Why Switch a Suppressive ART Regimen Podcast: Insights From the NCCC

This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.

Dr. Cristina Gruta (National Clinician Consultation Center): Great. My name is Cristina Gruta, and I'm going to start off the session today by reviewing this process of shared decision‑making.

Practical Strategies for Proactive Switch

So, in situations where the goal of suppressed viral load has been achieved, and there's nothing inherently wrong with somebody's antiretroviral regimen - so nothing technically wrong because they're suppressed on it - shared decision‑making is this platform for information exchange between the patient and provider. It's a space allowing the patient to articulate their goals of care or their goals in their antiretroviral regimen. And provides a space for the provider to make the patient aware of all options, the newer options that may have come since their last regimen was prescribed, and present the options in an evidence‑based way. And when the evidence is clear, you know, obviously the provider, it's incumbent upon them to, you know, let the patient know, especially if there's a clinical reason to make the switch to make the switch. But when the evidence is not black and white that the switch should be made, in many ways, presenting them with options allows the patient to see if the newer regimens will improve their goals that they are trying to achieve with their own health.

This may be a discussion on their current pill burden, the number of tablets or doses they're taking per day. This may also include the realization that they may be having potential drug‑drug interactions with their current regimen because of new prescriptions that are being prescribed by other providers. And so, sometimes patients aren't aware that these could be potential reasons for making a switch.

The next thing to do is to identify their readiness for change. So, be prepared for discussions in situations where people really feel like the regimen that they have that they're on now is perfectly suited for them, and they don't want to rock the boat. But we know as providers that the information changes along the way. And so, as an example, we, for many, many, many years, we used to use an efavirenz‑based regimen as sort of a first‑line regimen.

And I can remember in my own practice where many, many patients were really, really attached to that particular regimen specifically because it was the first single‑tablet formulation where all of their medications were in that one tablet. But as time went on, there were - the evidence accumulated that there were longer‑term toxicities with that particular regimen, and we needed to make sure that the patient was aware of that.

And this whole identification of readiness for change, it won't necessarily happen in one visit. It may require a series of conversations with the patient. But in the end, it's still their bodies, right? And it is incumbent upon us as the providers, to make sure that we are informing the patients of the latest evidence of the newest medications and options that they have access to.

And then, together with their wishes, with their goals, and together with the information that we are providing to them about the newest data, you can collaboratively determine whether a switch to another regimen may be more beneficial for the patient.

Questions to Ask Patients About Their ART Regimen

Next, I wanted to review some conversation starters with the patient. So, let's, you know, many times it's actually the patient that comes up to you and says, "Hey, Dr. so‑and‑so," or "Hey, Nurse Practitioner so‑and‑so, I heard this from a friend," or "I saw this on social media," or "I saw this on TV. What do you think about this?" But sometimes they're the conversation doesn't start with the patient. Sometimes people are so tunnel‑visioned or maybe are so wrapped up in the other issues in their lives that the HIV regimen that they're taking is not something that they're thinking about or they don't necessarily think a change is necessary. As I mentioned earlier don't rock the boat if, you are suppressed. But it's also sometimes good to check in and ask patients how satisfied they are with their current antiretroviral regimen. Is it still working for them? Is there something that - about it that might be bothering them but they've just kind of keeping to themselves because they think that, you know, I've had HIV for so many years, I've had to contend with so many problems with my HIV medications that I'm just going to keep this to myself because I know this is as good as it gets?

But oftentimes that's not the case. Oftentimes, in science and medicine, we are trying to improve patient quality with our new innovations, and so we want to make sure that patients are aware of that. And so, we can bring it up to you, to the patient. For instance, is this twice‑a‑day regimen with six different pills still working out for you? For instance, if somebody is taking only once‑a‑day medications for their other conditions, wouldn't it be better? Wouldn’t it be nice if we can convert them or switch them to a regimen that is also once a day, so that they don't have to remember another time of day to take medications? So, that's another way to of dive into is this regimen still working for you?

And then the other question to ask is: are you having any challenges taking your medications? You know, as people get older, they're going to develop new disease states, and they're going to have more medications prescribed. And sometimes the current regimen may not be working from a drug‑drug interaction perspective. Or, as another example, if it's a twice‑a‑day regimen Is that second dose being missed now because they are going to bed earlier, or they fall asleep before they take that second dose?

