycycline 200 mg given once 24 hours to 72 hours. Um after having unprotected sex. And what we found is that it is really great at decreasing um acquisition of new sexually treatment infections. And the one it's most effective against is chlamydia. Second most is gonorrhea and then uh syphilis. Uh well, the uh infection rate was so small. They couldn't make an estimate though, theoretically, we think it also prevents syphilis as well. So, another tool um in in prevention um here on the right here is this Kaplan Meyer curve that looked, that was kind of a landmark study. Um They had a prep cohort and people living with HIV cohort and either did standard care, which was again, was not doxy uh doxy pep or given doxy pep. And then the cumulative prob probably the first ST I diagnosis you can see cut down in nearly half, which was really great to see. So, um fast facts for it is that we only have demonstrated efficacy in men who have sex with men or transgender women. I should say cisgender women were included in both in this study. Um But we did not find as high of an efficacy rate, um or a significant one. And so they were dropped out. Um The only population study is 18 plus. So we can't quite recommend it for our teens. I'm, they're looking at that data right now. Um And so hopefully we'll have something to, to offer for our teens. Again, most effective in preventing chlamydia over gonorrhea, up to, you know, 88% reduction in chlamydia, gonorrhea is 55 percent, which isn't, well, it's, it's pretty big, I guess when the alternative is nothing. Um And then again, syphilis, they didn't actually have that many syphilis infections to actually kind of compare the two rates. Um But uh the biological plausibility states that it probably should be able to prevent uh syphilis as well. And so again, what you do to provide oral doxycycline 200 mg, they take it once within 24 to 72 hours after common with sex and that's all they have to do. And that's where it's efficacious. Um, so it's recently CDC endorsed, they've got a task force, um, right now on it to provide, uh, journal recommendations. Actually, I think they dropped, uh, two weeks ago. So I should update these slides. Um, uh, but, uh, just want to introduce the topic to you guys. Hopefully we'll have more information for you in the coming months to year. I'm hopeful that that timeline is, is tight.
