#22 : Injectable PrEP

HEALTHCARE EXPERTS: Ofole Mgbako, MD; Raphael Landovitz, MD | COMMUNITY REVIEWER: Gary Goldman

SHOW NOTES

The PrEP landscape

The first and currently only in version of injectable prep for HIV was approved by the FDA in 2021. it's brand name is Apretude it's generic name is called cabotegravir
Injectable cabotegravir joins two other FDA approved, oral versions of PrEP for HIV

Truvada, the brand name for emtricitabine/tenofovir disoproxil fumarate, is generic and is the first line option for prep in multiple local and National guidelines.
Descovy is the brand name for emtricitabine/tenofovir alafenamide and is the other pill option to take daily for HIV prevention.
To hear more about these two pill options for prep, listen to our prior episode (from season 1!) about the difference between them

Question is injectable PrEP better than the pill option?

TL;DR: just because it is an injectable option does not mean it is safer, and it does not mean it is better. It depends on the healthcare consumers preferences

But wasn’t it called “superior”?

The statistical term “superiority” that came out of some of the initial studies of injectable cabotegravir is just that - a statistical term.
If someone is taking daily prep 7 days a week injectable prep does not provide “superior " prep coverage.

With those caveats, reasons to consider the injectable form:

If someone has safety issues, health contraindications
If someone has trouble remembering to take a daily pill

Question: are there side effects?

Generally speaking injectable cabotegravir is very safe and well tolerated

The main side effect of injectable cabotegravir is something called an injection site reaction.

This means that where the medication was injected - into the gluteus muscles - is often somewhat inflamed and painful for the 24 hours following the injection
We know that in research that looked at patients receiving injectables that many patients will experience this with their first shot, But as time goes on less and less folks will have issues with soreness at the injection site.

What’s the main concern from a medical standpoint?

Because of the long acting nature of the medication, it is very important that someone's HIV status is known before receiving the medication. This can lead to two potential complications. The first is a delayed diagnosis of HIV due to the activity of the medication that on its own is only part of a full treatment regiment.

The second concerning side effect is that someone who has HIV but does not test positive for it receives the medication, and again because it is only part of a full treatment regiment, they develop genetic resistance to the class of medication that cabotegravir is part of
The labwork that we do before someone receives the injection and at the time of each injection is very important as it allows us to determine that someone is in fact HIV negative. and if they are living with HIV, it allows providers to start them on a treatment regimen as soon as possible.

Can we talk about new HIV prevention technologies and HIV inequities? (Always.)

Dr. Mgbako was quick to point out multiple issues that may further Healthcare inequities as injectable prep is rolled out. These included Geographic access as well as insurance access at the top of the list

Both of our clinician guests also pointed out how providers may misunderstand or carry bias about a patient's inability to take a daily pill and how that may reflect on their ability to show up to an appointment every 2 months to receive their injectable prep on time. in short just because someone has trouble taking pills doesn't mean they won't be motivated to make their Healthcare appointments
Injectable prep is the latest but not the last in the HIV prevention technology pipeline. Both experts were excited at possible future technologies that would allow greater access to HIV prevention as well as greater modalities for patients for whom daily medication or a shot every two months is not the best option for them.

TRANSCRIPT

Injectable PrEP

Dr. Landovitz: If somebody is doing well on an oral PrEP regimen, there is nothing that tells you must or are obligated or should switch to the injectable product. If you are fine on oral PrEP – great.!There is no reason to stop taking it. If that works for you, that's awesome. You are going to be highly sustainably, durably, robustly protected against HIV. But – if it's hard for you to remember to take the pills daily, or if you're using it on a, in a pericoital or on demand way, remembering to take it around the time you have sex – then maybe it's worth considering the injectable product.

Richard: Welcome to Queer Health Pod. I'm Richard and my pronouns are he and him and I'm a primary care doctor who's been caring for LGBTQ plus people for more than 20 years and I'm a huge fan of PrEP.

Gaby: I'm Gaby, she, her. I'm a primary care doctor in New York City, and I self identify as a vaccine queen.

Sam: I'm Sam. And I got really used to getting shots at my doctors that weren't exactly vaccines in my mid twenties.

Gaby: And you're listening to Gonorrhea, uh, I mean, Queer Health Pod, Season 3, Episode 4, Injectable Prep.

Let's introduce the star of today's episode, Apertude.

Sam: That is her stage name on her driver's license. She goes by cabotegravir.

Richard: Cabotegravir was the first injectable pre exposure prophylaxis, or PrEP – that is, prevention – for HIV approved by the FDA in 2021. It was approved as part of a multi drug regimen for treatment of HIV. However, Apertude or Cabotegravir, just on its own, has the distinction of being the first medication approved to prevent HIV that's also injectable and long-acting.

