Dr. Gilleece:

Achieving the Potential of ART

So we're going to move into the next section of today. And it's talking about achieving the potential of ART. So we've got 3 cases here that we want to take you through just to think about the potential of ART to treat people living with HIV in different scenarios.

So before we start, I'm going to start for that kind of headline again. I'm going to start at the end and work backwards, just Dinah and then come towards me.

So panel, we have really many highly effective ART options. But what are the skills that we need in our healthcare professionals to make sure that actually we can give the right ART to the right individual? So I'm going to start with Justyna, your—your headline.

Dr. Kowalska: Well, you need to learn how to listen. I mean, we have a frames of a recommendation. So this is a fair judgement of evidence, what's the best options. But these frames still have a lot of different colors. And for me as a physician, they are more or like—or less the same because they are all extremely effective. But for people, there might be slight different changes—differences between them that—that—that matters.

So—and it's so difficult to individualize nowadays because I mean we all here remember the beginnings and that it was either having a diarrhea all of the time or having a rash everywhere. But now, now it's—for me, it's perfect. And it's important to remember that it's for me. This is my perception. It's not our patient's perception. For them, this is still the world that they need to take in.

Dr. Gilleece: Okay, great. Thank you, Justyna. Angelina, your headline for this? What do healthcare professionals need?

Angelina Namiba: So I have a few—some. I think for me I'm going to focus on the human skills. And I know what I'm going to say is not rocket science. And I'm sure the healthcare providers in this room already practice this, but I'll share them very quickly anyway.

I think the first set of skills required is being perceptive, the human skills, being able to do the motivational interviewing, but more importantly, from a patient's perspective, just being honest and acknowledging where you have limitations. Because we know doctors are also human beings. So that's a really important skill.

I think the ability to ask the right questions, and I know that doctors and healthcare providers are trained to ask questions to diagnose and then to treat. And yes, that's the key thing. But I think sometimes if you just focus on the diagnosis alone, you could miss some of the nuances of a patient's life, which might make the diagnosis even better. So being able to just be a bit flexible in that.

I think I'll agree with what Justyna has said in terms of listening, but I would go a step further to say listening without bias, without diversion, without interruption. So listening to really hear. And the last one I'm going to say is we know—doctors know what the best regimens are for us on the most part. But I think being able to be flexible and to accept that as patients, we also know what works for us in terms of our goals, in terms of our circumstances.

But I have to say that the—most of the doctors I know already do this, so there's only a few number that don't do that.

Dr. Gilleece: Great. Thank you. Our headlines are getting very long, but all very important and agree with everything that's being said.

Angelina Namiba: They’re all important.

Dr. Gilleece: No, no, no. Absolutely, absolutely. Dinah, what works for you for healthcare professionals to make sure they give the right ART?

Dinah Bons: Yeah, I think most have been covered. But for me now as well to say is like, I think the flexibility and the understanding that you have a sort of like an almost a relationship with your patient so that you have sometimes more information about what culture do you come from, what kind of religion maybe is important to you? You know, only having that kind of information might also help the person to be more in contact with the healthcare system. So people with a migrant background have sometimes different views on religions as well.

So for example, they have like their cultural heritage in it. And as long as you acknowledge that and maybe have that integrated in your contacts, it might be that all the different things that I've already heard are maybe somewhere more meeting each other, and that there is not a distance between it.

Flexibility is also very important. Just short. I'm sitting here. Tomorrow, I need to get my long injectables, which is not happening because I'm traveling, and I just made a call to the Amsterdam Center for AMC and they said, like, okay, is it possible to—on Wednesday. Said, no problem, you're doing important work. So, you know, that is also very important that you have that flexibility at the moment when you have that relationship.

Dr. Gilleece: Great. Thank you, Dinah. Jürgen?

Dr. Rockstroh: Yeah. You know, I think healthcare providers are not necessarily trained for that kind of conversation, and—and—and that means that you sort of have to self-teach yourself a little bit of how you deal with different personalities, and not everyone is that upfront in a first meeting to say, this is how I live, this is how I go to bed, this is how I work. This is the drugs I'm using.

I mean, it takes—so you really have to leave room and sometimes, you know, even say, well, maybe we're going to just think about this and come back with your questions and we talk again to really make sure that you don't end up with this sort of, well, this is going to work for everyone, but I'd rather have an individualized approach which sort of reflects on the different base characteristics.

And I always see that also with adherence, where people are not taking the medicine, you have to understand why are they not taking it? What is the reason? Then you understand, oh well, because I'm drinking and I like every evening. I'm so boozed I can't take any drugs anyway. Well, then you have to think of something which fits into that kind of pattern. And don't be judgmental. I think that's one of the most important things to sort of leave room for all kind of people to express themselves and then, you know, tailor your responses accordingly.