And lastly, maybe, you know, they haven't thought about this, or maybe this is a good time to elicit if there's anything they wish were different about their current antiretroviral regimen. You know, we always talk about consolidation. Is there a way of giving this regimen in less number of tablets? Sometimes people begin, are on a regimen that was begun during the days before more co‑formulations were available on the market, and they just think that's the way it's supposed to be. As a prime example, people are aware of the protease inhibitor, darunavir.

As we know, darunavir is always boosted with another agent, either ritonavir or it's co‑formulated with a pharmacoenhancer called cobicistat. But the cobicistat coformulation of darunavir did not come into the market from the beginning of the darunavir approval. Darunavir was originally just boosted with ritonavir. But it's a separate pill, and it's conceivable that patients may still be on darunavir/ritonavir. And wouldn't it be great if we could decrease their pill burden by giving them the co‑formulation with a cobicistat‑boosted regimen?

So, these are just a few examples of conversation starters. So, in situations where we want to talk about or potentially introduce to the patient newer options that have come into the market. And so long as there's no clinical contraindication to switching patients over to these newer combinations or newer options, then these conversations - proactive conversations - with the patients - are imperative to have on a regular basis.

And at this point, I'm going to turn over to my colleague, Dr. Moring‑Parris, who is going to discuss the clinical considerations in making switches when patients have suppressed viral loads.

Ask the Experts: Q&A

Approaches to ART Switch

Dr. Daniel Moring‑Parris (Contra Costa Health): Thank you, Dr. Gruta.

ART Switching: Things to Keep in Mind

All right. Now, when you have had all those discussions with the patient, ideally gotten buy‑in to make a change, before you start talking about specifics, it is really important to do a careful review and consider some specifics before listing out some alternatives for the patient.

So, number one, you want to do a really careful review of the patient's ART history and all of their previous genotype results, and get a clear idea of whether the patient has had any previous virologic failures. For some patients, this is very clear. You know, maybe they've been in the same system - for most of their life living with HIV. And you have a nice list of all their genotypes. You have a clear list of all their medicines. There are a lot of patients, though, who maybe they lived in another state or another country for the first couple of decades of their HIV life. And when they come to you, you don't have anything, and they can't remember any of their medicines. So, sometimes it can be helpful to show them a medication chart, list out meds. But it is really important to do everything you can in terms of records requests, patient interview, and take time to get a clear sense - of what happened in terms of their medication exposure, not only virologic failures, but intolerances and potential allergies.

And then before listing out options, especially as we talk about patients that are getting older with more medications and potential polypharmacy, it's really important to proactively check for drug‑drug interactions. Some of them are minor and easily addressed with a dose modification.

For example, some of our boosted protease inhibitors, like darunavir/cobicistat and statins. Some of them are more significant, especially people taking tuberculosis medications or anti‑seizure or psychiatric medications. A great resource for that is the Liverpool HIV Medicine Interaction Checker that gives very detailed, evidence‑based recommendations. Not just saying that avoid, but, you know, specifically saying what you can do to mitigate some potential interactions.

Another very important aspect to consider, which at times as the provider may be the driving factor in talking about a med change. But sometimes it's just something that you have to consider as you make a med change. So, people's comorbidities can really have major impacts. And again, we will often go outside of guidelines for some of these things, but it's always important to make sure that you're aware of standard practice when making a switch. So, a big one is a patient's hepatitis B status. We have more evidence that lone core antibody may not be a contraindication to tenofovir‑sparing regimens. But certainly, patients who have chronic hepatitis B would likely not be candidates for some of our more modern two‑drug regimens that do not have tenofovir, such as dolutegravir and lamivudine or dolutegravir/rilpivirine. Similar for the injectable cabotegravir/rilpivirine.

Pregnancy is an important consideration. Although there are really not any medications that are specifically toxic in pregnancy, there are some that are not recommended. Again, darunavir/cobicistat. And then there are some medicines that just don't have a lot of data. Injectable cabotegravir/rilpivirine and doravirine‑containing agents - are not considered first‑line. But again, you need to know about someone's pregnancy status before the switch.