Sam: As a flag, there are other HIV prevention medications that are long acting and injectable, but: those are still in the research pipeline and as of this episode being released are not yet ready for prime time.

Gaby: As another flag, this episode's format is a little different than what you might be used to on QHP. We're gonna let our would be community voices rest, which means we're just gonna be featuring two clinical expert voices on this episode.

Sam: To be clear, we're not abandoning our ship mission wise, storytelling is still a core part of our QHP ethos, but injectable PrEP lends itself very well to just hearing about the clinical details from the experts.

Gaby: There's a lot of discussion and counseling that happens around the use of injectable PrEP, and so we wanted to give our clinical experts a little more airtime to share that information with us because we think it's really meaningful.

Richard: But if you disagree and are missing our community voice, let us know. As always, we are whores for feedback.

Sam: Richard, the kink episode's not till later this season, but…

Gaby: Now we know his fetish.

[TRANSITION MUSIC]

Richard: At the top of the episode, you heard from Dr. Ofole Mbgako, a friend of the pod who you may recognize from Season 2 episodes on HIV and racial disparities.

Dr. Mgbako: my pronouns are he, him. I'm an Assistant Professor of Medicine and population health at NYU Grossman School of Medicine, and I'm also the Section Chief of Infectious Disease at Bellevue Hospital.

Sam: And without further ado, here's podcast guest number two!

Dr. Landovitz: I'm Rafey Landovitz. I am a professor of medicine and infectious disease at the UCLA Center for Clinical AIDS Research and Education. I've been here at UCLA for 18 years now. I'm also the interim Division Chief of Infectious Disease here at UCLA. My research interest and focus is on the optimization of the use of HIV antivirals for both HIV treatment and HIV prevention. And I've spent the last about 10 years of my life working on the clinical development and now implementation of long acting injectable cabotegravir for PrEP, which, as you know, is the first FDA-approved long acting injectable PrEP medication that we have in our toolbox.

Sam: These two guests are, as we call in the biz, gets.

Gaby: In the biz.

Sam: Show business, which I have nothing to do with despite being cast in the chorus multiple times in middle school musicals.

Gaby: I swear to God, Sam, if we hear about godspell one more time I’m gonna absolutely lose it –

Richard: Kids, what Sam is trying to say is that we have a lot to learn from these two clinical experts.

Gaby: Okay, fine. I agree

Sam: Yeah, day by day, Gaby, day by day.

Richard: To see thee more clearly.

Gaby: Now you've derailed Richard we're fucked.

Richard: But we're on PrEP.

Sam: I will pause just to say our Jesus came out shirtless playing basketball at the start of Godspell and it was like just a very like proto homoerotic moment for this young Jewish sheep chorus in Godspell. Anyway, Gaby, you were saying,

Gaby: Freud would have so much to say about that.

Richard: And so will we in the Godspell episode.

Gaby: Okay, back to task. Let's do a quick outline of what we're going to learn today. So part one of this episode is going to review what exactly injectable prep is, how it works, and how it fits into the current HIV prevention landscape.

Richard: Part two of the episode will ask the question: so what is the process of getting injectable prep and what should you expect?

Gaby: In part three, we'll talk about this whole injectable PrEP thing from a health equity lens, looking towards the future PrEP technologies that are on the horizon.

Sam: Section four is when you subscribe to Queer Health Podcast on your favorite podcast platform and share it with a friend who you think would benefit from listening.

Richard: Do that now. I mean, you're already on your phone. It's just a few touches.

Gaby: Before we finally get this episode underway, we want to make the point that at the end of the day we are talking about sex and pleasure. And enjoyable sex, we hope, and protection from HIV.

Sam: Right. Pleasure is a part of this conversation, if not central to it. So come at me graduate student thesis about technology, opening avenues to pleasure.

Gaby: (in affected voice) Through an intersectional feminist lens, obviously.

Sam: It's cool you have Judith Butler on your bookshelf, Gaby. We get it. You went to a liberal arts college, but let's instead hear it through the lens of the people we asked to be on this episode.

Dr. Mgbako: And you see how the benefits that this has when it comes to sexual health for patients, when patients feel that they can focus a little bit more on having pleasurable experiences, on protecting themselves with the latest science and not be constantly worried and anxious about not being protected or not doing the right thing.

Richard: So yeah, sex. Without the fear of HIV.

[TRANSITION MUSIC]

Gaby: Before we get nerdy and fully immerse ourselves in the world of injectable PrEP, we thought we should worldbuild a little bit. Namely, we're going to run you through other non injectable PrEP options. This will be a brief, brief recap of oral or pill versions of PrEP. We're going to breeze through this. For more in depth discussion, I recommend dialing back to our second ever episode on this podcast, the PrEPisode.