Dr. Gilleece: So a holistic approach to. Yeah. And would you use different team members to try and help you find out what's working or what isn't working for people?

Dr. Rockstroh: Well, you—I—I think that—I mean, obviously, you know, in the UK you have your peer support, which is fantastic. Unfortunately, outside of the UK, peer support is very rarely present. I know it works in trans—in clinics in Thailand, for example. All work with peer support. Unfortunately, in Germany, we don't have a lot of peer support and psychology support is little, but we do have NGOs and that can be very helpful because particularly for migrants, if you have like we have migrant, which is kind of a peer support, which help and speak the same language, because don't forget that we also have language barriers which need to be overcome. And that really is very helpful.

Dr. Gilleece: Absolutely. Sophie, what do you think is important?

Sophie Strachan: I mean, everybody's covered it, to be honest. And let's just save time because everyone's covered it.

[01:06:20]

          Pretest 3

Dr. Gilleece: Okay. All right. We're going to move on to our pre-test question number 3 for this section. So you the audience an online time to get voting. So what is your approach when a person who has experienced long-term and continued virologic suppression on their current ART regimen, but previous NNRTI failure with resistance expresses interest in switching to a different regimen? Do you:

1. Keep the focus on the available safety and efficacy data related to potential switch options;
2. Make the change without too much discussion of data so they feel supported;
3. Have an open discussion to learn which needs are not being addressed by the current regimen; or
4. Focus on supporting them and maintaining their current regimen. Because virological efficacy is too important to risk with a regimen change.

Vote now. Oh, that was quick. Is that all our answers in. Okay, so most of you gone for C. You're going to have an open discussion which needs—where needs are not being addressed by the current regiment. I think really important. Okay. And we'll go on from there.

[01:07:32]

          Quick Panel Survey

So we've done this.

[01:07:35]

Key HCP Skills for Optimizing ART

So the key skills that we think really for optimizing ART are listening, so thinking about motivational interviewing. We want to think about individualized care. So look at the person in front of you and talk to the person in front of you and ask them what they need. And then the additional skills might be you might need the ability to do a rapid start. If somebody wants to start clinic that day in clinic. You need to be able to follow people up virtually or how they want or have that flexibility that Dinah was talking about. But you also need to have that whole team approach. And I think we'd all agree that they're the really key things.

[01:08:06]

Achieving the Potential of ART: Case Discussions

So now we're going to have some cases. We're going to have 3 cases.

[01:08:11]

Case 1: New HIV Diagnosis

And I'm going to start.

[01:08:12]

Case 1: Newly Diagnosed Person Ready to Start ART

So I'm going to start with case 1, who was a newly diagnosed person ready to start ART. So she's a 45-year-old woman. She's migrated from Zimbabwe to the UK 6 months ago. She herself works in a hospital and is worried about confidentiality. She tested routinely in the emergency department and was very shocked by her result. She would like to have more children.

Her HIV is subtype G. She has no comorbidities when you first see her, but you do an IGRA test which is positive to suggest possible latent TB, and then she has lymph nodes on her chest. Cut the long story short, basically she has a bronchoscopy. She doesn't have TB. She has latent TB, but she might have sarcoidosis.

[01:08:57]

Panel Discussion

Okay, let's focus on HIV in starting treatment. So I'm going to start down the end with Justyna and Angelina. So when somebody is starting treatment, what do you think are the long-term safety and efficacy things you need to think about if you were talking to this woman? Justyna as a physician, Angelina as a peer mentor.

Dr. Kowalska: Well, as a physician, for me, it's always the drug-drug interactions when you need to treat different—a bunch of diseases at a—at a time. I'm also thinking we are now in a very good times when we finally got rid of any presumed risks for dolutegravir. So, I mean, the choice would be easy, but we should expect that that kind of struggle would always remain. There will be future challenges.

So yeah, as I said, as a physician and for now, I would like to make sure that the—the drugs I am giving together, they are not influencing each other in a way that they are less effective because there—there is a potential of many life threatening infections here.

But of course, I would like to also eat a cake and have a cake. So I would like to give the regimen that would hold for a long time, because we know that people are attached to what works in the beginning, and we know how—how sometimes it's difficult to make someone take a different pill because we believe it's safer, but they like the one that they started. So this kind of wakening[?].

Dr. Gilleece: Okay, great. Thank you. Angelina?