Two big drivers of switches and important considerations: chronic kidney disease and cardiovascular disease. So, in terms of CKD, you may have patients that are getting close to that creatinine clearance of 30, where you might want to consider switching off of a tenofovir alafenamide regimen. Certainly, if someone has CKD and bone density issues, you're going to be wanting to avoid tenofovir disoproxil. Patients with cardiovascular disease, again, important to be aware of the lipid impacts of protease inhibitors, especially older protease inhibitors, and then also potentially avoid or move away from abacavir‑containing agents. And obviously, there's many, many more niche considerations, but those are probably the big ones.

And then going back to genotyping, as I said, there are many patients who may not have any prior genotypes available. Now that may not be a huge concern for someone, for example, who was diagnosed a few years ago and has never had a virologic failure. You may not need to know the details of their baseline genotype before making a switch, but it can be very impactful if, for example, someone has had HIV since the '90s, they've been on numerous regimens, had exposures to numerous drug classes, and potentially had some virologic failures. In those cases, it really is important to get a sense of their genotype history. And while we don't recommend routine proviral DNA archive genotyping, those patients with long histories with multiple drug exposures and potential virologic failures, those are patients you might consider a proviral DNA archive because it can impact your decisions.

It is very crucial to match the information you get on the DNA - DNA archive with the patient's treatment history. Remember there may be times where it's picking up some previously inactive strains of HIV. And if it doesn't fit their treatment history, you may be able to disregard them. But it is important to consider it when you have an absence of information in a complex patient with a long history of HIV.

And then lastly, when you make a switch, it's very important to increase your monitoring after that switch. The patients we're talking about today are people who are already virally suppressed, and you may have gone out to a every six‑month visit and lab schedule with them, but this is a time to see them a little bit more frequently. We in general recommend a one‑month follow‑up viral load after a switch and consider just increased touches, at least in the first three months after a switch, to make sure they're tolerating it to make sure it's working from a neurological standpoint, and that it's not having any negative impacts on any of their other lab monitoring parameters.

It’s Your Turn!

All right. So, now we can go to some questions. And we love it if people have any complex cases they'd like to ask about, if there are any questions specifically about guidelines, and if we have some cases we can share as well.

And maybe as people are formulating some questions, Cristina and I could talk about some cases. Yeah, Cristina, if you want to start with a case that you have, that'd be great.

Dr. Gruta: Yeah. So, I have this case: a 68‑year‑old man living with HIV. He currently takes bictegravir, emtricitabine, tenofovir alafenamide, and also takes empagliflozin and oral semaglutide, both of which we presume treats diabetes mellitus type 2 and also takes amlodipine for hypertension and atorvastatin. This patient is hepatitis B surface antigen‑negative, hepatitis B surface antibody‑positive, so appears immune from immunization.

He is at goal with his diabetes medications, with an A1C less than seven. His hypertension is at goal, but unfortunately, he has progressively declining glomerular filtration rate. For years he'd been sitting with a creatinine clearance between 40 and 50, but most recently, it's dropped down to between 25 and 29 on the latest lab work despite otherwise being clinically stable.

So, the questions here, Dan, is how would you have a conversation with this patient about, you know, should he make the switch to another regimen and why? Because he's pretty satisfied with it. He's done really well, has tolerated it fine. And it's so easy, or one pill for the entire regimen. And how would you approach this patient?

Dr. Moring‑Parris: Yeah, this is a great example of a common type of patient that we're seeing. And while it's not certainly an emergency to immediately switch as people have, you know, gradually declining creatinine clearance, it's important to identify patients like this and at least open up the conversation. And you can really say that the medicine that they're taking, has served them well and is a great medicine, but as their kidney function has declined, it may increase the chance of toxicity related to that medicine. And the great news is that there are tons of new options that are likely equally effective, but will be a little bit friendlier to their kidneys.

You know, discussions like this are a little harder when we're talking about changing someone to a much more complicated regimen, but luckily, we don't have to do that in this context. You know, we have the co‑formulated dolutegravir/lamivudine that many experts agree can be used with lower creatinine clearances. We have co‑formulated dolutegravir/rilpivirine, which has no creatinine clearance cutoff, which is a great option. This might be an opening to discuss long‑acting injectables. Again, cabotegravir/rilpivirine has no creatinine clearance cutoff.

And there - there are numerous others. And you can basically just list them out and have a conversation with the patient. And the nice thing is it's not something that's going to have a negative impact because they're likely going from one pill to one pill or one pill to a long‑acting injectable.