Richard: So, there's a red pill and a blue pill.

Gaby: Oh, The Matrix, an iconic trans coded movie reference.

Richard: Mmm, Trinity.

Gaby: I know, tall women, tight leather, slicked back hair. I mean (clears throat) yes, the Matrix, and yes, there are two pills.

Sam: What Gaby, uh, didn't quite get to say there. She seemed a little bit distracted. Was that - yes. There are two pill versions of PrEP for HIV. So pill number one is…

Gaby: Brand name, Truvada. Available as generic emtricitabine tenofovir disuproxyl fumarate, a series of words I really never hope to say again. It's FDA approved as PrEP and has been for over 10 years. And it's a first line recommendation for oral PrEP agents. It's approved for use in folks assigned female or male at birth, and also approved for HIV prevention no matter the reason. So that means that you can take this form of PrEP whether your risk is coming from sexual contact or something else like shared needle use.

Sam: Truvada, horoscope Scorpio.

Gaby: You know, you've been mentioning Scorpios a lot this season. I'd like to dig into that offline.

Richard: Truvada's most common side effects are slight queasiness and diarrhea in about 20% or 1 in 5 of the people. It usually gets better within about 6 weeks though. And it's generally very safe, very well tolerated. We won't get into the very small potential for kidney and bone side effects, but listen to our PrEPepisode for that discussion

Sam: And the pill behind curtain number two is –

Gaby: You know, this whole curtain thing is, it's giving Vanna White.

Richard: Vanna White turns letters. The curtain thing is the Price is Right. What are we even doing here?

Gaby: Okay, grandma.

Sam: Doesn't matter, cause I forgot my spray tan and opera gloves. But Gaby, what's the second pill option?

Gaby: brand name is Descovy. Generically, it's got a name that looks almost identical to Truvada. There is one small change in the generic name for one small chemical component, which is the big difference between these two. It's approved for a narrower group than Truvada. It's approved specifically in folks assigned male at birth whose HIV risk comes specifically from sexual contact.

Sam: Horoscope :Gemini

Gaby: You know, that is a loaded choice for that one, but also my wife is a Gemini and the remainder of this podcast team is made of Geminis, though I actually don't. No, you're rising signs I'm realizing…

Sam: Gaby, Gaby, Gaby - get off Co-Star. We're recording an episode.

Richard: Descovy can cause stomach upset like Truvada, and also there's a reasonable possibility of weight gain of up to 5 pounds and some high cholesterol.

Sam: Can I play the horror violins there now?

Gaby: You can. The lesbian horror violins.

Sam: The lesbian horror violin's back because gay men don't want to gain weight.

[LESBIAN HORROR VIOLINS]

Sam: All right, and with that, we're done with the pill versions of PrEP. Again, generic Truvada is first line, and listen to our PrEP episode from season one for a more nuanced conversation about the two options.

[TRANSITION MUSIC[

Gaby: Okay, so we've gone over the two pill options and now we are on to the third option for PrEP, the long acting injectable known, just as a reminder, as cabotegravir or Apertude by its current brand name.

Dr. Landovitz: The way it works is it's a three milliliter, which is a fairly large size injection in the gluteal muscle, which we colloquially call the butt muscle. And the first injection happens, and then four weeks later there's a second injection, and then it's every two months thereafter.

Gaby: When is injectable prep actually a better option than the other PrEP options that we just discussed? The ones that have like years, almost decades of experience.

Dr. Landovitz: That's sort of the million dollar question. In my mind, there are a couple of things that could make injectable PrEP preferred. The first is if somebody has either demonstrated challenges with taking oral medications as prescribed, or they are fearful themselves that they think it's going to be challenging for them to take an oral medication as prescribed, and they prefer an injection.

Gaby: And I definitely do have patients who have worried about remembering to take a medication every day. So sometimes these folks choose to take PrEP 211 or PrEP On Demand precisely because of this. But we know that PrEP On Demand provides less protection against HIV compared to if you take the pill every day. And so it's actually really nice to have another highly, highly effective option for people who can't take a pill every day.

Dr. Landovitz: We want something that fits into people's lives, that, that they think is going to be doable for them. Because something that's doable is empowering. Something that feels like it's going to be hard or burdensome or complicated probably is not going to be successful. So what somebody prefers, I think, is something that we don't think about often enough and giving people choices that they can understand has to be at the center of a successful HIV prevention portfolio and national effort, in my opinion.

Sam: For those who love the fine print or who social media ad algorithm has figured out that they're gay, then you may have heard the term superiority studied bandied about in some of the advertising.