Angelina Namiba: I guess looking at your lady, I mean, this is somebody who's having to navigate a new country, a new job, you know, thinking about her future, new colleagues, etc. I think for me, the simplest thing, the answer is it should be something that is very simple, something that is safe, very few side effects, because those key things are going to be the ones that are going to play a critical role in how even starting the treatment, staying on it and adhering to it. So something very simple and safe to take.

Dr. Gilleece: Absolutely. Completely agree. And I think—I mean we have lots of guidelines about shared decision making. I think it's also very important to understand that she is in that position where she's just been newly diagnosed. She not—may not be able to hear everything you're saying to her because she's really in shock. So it is about understanding about what information is taken in and—and how she feels about that information. That's really, really important. So it's getting—getting that feedback from her as to what she's understanding by saying to you—by what you're saying to her.

I think as well as obviously she may have comorbidities and drug-drug interactions, thinking about the other things Sophie in her life that she might need to think about, she's—she works in healthcare. What are the other things you might need to think about for her?

Sophie Strachan: Yeah. So I think if I was approaching this from, like, a peer support role, I mean, one of the things that I always do to anyone that's newly diagnosed is to give them access to resources like your rights as an employee and your, you know, right to confidentiality and who she could speak to within the hospital and just that peer support element of, you know, it's really important that they understand their rights. She's new to the UK. She—you know, she's navigating a healthcare system that she won't be familiar with.

And, again, in terms of the—I mean, co—the co-infections with the latent TB.

Dr. Gilleece: So that's drug-drug interactions.

Sophie Strachan: Right.

Dr. Gilleece: So that's what Justyna was talking about potentially.

Sophie Strachan: Okay.

Dr. Gilleece: Depending on the drug use.

Sophie Strachan: So then—so then it's also factoring, you know, the pill burden and stuff like that.

Dr. Gilleece: Yeah.

Sophie Strachan: So yeah, but I would just be looking at it really holistically and from a peer element, it's just really for her to be aware of what her rights are and where she can go if she has any concerns.

Dr. Gilleece: No, absolutely. And I think that is key. And that's something that we're seeing more commonly certainly I think as populations are moving due to war and various other reasons in Europe, I think as well, working in a hospital, she's probably doing shift work as well. So it's that discussion about pills and when is a good—time to take them really basic stuff, like what will work when you go from night shifts to day shifts and you're looking after children or you're, you know, caring for somebody else, you know, somebody who you are a live in carer for.

So I think there's lots of issues in that—in—in that particular situation that we can—we can draw on from the panel. So thank you for that. I'm now going to hand over to Jürgen for our next case.

[01:13:45]

Case 2: Potential Switch With Virologic Suppression

Dr. Rockstroh: I also think that if someone's really very shocked about the diagnosis, the question always is also, do you have someone you can talk with about that? Because sometimes we—we forget that they don't have anybody to talk this about. And then to sort of, you know, connect them with people in a sensitive way where that's possible because confidentiality is such a big thing, and many people from a certain country don't want to meet people from another—from a similar—you know, from the same country, because they're sort of afraid that that will then spread. So it's a very challenging, this initial moment of diagnosis and—and dealing with that.

[01:14:19]

Case 2: Person With Virologic Suppression but Misses Occasional Doses

So I have also prepared a case. This is a 37-year-old transgender woman who was diagnosed in 2018. History of several STIs, resistance tests shows no resistance mutations, subtype B. Started B/F/TAF, CD4 count increases. Viral load goes down. All good. She works as a flight attendant and obviously has the issue of flight attendants have frequent time zone changes, unpredictable work schedules. And so she says she sometimes does miss doses, and she's kind of interested in switching to a long-acting ART regimen.

You see some of her other baseline characteristics there. So let me ask, Justyna, is there any other additional information you want or what would you do?

Dr. Kowalska: Yeah, of course we need to—I would ask about the HBV. So hepatitis B infection status for—luckily for younger generations is not the case. So with the time I think we'll be free of that questions. But now in Poland, at least if you are 25 or older, it is still applicable.

Dr. Rockstroh: Great point. Now so since it's a transgender woman, would there be special things you would want to take under consideration or you feel should be asked, Dinah?

Dinah Bons: So yeah. Obviously you’re still –

Dr. Kowalska: Looking at me.

Dinah Bons: For the answer. No, no, no, definitely. I think for the transgender woman who works as a flight attendant, there are so many things about social—societal oppression, societal, you know, like people might be bullied at work, people might be not feeling safe always everywhere on the world. So I would say there is just this conversation about the different things that a person might—might occur to them during the day and doing this job.

I would definitely go into more into that space as well, to see how much of that emotional support would you need, maybe from someone else than the—than the person sitting next to you? But you have a colleague that is a good psychologist, or maybe there is another person that is a social worker. So you can sort of like tap into that. And I would say like, yeah, maybe that is missing.