Dr. Gruta: So, I'm going to play your patient, Dan, and I'm going to say, "But Dr. Moring‑Parris, I don't know if I want to deal with new side effects." Let's say we - I, you know, I go with... What is it? Rilpivirine, dolutegravir, or whatever you want. Yeah, that one. Let's say I choose that one. What are the things I need to look out for? Do I need to tell my other doctors about it? Is that going to have any interactions with my medicines, my diabetes medicines, my hypertension, and my statin that I'm taking?

Dr. Moring‑Parris: Yeah. So, luckily, the medicines that we talked about today are generally don't have any significant interactions with the medicines you're taking. I always do a thorough interaction check before even making suggestions about switches. And it's always good to let your doctors know that you're on a new medication, but I don't anticipate any specific issues regarding your other doctors.

And then in terms of side effects, additionally, we're lucky in that the newer meds that I've discussed are really very similar in their side effect profile. Obviously, if we were talking about the long‑acting injectable, there are some specific side effects related to injection site discomfort and sometimes a brief flu‑like syndrome that tends to get better over time. But in terms of the co‑formulated dolutegravir/lamivudine or dolutegravir/rilpivirine, they're really quite similar. And although there's always a possibility for an unanticipated side effect, I don't expect anything significantly new. If there is something, certainly, let us know. And the good news is that it's - we have more than one option. So, if you do end up not tolerating one of these, we can talk about switching to another one.

Dr. Gruta: Great. Okay. I'm going to put back my provider hat and just comment also that don't forget to ask your patients also about over‑the‑counters that they might be taking that is not necessarily included in their med list. They should technically be included in their med list, but you know, it's always hard to be on top of everything. So, it's always imperative to review your patient's med list with them every time you see them, including over‑the‑counters and including supplements that they may be taking. There's a lot of people out there who are taking supplements. And just, you know, make sure, I mean, this was - is probably the same teaching they had with taking the bictegravir‑based regimen that they need to separate that from divalent and polyvalent cations. So, if they're having heartburn, you don't want to be giving them aluminum or magnesium‑based antacids at the same time as taking their integrase‑based regimens.

The other thing to remember is that rilpivirine requires an acidic gastric pH. And so, any oral rilpivirine regimen should not be co‑administered with antacids together.

And also, it is contraindicated to coadminister proton pump inhibitors. So, omeprazole, pantoprazole, all of those medications when somebody is taking an oral‑based rilpivirine regimen. Obviously, if they choose to do long‑acting injectable cabotegravir/rilpivirine, those antacid requirements go out the door, meaning that they're free to take them whenever they wish, just because we are now bypassing the gastric, you know, absorption issues and the acidic pH is not applicable when you're giving the long‑acting injectables. So, I wanted to just put that out there.

And then also, just to, you know, just to comment real quick, Dr. Moring‑Parris, that while the dolutegravir‑lamivudine option is fair to consider, it is off‑label to give it to somebody who is - whose creatinine clearance is below 30. So it like a shared decision‑making should be there. Should - you should engage in shared decision‑making when considering that option. The reason why it's clinically fair game is because lamivudine, the component that is technically supposed to be dose‑adjusted below a creatinine clearance of 30, is so benign that there are many people who still continue at this despite the drop in creatinine clearance.

Dr. Moring‑Parris: Thank you. Yeah. And there are actually newer drugs that can be considered in the mix as well that I didn't mention. So, one that's available in the United States currently is doravirine and islatravir. So, doravirine obviously has been around for a while, very favorable side effect profile. It's an NNRTI, and they've combined it with islatravir, which is a new first‑in‑class non‑nucleoside reverse transcriptase translocation inhibitor, NNRTTI, and it's a single‑pill, a daily formulation that has an advantage again of being tenofovir‑sparing. So, a good option for patients in this scenario.

It may be somewhat limited in that we don't yet know if it can be used effectively in patients with M184 mutations, V and M. So, just something to be aware of just because that mutation is somewhat common. But again, doravirine/islatravir is something that you could consider in a patient who you're switching due to renal concerns.

Okay. Shall we move on and talk about a second case, Dr. Moring‑Parris?

Dr. Moring‑Parris: Yes. Sounds great. Let's do it.

Dr. Gruta: Okay. All right. Well, this was a type of case that the HIV warmline where we work, Dr. Moring‑Parris and I work, where we receive calls from provider - HIV providers around the country, and we help them through clinical scenarios, like antiretroviral switching is - is one particular topic we might be helping them out with.