Richard: This term refers to a scientific study that answers the very specific question: is the new drug better than the current drug? And this is about both efficacy and side effects and safety profiles.

Dr. Landovitz: The studies that, led to regulatory approvals show is in fact “superiority”. But that's a statistical term. And I think a lot of people misinterpret what they mean. Because if somebody is doing well on an oral PrEP regimen – there is nothing that tells you must or are obligated or should switch to the injectable product. If you are fine on oral PrEP, great. There is no reason to stop taking it. If that works for you, that's awesome. You are going to be highly sustainably, durably, robustly protected against HIV. But if it's hard for you to remember to take the pills daily, or if you're using it on a, in a pericoital or on demand way, remembering to take it around the time you have sex, then maybe it's worth considering the injectable product. It's a misinterpretation of what the statistical term superiority means to say, “if it's superior, shouldn't everyone be on it?” No, that is not the conclusion.

Sam: So here are the term superiority means both what it sounds like and what it doesn't sound like. If you are taking daily PrEP and not forgetting any doses, the injectable version is not likely to be superior. For folks who forget a few pills a week of their daily prep, then the injectable is likely to provide more robust protection in preventing HIV.

Dr. Landovitz: Is it safer? I would say safer in what way? Every medication has its own side effect profile, right? And you're treating one thing for another. Tenofovir-based PrEP has its own potential side effects, right? And cabotegravir has its own set of things to worry about, mostly injection site reactions. And in my experience, most people get some tenderness, pain, swelling, redness at the injection site that lasts two or three days, and it's not that bad. There are some people who say, "I don't know why you made such a big deal out of this, I felt nothing." And then there are some people who say, "That was the most horrible thing that I've ever experienced and you are never giving that to me again." Again, everything is about risks and benefits.

Richard: Outside of having a sore ass for a few days, one of the big medical risks of injectable lung acting cabotegravir is the risk of getting with the medication in your system, but not at its fully effective dose.

Sam: Acquiring HIV with injectable cabotegravir in your body has two potential complicated outcomes. The first of which is that if someone gets HIV while there's long-acting cabotegravir, there's a risk that none of the drugs in the class that cabotegravir's in will work for the treatment of HIV.

Dr. Landovitz: None of these prep agents are a hundred percent. So it's something to keep in mind. It's still an incredibly rare event when it fails. I don't know that should be the driving force in people's decisions, but I think informed is empowered. So everybody understanding all of the considerations is important. Some people don't want to know that level of detail. Some people want all the facts. So I think it's important just for providers to have in mind and for patients who want to make a fully informed decision should also keep in mind.

Gaby: We'll come back to this risk of genetic resistance to the medication in injectable PrEP, but let's talk a little more about how injectable PrEP works from like a logistic standpoint.

Sam: So the injectable version comes in what's called a depo solution. It's an oily liquid that then slowly releases the drug into the bloodstream over time. That's how it lasts a long time. After the first injection, blood work is done on the same day that someone gets their subsequent or second, third, fourth injections.

Richard: it's super important for us to make sure that someone does not already have HIV in their system when they get their first injection. So they get tested for HIV right before their first injection and then immediately before each subsequent injection.

Gaby: And the whole rigmarole around this is because of the medical concern that PrEP is only part of an HIV treatment regimen. Partial treatment regimens are good enough on their own for prevention, but are not good enough for treatment. So if someone has HIV, having a partial treatment injected into them can lead to complications like genetic resistance and uncontrolled viral loads, meaning the virus is running rampant in your body.

Sam: Complications like being into horoscopes and you not living in Bushwick or LA, that's a bad thing. Like what's the tarot card for HIV resistance?

Gaby: There was a lot of discussion about this behind the scenes, and we ultimately settled on Wheel of Fortune, reversed.

Sam: And if that makes no sense to you, it makes no sense to me. But, Gaby, what were you going to explain?

Gaby: Cabotegravir, the drug used for injectable prep, also comes as a pill. There is an option of this thing called a lead in, which means taking the pill for a few weeks before starting the injection, which Dr. Landovitz explains here.

Dr. Landovitz: You can start it with a month long daily pill lead in just to make sure that somebody tolerates the specific medication that's in the injectable PrEP regimen, and that's a short acting version of it, so if there's an allergy or a side effect, you can stop it and it washes out of the body quickly. I very infrequently use the oral lead in. I only use it if somebody says to me, "Look, I've got a lot of allergies. I'm really worried. You're going to give me this long-acting medication. You can't take it away once you give it to me as a shot…let me try it as a pill for a couple of weeks first, just so I have the confidence that I'm not going to be allergic to it." And then it's reasonable.