[01:16:35]

Case 2: Person With Virologic Suppression—Digging Deeper

Dr. Rockstroh: All right. So make a few suggestions here and support that might be helpful. Pill box in the luggage, ask her to share a bit more about the challenge, was taking her medication. And indeed, she admits that she's nervous about having HIV medications with her while traveling through countries with discriminatory LGBTQ laws.

She also notes that she continues to struggle with a daily feeling of stigma every time. She takes her antiviral therapy, something which we see quite commonly in many different individuals living with HIV.

[01:17:07]

          Panel Discussion: Would LA ART be a better option or not?

So obviously the question here is would LA be a better option or not? So under consideration of the missed occasional doses you've seen, is that—would that be an option for you? Would you still say a 3-drug regimen is better because maybe higher genetic barrier or what would be your thoughts around that?

Dr. Kowalska: Well, I think that ultimate goal is that we sustain the therapeutic level of a drug. And the way that we get there—and this is the most important in terms of the resistance barriers. But also I tell my patients that, you know, the long-acting injectable, they free you from pills, but they bind you with us. So also for—you know, they need to come. It's no longer any other solution.

So that kind of consideration as well, because it doesn't matter. I mean, of course, we know now that we have a very good in terms of pharmacokinetic and the genetic barrier drugs, but still they need to be taken. So everybody needs to make this balance in their head, whether I will be able to take, so to say to them, even the injectables.

Dr. Rockstroh: That's true. So—so thinking about the role of stigma and ART adherence, Dinah, in that context, would you say that—that in the transgender community, these whole travel bans and—and these issues around the laws, is that particularly true for this population?

Dinah Bons: There are 2 things about to say about this. I myself have been living with HIV very long, so I know the travel ban and what it did for me for coming and going forward to the US. So that is in the collective memory of many of us. On the—on the other hand, pills in your house can be sometimes even dangerous, right? If people find that and then start to—start to talk about it amongst each other.

So to not have that still—you know, like it's not in the house anymore in my house at least. So I'm feeling way more happier to invite people over to—to be freely saying like, oh, just take a cup from the cupboard, it's in there because previously I also hid it in the kitchen. There's nothing to hide anymore. And that is for me, really—and for many of my community members, something that is a relief. It's not that we know—we don't know that we live with HIV, but it is that you just have something where you're not remembered every time about all these things that that are not positive.

[01:19:50]

          Case 2: Person With Virologic Suppression—Digging Deeper

Dr. Rockstroh: Yeah, that’s—that's a great way of framing it. So let me just give some of that background hepatitis information. And you can see that she was HBS antigen negative. No sign of call it hepatitis B DNA was negative. But there were anti-HBC antibodies which showed that there was a past infection. So you see. Now would you be worried in the presence of just having anti-HBC that under long-acting regimen with—with any note, tenofovir that could be a concern or?

Dr. Kowalska: I mean, we know that 99 out of 100 this is not an issue. But still I would have a share in—in terms of sharing decision, I would let the patient know that, you know, for me it is not considerably—considerable, but—but.

Dr. Rockstroh: Yeah, I completely agree. I—I think the risk is very low, but nevertheless, I think we just have to be more aware, as we're increasingly using tenofovir-free regimens, that this could be something to at least lead to some signaling or some sign of HPV replication.

[01:20:52]

          HBV Viremia After Switching to LA CAB + RPV in Retrospective Case Series of HBsAg-, HBcAb+

And there was a recent study presented, which looked at 149 individuals who switched to long acting and there was a high proportion of individuals who were only HBC antibody positive. And of those and that was 25%, that's pretty much the frame which we're talking of that resembles with other cohorts as well. And there were 3 individuals who actually did develop low level HPV viremia.

Now none of them developed a flare of hepatitis. There was no increase in liver enzymes. They didn't become HBS antigen positive. So the question is does that mean anything clinically? I think we don't know. But I think it does tell us that if we switch someone off of protective tenofovir environment, then at least we should do intermittent control of HPV serology just to see if something's happening and do liver enzyme measurements, just to be sure that there is no signal of HPV activity.

And then most importantly, I think what we should forget is that in case cancer becomes developed or something and you have immune suppression, then that's where your real risk is for more severe reactivation.

[01:21:55]

Case 3: Potential Switch With Virologic Suppression

All right. I'll hand it over to Justyna for her case.

Dr. Kowalska: Thank you. And we are running out of time, so I'll try to speed up a little bit. And this is a cisgender woman who is already living with HIV 31 years.