So, this is a case about a 63‑year‑old man who's been living with HIV since the age of 37. He recently transferred his care from a different state about three months ago to the caller that's calling us about this patient now. The patient has a completely undetectable viral load with really robust T‑cells of over 700. He's been on the same antiretroviral regimen since 2008. So, it's now 2026. So, almost two decades on this same regimen. And the regimen consists of raltegravir 400 mg twice a day, darunavir 600 mg twice a day, ritonavir 100 mg twice a day, and etravirine 200 mg twice a day.

So, just for folks who may not be aware of the classes that these come from, so, the raltegravir is an integrase inhibitor. It's was actually the first integrase inhibitor available on the market back in 2007. And then, of course, as I alluded to earlier, darunavir is a protease inhibitor, seems to be our most commonly prescribed protease inhibitor in clinical practice. And then the ritonavir is there to boost the darunavir because we always need darunavir to be boosted. It's never given unboosted. And etravirine is a non‑nucleoside reverse transcriptase inhibitor. And all of these BID‑dosed.

We don't exactly know. You know, we don't - his old records from the provider, from the other state has not yet quite caught up to the current, the new provider. But what information is available does say that this patient has resistance mutations that were detected back in 2007 and it included some kind of significant mutations to both NRTIs and one - and the first‑generation NNRTIs. So, in particular, he developed K65R, M184V, 210W, M41L, and K103N.

So, we don't expect our audience to be able to like know off the tops of their heads what does that mean, but the bottom line here is that this patient seems to have developed broad NRTI resistance from prior regimens that he's taken. So, nucleoside analogues like, you know, starting off with AZT, lamivudine, abacavir, tenofovir, lamivudine, emtricitabine, and then the K103N mutation confers resistance to first‑generation NNRTIs. So, makes me think that this patient was likely on an efavirenz, tenofovir disoproxil fumarate and emtricitabine regimen at some point in time to have had this particular resistance history.

This comorbidities of this patient include diabetes type 2 diabetes, hyperlipidemia, and hypertension. Not a big surprise. He's now in his early 60s. This patient's comedications include atorvastatin. Also, an empagliflozin seems to be very common. Semaglutide, losartan, and amlodipine. So, not too different from Dan's patient from the first case that we went over.

So, at the last visit, this patient actually told this provider, "I'm so tired of taking so many pills. I keep getting new ones, especially now that I have diabetes and I have hypertension. - is there a way that you can make my ARVs easier? Because all the other medications I'm taking, I only take them once a day. But I know I have a really resistant virus, so I don't really know if that's possible. And then I've also heard that something in my medication, something in my ARVs, maybe also contributing to - my high cholesterol. Is that true, Doc? And if so, I want to change up. Can you tell me more about what my options could be?" Dr. Moring‑Parris, how would you approach this patient?

Dr. Moring‑Parris: Yeah. So, certainly, this patient does not need to be on so many medications, right? You know, I think you have pointed out the historical perspective that there probably was a time where this made total sense, but in - in hindsight, you know, it seems a little excessive and unnecessary. And, you know, the patient is correct that, you know, if possible, it would be nice to avoid, especially some of the older protease inhibitors in a patient with, you know, metabolic issues like this. And, yeah, luckily, this is a situation where we, you know, if we do need to use protease inhibitors, we can use once‑a‑day, you know, co‑formulated protease inhibitors, like darunavir/cobicistat. We have the second‑generation modern integrase inhibitors like bictegravir and dolutegravir that are also usually daily unless there's integrase resistance and you're using dolutegravir, which would prompt you to use it twice a day in the face of certain mutations. And then we have, you know, our novel agents, lenacapavir, and the new integrase inhibitor, cabotegravir. So, I think there would be a lot of potential options. And can you remind me the NRTI mutations in the specific patient?

Dr. Gruta: Oh, he has plenty. He has K65R, 184V, 210W, M41L.

Dr. Moring‑Parris: Okay. Yeah. So, patients like this, you know, you want to be more hesitant to use a tenofovir‑based regimen. You know, when we have M184V alone, there's good evidence that using - continuing a tenofovir‑based regimen is likely very effective. But would you - would you consider something like daily dolutegravir with co‑formulated darunavir/cobicistat in a patient like this?