Gaby: So for what it's worth, allergies to Apretude are very rare. That’s one reason, but not the only one, to avoid the lead in or the pill starter schedule.

Sam: Dr. Landovitz had other practical reasons that he recommends against the pill lead-in.

Dr. Landovitz: I think it's actually a liability. And the reason I think that is if you have somebody sitting in front of you who says, "Look, I don't do well with pills, that's why I want the shot." Or "Look, I prefer shots because I forget pills” or “There's something I don't like about pills.” And then you say to them, “Great, I hear you. Take a pill for a month." That's probably not going to go well. And with people are not taking the pill during that lead in period with fidelity. then they become at risk for, acquiring HIV if they're exposed during that period. So, unless somebody really is concerned about allergy and they enunciate that to me, or I see something in their history that suggests that they've got lots of intolerances and they don't tolerate lots of things, I generally don't use it.

Gaby: Common question at this juncture, this juncture being putting two months of medication into your butt muscle. Which is, why there?

Dr. Landovitz: This particular medication, because it is a fairly large volume of medication that has to be injected, three milliliters, it causes the least pain when it's put in the largest muscle. The butt muscle is our largest muscle in the body. There have been some studies looking at this particular medication when used as part of an HIV treatment regimen – so with another injectable medicine going in the thigh. And interestingly, although it looked like it worked okay in that context, people didn't like it. It caused a lot more pain and they preferred getting it in their butt muscle. As long as we have something that's that volume, it's probably gonna be least painful if given in the butt muscle.

Richard: All right, so the shot is a little painful, but so are many of the other shots that people routinely get.

Gaby: Yeah, like, the tetanus vaccine does make my arm sore for a couple of days and if anyone's received a shot of ceftriaxone or penicillin then you know that feeling, too.

Richard: There are also lots of folks who give themselves injections of testosterone or other anabolic steroids who know exactly what this feels like.

Sam: And so while the pain might sound a little bit scarier than it is, this pain or soreness – that you may hear referred to as an injection site reaction – does get better after the first few shots.

Richard: Meaning, the shot gets less painful after the repeated administration.

Sam: Specifically, this was very well documented in one of the studies that was done for long acting cabotegravir as HIV prevention. 86% of folks, when they got their first shot, had this soreness that was enough for them to tell the study about it, which was down to 72% by the second one. And if you look at folks three years in, only 18%, or a little less than 1 in 5, were still having those painful reactions. The same study pointed out that only one person stopped taking the injectable medication because of these reactions.

Gaby: Another question which you may have is, why does the injection have to be done in a clinic and by a licensed provider? And you might be asking that question because you know that there are other medications, like for example, testosterone, that can be injected at home.

Sam: So for now, cabotegravir as PrEP has not been studied as a self administered medication, though that is in the pipeline.

Dr. Mgbako: There are a lot of emerging studies around this, trying to look at this as a potential force moving forward. There have been studies looking at whether this is an option that patients find acceptable and feasible, and largely the studies so far have said yes – getting the injection in sites outside of the clinic makes sense for them. And there are new ongoing studies exploring it in non- traditional settings like the home. So, as you can imagine, that requires setting up a completely new infrastructure to make sure that this is done safely.

Richard: So, it needs to be injected in the clinic, and after the first two shots.

Gaby: Which, again, are one month apart, then every subsequent shot is two months apart.

Dr. Mgbako: this does mean coming into clinic more frequently than if you were taking oral prep. A lot of people already think that's, It's a burden coming in every three to four months to get your oral prep and picking up the prescription from the pharmacy, et cetera. Because it's only nurse administered and can only be done in clinic at this time and it's an every two month medication, really I try to make sure folks who travel a lot, who are seeing a lot of kind of structural barriers, understand the implications of it.

Gaby: So because of these kinds of structural barriers, all of these visits, we did ask Dr. Landovitz if this is something that folks might just use for a shorter duration.

Sam: Yeah, like asking for a friend, like that summer trip just before you go to Berlin or Fire Island or Provincetown or Mykonos or Puerto Vallarta…yeah, yeah, yeah, just for a friend…

Richard: Is it, isn't that your travel itinerary, Sam?

Sam (affronted): Get out of my Google calendar.

Gaby: So anyway, you're covered for your gaycation and then you come home and no more shots, you're off PrEP, or you go on to the oral one

Dr. Landovitz: I have to admit that nobody's ever asked me that before. It's not something I've actually given a lot of thought to my first answer is just because it's so much effort to get the injectable medication. I would think that it's probably worth your while to stick with it for a little bit if you've gone through all the headache of getting it.That being said, there's nothing magical about it, right? If you get one injection and you say, “I hate this,” there's nothing that stops you from going back to oral PrEP. So there's honestly no reason why there has to be any sort of timeframe that you would aim for doing it. If you want to try it, cause you think it might be better for you for a period of time, for a year, for a couple of years – I would not use that as a deciding factor, to be honest.

Sam: But all this begs – just like me in my early twenties – the question, what happens after you stop the Apretude?

Richard: We recommend preventing HIV in other ways if there's still a risk of getting HIV. So here, use these condoms… (snare drum) I mean…

Gaby: It’s SO terrible.

Richard: When was the last time you saw one of these? They're like antiques, but yes, they do work if they're not expired and they're still an option.

Gaby: Okay, what this ham fisted joke is getting at is that on the tail end of injectable PrEP, we do recommend that you use something to prevent HIV. That can be the pill version of PrEP, or it can be condoms. And it's not just because we don't want people to get HIV, but we particularly don't want people to get HIV with a little bit of cabotegravir still in their system, since it can lead to the resistance that we talked about earlier. Anyway, to prevent any more of Sam's cheesy sound effects, let's move on to our recap of the section.

Sam: Rude.

[TRANSITION MUSIC STARTS]

Sam: Injectable prep is an option for folks who have exposure to HIV and want to prevent the risk of getting HIV. As prevention, it's been FDA approved since 2021 and folks assigned both male and female at birth.

Richard: Before the first dose, folks need to have an HIV test on file to confirm that they are actually HIV negative, just like with oral prep. And then the first two shots are a month apart, and then every two months in the clinic afterwards.

Gaby: And it's safe. Don't let the statistical terms confuse you. Injectable prep is superior only if it's superior for the patient in terms of their ability to take it without interruption.

[TRANSITION MUSIC ENDS]

Gaby: Now that we know how injectable PrEP works and the process of coming to clinic to get the injection and the labs every two months, we want to dive a little deeper into some of the medical risks.

Dr. Mgbako: So if someone is exposed to HIV, acquires HIV, and let's say they're two months out from their last injection, and they don't have the levels. of the medication in their body to protect them from HIV, but it's still on board. That puts someone at risk for being on essentially one medication for HIV for a period of time until you diagnose it in the clinical setting. And that could put someone at risk for resistance.

Richard: Because, uh, science and acronyms, this is called LEVI, like the jeans!

Gaby: For the curious folks at home, LEVI stands for Long Acting Early Viral Inhibition.

Richard: And is considered one of the main medical risks of injectable long acting PrEP.

Dr. Mgbako: And really, I think the concern is that with long-acting cabotegravir, that people developed HIV infection while on injectable cabotegravir. That they had delays in HIV diagnosis, and that there could be emergence of integrase inhibitor resistance, right, which is the class that Cabotegravir belongs to, because of how the science works with half life and how long the medication stays in the body, and then the partial treatment of the virus in the body, and the not allowing it to be detected – like, really early enough so that you start a full antiretroviral therapy and treatment to really make sure that someone is virally suppressed and their virus is controlled and everything.

Sam: In this same study, it was extremely rare. We're talking about in the 0.1% category, that someone who was on time for the injections actually got what we call breakthrough new HIV infection.

Dr. Mgbako: And I think just making sure that our patients are aware that is a thing, that that exists and we're working through it, I think is just another part of the effort to build trust with our patients in these conversations. I think the worst thing is If that's just not part of the conversation at all and patients hear it from a friend or hear it from another source or they just don't know about it, period. So I think it's important that even though it's rare, that it's something that's part of our counseling.

Richard: You might be wondering, "What happens if someone is on capotegravir with active HIV in their system?" Well, we alluded to this earlier with our conversation about partial treatments, but in essence, resistance can develop.

Gaby: And Dr. Landovitz talked about how this was a risk during the cabotagravir tail, or this period that comes two months after the last shot and beyond…when the medication is present in the blood, but not at full steam potency.

Dr. Landovitz: In terms of what the risks are: at least in the cis men and trans women, we know with pretty good precision at this point that if somebody acquires HIV within six months of their last injection that is the period where you're most likely to get integrase-resistant virus if you acquire HIV. After six months, we have not seen resistance develop. If it's more than six months for the cis men and the trans women that have been in the studies, you don't get resistance. So that becomes a non-issue six months after your last injection. For cis women, we know a lot less about it. And that's because there have been a lot fewer infections found in cis women in the cabotegravir trials to date. So we just don't know. I suspect that six month number may be a little bit longer just because of the way the drug behaves in people assigned female at birth.

Sam: So, two big points. One, the risk of a delayed detection of HIV, and two, limiting HIV treatment options due to genetic resistance. Both of those exist with long acting PrEP. They exist because the medication can be in the body at a dose that's too low to prevent HIV, but enough to affect the HIV virus.