Dr. Gruta: I certainly would think that that's fair game. And, you know, I mean, just to kind of step back a little bit here, it sounds like this patient, just from a shared decision‑making perspective, they are the ones asking for change. They are the ones who are - who have identified that they are not satisfied with their current regimen. And I'm shocked it took him this long to recognize that he could - or - yeah, that he could have had it better a long time ago. But maybe, I mean, we don't want to throw shade at the prior provider because we have no idea. Like maybe they've had those conversations, and maybe at the time the patient was not ready because, you know this clearly, if this patient has been diagnosed since age 37, he lived through the worst of the epidemic when people were dying left and right, and we didn't have good regimens. And so, a lot of times, when people find their first regimen that they become consistently suppressed on, they don't want to - they don't want to make a change. And so, we want to - we want to point out to the patient that since 2008, like darunavir doesn't - if you, you know, especially if there's no protease inhibitor resistance to - or darunavir‑related mutations that he's ever developed, that there's no reason why he couldn't take that once a day, for instance.

Since 2008, the family of integrase inhibitors has evolved and we've developed much more potent second‑generation protease inhibitors that are given once a day. And - and so that - so we have room for movement there.

And then we've also since - noted in the interim between '08 and '26 that you don't need three fully active agents to keep somebody suppressed. I think right now our mantra is like, as long as there's two fully active agents one of which, or both of which have high barriers to resistance it's - it's almost always enough. So, for instance, darunavir has a high barrier to resistance. And the second‑generation integrase inhibitors like dolutegravir or bictegravir have high barriers to resistance.

So, is it even necessary to have that third class - the NNRTI etravirine in the mix? And I think that both Dr. Moring‑Parris and I are in agreement that, "No, that is like way too much." And so, - one of the options Dr. Moring‑Parris put out to the front here is boosted darunavir with cobicistat, and then dolutegravir. And yes, I would say yes to that. You know, and if we - if we can get the rest of the patient's history or old records, and we can get further corroboration that there are no other resistance, that no other classes have been knocked out aside from essentially the NRTI class, and then the first‑generation NNRTIs.

This patient is also a candidate for long‑acting injectable cabotegravir and rilpivirine. So, if this patient wants to - like get off pills altogether for their HIV medications, that is fair game as well. And then we certainly can discuss also the option of oral rilpivirine and dolutegravir if he doesn't want to do long‑acting injectable again with corroboration that there are no other mutations that confer resistance, for instance, to rilpivirine. That is also an option, I believe, for the patient.

 And the only reason why we kind of pause on, or perhaps would not want to recommend dolutegravir with lamivudine is because he does have a 184V, and then if he has a 184V, then dolutegravir would be the only active agent on his regimen. And that - that obviously, we don't - we don't only want one fully active agent, we need something - some background activity.

Same goes for the doravirine/islatravir option. While the doravirine, again, if there's no other resistance that we can find in the NNRTI class from old records, the doravirine could potentially still be fully active. But then early data seems to suggest that we need to pause.

Well, actually, Dr. Moring‑Parris, correct me here because he has both K65R and M184V.

Dr. Moring‑Parris: Yes. Great points. So, yeah, the - the K65R seems to induce hyper susceptibility to islatravir, and it makes the M184V kind of a non‑issue. So, a little more nuance on this drug, and this might be a good option. Again, this - it's a new drug, and we don't totally understand everything, but especially because he's already virally suppressed, I think that likely would be a potential option.

Dr. Gruta: Yeah. I mean, it's obviously discussion again, when it comes to shared decision‑making, we want to present to the patient that, "Hey, this is what we know about this medication or this particular option is that it was studied in people with - with suppressed viral load like you but we are still, you know, sort of in the early stages of like understanding what the mutations that you have, you know, how it impacts it." And as Dr. Moring‑Parris said, there is encouraging preliminary data to suggest that if there's both K65R and 184V, that it will be very active. But , it's a very new combo, and so we want to make sure that the patient is aware that perhaps not all the data are there yet to inform going to that particular option.

Okay. And then just in terms of the patient's concern, we want to also recognize - I actually would applaud this patient for like asking like, my current regimen, is it potentially contributing to some of his conditions? Potentially. So, you know, like the - like ritonavir‑based regimens we know can contribute to dyslipidemias, but he is of, you know, of an age where dyslipidemias occur. And also, it's, you know, we're giving statins to, or at least that's the recommendation now, we give statins to most patients with HIV who are over 40 years old. But so that - that might be an unavoidable consequence.