Gaby: And because of Cabotegravir's long acting nature, if someone stops the injectable medication, we would want them to make sure they know that there is a higher risk of complications if they get HIV in those first few months after their last injection.

Richard: Which is all to say that if those risks, however small, are intolerable to someone, they should know that before they get the medication, especially if condoms or oral PrEP or heaven forbid abstinence, are absolutely out of the question for them as options.

Gaby: Oh my god, did you really just say abstinence?

Richard: I know, it's the A word, we almost never say it on this podcast, but like, if you're gonna be at risk for HIV and you don't want resistance, abstinence is an option.

Gaby: Alright, and because abstinence is an option but hard, let's just say someone gets HIV while on injectable PrEP and develops resistance to the medication class that's in injectable PrEP. What does it actually mean going forward in terms of the HIV treatments available to them?

Richard: Long story short, we recommend that if someone gets HIV, they take a resistance test. This is a blood test that will help us understand the specifics of the type of virus that they have. But both of our experts felt that many of the once daily pill options could still work and that HIV could certainly still be a well controlled chronic illness.

[TRANSITION MUSIC]

Gaby: Before we wrap up for the day, some thoughts on how injectable PrEP fits into the bigger picture of HIV prevention and equity.

Richard: As we mentioned earlier, injectable PrEP is a great PrEP option for those who feel they can't take daily oral PrEP consistently. Unfortunately, that leads to a lot of assumptions about the quote unquote kind of person who needs injectable PrEP.

Gaby: Like, that if someone can't take a pill once a day, they won't show up for their appointments every two months.

Dr. Landovitz: The mistake I think any provider makes is assuming that anybody other than the patient is the best expert on their own lived experience. So I think that's an approach that hopefully medicine is moving more towards is this patient-centered model. I think we still have providers across the spectrum of old school paternalism all the way to the other end of the spectrum of this only patient-centered decision making. I think you have to be, as a provider, a little bit of a chameleon and figure out what a patient in front of you needs and wants from you. I think some people will want you to weigh in with an opinion. I think all patients deserve your best objective assessment if there is a better product for them and why, but ultimately we have to understand why consumers or patients are wanting one thing over another and work with them. I think that providers make decisions for patients that may not be appropriate. They tend to be also assume that there is some monolithic aspects to populations because somebody has been nonadherent with their medication. They won't be able to show up for appointments. That's an example. And I think non adherence to a pill is very different to someone's ability to show up for an appointment, especially where they know they're going to get an injectable medication. Those two things do not equate, and to assume how somebody is going to succeed in attending appointments where an injection is going to be given based on their previous either clinic attendance where they weren't getting an injection or pill taking behavior, I think is a mistake. I think everyone deserves to be able to demonstrate that they can succeed if they think that this is the best product and intervention for them. So that's my approach. And that's a little bit of the context as to where the concern’s from. I think there's always a balance in the approach. And the more you listen to what someone is telling you they want, and you can respond with objective facts, and then make an informed decision together is my preferred approach.

Gaby: The big takeaway here is that this whole non adherent label is damaging and paternalistic.

Sam: She wouldn't be our lesbian if she didn't call out the patriarchy at least once an episode.

Gaby: All in the name of HIV prevention, babe.

Richard: Nevertheless, we hope that folks don't meet resistance or skepticism from their clinicians when they ask to be put on an injectable HIV prevention medicine.

Gaby: All of this is assuming that someone can actually get injectable PrEP near them in the first place.

Dr. Mgbako: Because this is where geographic inequities come into play, right? The idea that there are folks who just don't have access to HIV prevention services, period. And then when they do have access to those services, really the gatekeepers, right, keeping them away from these kind of like amazing scientific options that they have. And so I think about that a lot. It's really tough. And in certain parts of the country, there are these kinds of just deserts where folks don't really have a lot of options. But I think luckily there's a lot of efforts that I know of where it's the really focused on expanding access.

Gaby: One of those technologies that could expand access is an even longer acting version of injectable PrEP.

Sam: Dr. Landovitz noted that there is an every six month injectable medication that's moving through the research pipeline with promising data.

Gaby: Once approved, that medication is going to take a few years to get into clinics, but meanwhile there are other options in the pipeline.

Richard: A long acting pill version of the same medication as the current injectable cabotegravir is also in the works, so that would be one pill once a month.

Sam: While those continue to get studied, both our experts were clear that we cannot make health inequities worse while we wait for potentially better and more accessible HIV prevention technologies.

Richard: Absolutely, given the inequities that exist by race and gender, we need to offer people the tools we have now because any prevention option is better than not having one while you wait for a better one to come along. You can decide what's right for you from the current options and not wait for the future ones.