But speaking of which, if he - we are going to put him on a switch him, Dr. Moring‑Parris, to darunavir/cobicistat plus dolutegravir, as an example, luckily, we really don't have to make too many adjustments with his co‑medications because his prior regimen was actually already a boosted regimen. And so, if his medications were dosed correctly with the - with the regimen, the ritonavir‑boosted darunavir that he's on now, then we don't need to make any switch. I don't foresee making any further dosing adjustments if we - if he switched to the cobicistat‑boosted darunavir with dolutegravir.

So, there's a lot of nuances here. I just wanted to kind of demonstrate for you all sort of like the, you know, the - the thought process that Dan and I like individually go through when we care for our own patients, but also, it's very collaborative. You know, in my clinic, I definitely have these conversations with providers, and I'm sure Dan has also discussed situations like this with other providers, but also this is sort of an example of a discussion we would have in our - in our consultation center of cases such as this. Okay.

Dr. Moring‑Parris: Yeah. I would just also say to something that's probably pretty obvious to people, but it is really important, I think when you're going into a conversation like this, at least for myself, to do a little bit of preliminary work to have in my head some of the options, because I definitely - have jumped the gun before and said, "Oh, hey, let's switch you. We can do a single pill." And then the patient says, "Oh, yeah, let's go for it." And then I look in the chart, and I see some drug interactions, and I realize I have a mutation I didn't remember. And then I say, "Oh, maybe we actually might need to do two pills," or, you know, so I think it's helpful, at least for me to - to do, you know, check interactions, review genotype, get kind of like a mental list of some options. And that way, if the patient bites on your pitch to - to simplify, you're kind of ready to go, and you don't have to end up kind of backtracking once you take everything into account.

Dr. Gruta: Really good point, really good point.

Yeah, we have a question from Nhung[?]: What would you recommend for a patient who came from Africa recently and is diagnosed with HIV, but totally forgot about their regimen in a war case? Please make sure the new prescribed is up to date.

Dr. Moring‑Parris: I'll - I'll take a stab. So, these are - these are tough. You know, when people are coming from other countries, it sounds like a traumatic scenario where someone may not remember what they have been on before. And a lot of places in the world also they don't do genotyping. So, that might - that is likely something that you won't be able to get. And if they've been off of meds for a while, certainly it's helpful to get a genotype at entry to care. But it will likely be a wild type and may not show you mutations that have - that have arisen in the past while taking medications. So, you know, do the best you can maybe show - show medication pictures, you know. Sometimes, if you find out what country they're from, you may be able to look up what is sort of the standard programmatic medication in that region. You know, a lot of places - in the world, put everyone on TLD, tenofovir, lamivudine, dolutegravir. But sometimes you can, like, look up at the WHO what they're doing in that region. And that may be a clue. But if you really cannot find anything, sometimes you might just have to - to take a risk and - and prescribe something that, you know, is - is generally highly effective, like co‑formulated darunavir/cobicistat/tenofovir/emtricitabine or bictegravir/tenofovir/emtricitabine, and then very closely monitor them. And if it - if it doesn't work, that would be a great time to get an on‑treatment genotype to see what mutations have arisen. And then you hopefully will get lucky - and one of the - the highly effective regimens does work. I don't know if you have anything you want to add to that, Dr. Gruta.

Dr. Gruta: Oh, yeah. Excellent approach, Dr. Moring‑Parris. The other question to ask is: how consistently do they have access to meds and how consistently were they taking their medications? Because as we know, especially in a war‑torn country, you may not always have access to medications. It's one thing if they stop medications altogether. So, they're on - if they're on it, they're on it consistently. And if they're interrupted, then they just stop altogether. what bodes for perhaps potential resistance is more when they're on‑off, on‑off. So, or maybe trying to stretch out their supply and maybe taking three or four doses of whatever they're on a week versus taking that - taking it every single day.

So, that might also impact my decision‑making because if that was their pattern of taking their medications, I - I would maybe add something else to the darunavir/cobicistat/ tenofovir alafenamide/emtricitabine coformulation. I might add a doravirine to that, for instance, or I might add, you know, an integrase inhibitor like dolutegravir to that.

Excellent question. Thank you for that question, Nhung.