Dr. Mgbako: There's absolutely a role for self advocacy, and there's absolutely a role for community engagement in a way of, I think we see this a lot with the queer community, that we really support each other, particularly in, at these times when, not only in times of distress, the mpux outbreak, but in times where we need to have greater access to new medications and new therapies. And so really tapping into these networks and really educating oneself and coming in together. With those questions, I think is really important and really advances the conversation. I always think of the prep care cascade, and there's a study that really shows going from first awareness to being offered prep by a provider and to prep use when you look at that cascade, it gets. low, it gets lesser at each juncture. And then we think about the racial disparities along that cascade, they become more and more stark as you go across, right? And so there's really no excuse for black patients to be offered PrEP at a much less rate than white patients. There's just no excuse for that.

But we know that those barriers exist. We know that structural racism exists. And so there is certainly a role for someone to advocate for themselves, to ask those questions. And if this is an option that they want to explore, to be persistent in bringing it up. Certainly there are patients who I think folks will be hesitant about starting it.

But I think at the end of the day, it has to be a shared decision. And if a patient really wants to move forward, I think it's the responsibility of the provider to really support them in that process. And then if it turns out that this isn't the option for them, then that's okay. But I think that there's a higher risk in starting injectable prep and not being supported on that kind of HIV prevention journey than, yes, there might be a lot of challenges, but then being supported by a provider and a clinic and a whole kind of network of individuals just trying to figure it out as well. Figure out how to stay safe and live a pleasurable life and a healthy life. We're all trying to do the same thing.

Richard: Speaking as a Gemini, the future is bright.

Gaby: Speaking as a Cancer, I'd like to go home and make myself dinner, please.

Sam: Speaking as someone who has not found an astrological self insight in this era of morally unmoored late capitalism…let's get into a recap so that all of our astrological needs are met.

First off, oral prep has been around for over a decade. It is safe, generic, and is the first line choice.
Injectable prep or Apretude is the newest agent on the scene and is as effective as oral or pill prep when the pill version is taken daily.
If you're interested in injectable PrEP, you can expect some soreness where the injection goes and going to clinic every two months after the first two doses for injections.
The risks of injectable PrEP are most commonly: that it hurts (known as injection site reactions) and way, way, way, way less commonly, but more medically concerning, is the risk of developing HIV that is resistant to certain treatment medications.

Gaby: As someone with a Virgo rising…this really hit the spot.

Sam: That’s, uh, groovy Gaby.. Why don't you put your crystals and singing bowl away? Maybe it's Richard singing bowl. I don't know.

Richard: It’s mine.

Sam: But let's get back to Dr. Mgbako with some final thoughts.

Dr. Mgbako: I do really believe in this moment of injectable PrEP being rolled out as an opportunity for us to address social determinants and structural determinants of health, for us to think about structural racism and how it's been embedded in the PrEP cascade, and which is really evident in our PrEP outcomes where we see differences by race, and really use this as an opportunity to try to think innovatively and imaginatively to empower people to address these entrenched structures that keep our patients from taking full advantage of these scientific advancements. I think my hope is, even though that this is really new, that in the next few years we'll be having a lot of kind of innovative strategies around that. So that we can truly think about closing some of these gaps and addressing some of these disparities that have continued to emerge over the last few decades.

[QHP THEME MUSIC STARTS]

Richard: QHP is a power sharing project that puts community stories in conversation with healthcare expertise to expand autonomy for sexual and gender minority folks.

Sam: Thank you to our healthcare experts, Dr. Raphael Landovitz and Dr. Ofole Mgbako. We would also like to thank our community reviewer, Gary Goldman.

Gaby: For links and transcripts to this episode, check out our website, www. queerhealthpod. com.

Richard: And please help others find this information by leaving a review or subscribing on Spotify or Apple Podcasts. Not just stars, but add some text.

Gaby: We are on the social media apps. Our handle on all of them is @QueerHealthPod, so reach out to us if you want to chat.

Sam: And thank you to Lonnie Ginsberg, who composed our theme music and to the Josiah Macy Jr. Foundation, who paid for some of the tech we use to produce these episodes and our silly sound effects.

[QHP THEME MUSIC ENDS]

Richard: Opinions in this podcast are our own and do not represent the opinions of any of our affiliated institutions. Even though we're doctors, don't use this podcast itself as medical advice. Instead, consult with your own healthcare provider.

Gaby (very nasal French accent): Life is pain. Anyway.

Richard: Wow, that got really dark! Life is pain. Thank you, Marlena Dietrich.

Gaby (attempt at a ?husky voice): That's what I'm here for darling. I'm taking a drag off my cigarette and I'll be right back.

#22 : Injectable PrEP

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