[01:22:20]

          Case 3: Older Person With Viral Suppression on a Boosted Regimen After Previous Virologic Failure

So really—sorry—in my head already. So living with HIV and also being expose—exposed to different drugs for many, many years. She's 58, which is important, young as all of us. And so she acquired HIV through heterosexual contact. And she is a little bit overw8 in terms of comorbidities. She was cured from cervical cancer. She’s had—she's had menopause, dyslipidemia and type 2 diabetes.

She is otherwise managed to quit smoking but just 2 years ago and works in an office with the lowest physical activity. So that's the major picture.

And looking into her antiretroviral treatment, this is actually the treatment of my whole occupational history as well. We started with—I'm not sure if everybody remembers the ddI-d4T-3TC. It was really a very toxic mix. And she was unfortunately having that, and in the course of it, very quickly developed lipodystrophy.

We were aware very quickly that these regimens can do it also that 3 NRTIs are not a good idea. So she was switched to efavirenz-based regimen and added abacavir at that time. And I do remember these times we did not have HLA testing. We just had to provide the patient with the drug and just, you know, wait and pray. And she actually developed luckily not severe hypersensitivity reactions. So we switched her of—with tenofovir. That time we were lucky to already get this treatment. But she experienced virological failure again.

At that time we had no resistance testing. So it looks like I'm making this case especially difficult. But this is life. It's—it's a real life.

So finally she is on darunavir boosted with cobicistat for a sake of the number of pills and dolutegravir. And again, there was a trend towards having such solutions, I think, around 6 to 8 years ago. And so the question is, what should I do with—with this situation? Should I actually try to get rid of, let's say, booster? We know it's not good to have booster with aging. Yvonne, what do you think?

Dr. Gilleece: So I think there's multiple reasons to change her antiretroviral regimens. So she's a postmenopausal woman. She's got multiple—she's got comorbidities with dyslipidemia and type 2 diabetes. So first of all, talk to her about a statin if she isn't on one already. Looking at darunavir and cobicistat. So we know from the DAD study that darunavir associated with an increased cardiovascular risk. She has multiple cardiovascular risk factors, including being an ex-smoker. Therefore, this is not a good combination for her as she goes into older age.

I know 58 is not old but older age thinking of the long term. The other reason as well is, so simplification. So she's on multiple pills. So you could give or potentially a single tablet regimen. We know from other studies, such as ERNEST and newer studies as well, suggesting recycling of nucleosides in the face of previous failure can work in the context of using another agent so such as dolutegravir, bictegravir or a protease inhibitor. But obviously in this case you want to try and get her off protease inhibitor.

Also, thinking about longer term, you want to think about polypharmacy. This is a woman who's 58, multiple comorbidities. She may need other drugs, not just statins. In the longer term, thinking of her type 2 diabetes and anything else, you may well develop hypertension. So there are lots of reasons here to think about switch, but all of these need to be discussed with her to explain why it might be a good idea to switch, and then to think about what you might switch to with her.

Dr. Kowalska: Yeah, exactly. That's a very good question. And what do you think, Jürgen? What would you offer her?

Dr. Rockstroh: Yeah. Well, if—if we have that kind of conversation. And she said she would be happy to switch and I would agree with the increasing number of other co-medications, the risk of drug interactions is very high. I would—I would feel comfortable having that conversation because I think we do have options here in the setting of efavirenz, TDF-3TC, I would at least presume in the lack of a resistance test that there was a K103N and M184V. The—those were the 2 mutations which appear the fastest.

That would be the likely scenario, but that would mean that if you would put her on B/F/TAF, that would still probably work, because in the label—at least in the American label, you can do that in the presence of the M184V.

Another option could be dolutegravir plus an NNRTI.

Dr. Kowalska: Yeah, sure.

Dr. Rockstroh: Because there are NNRTIs which are still fully susceptible in the presence of a K103N, and just having a efavirenz, I find it unlikely that she's going to have a lot of other NNRTI mutations. So that would be my 2 options to discuss.

Dr. Kowalska: Okay. Our take home message.

Dr. Gilleece: I guess the take-home message from this—so from that particular case is you need to think about the person sitting in front of you. And there are lots of—there are more than—there's more than one right answer, as you've seen here. So it's just having that discussion with somebody, showing them the pills, talking through the side effects, and then working with the—with the individual to try and decide what's the best thing.

[01:28:05]

          Posttest 3

So I'm going to bring today's session to a close. But before we do here's your post-test. So what's your approach to a person who's experienced long-term and continued virological suppression on their current ART regimen, with previous NNRTI failure and resistance expressing interest to switch to a different regimen? So you answered this before. Let's see if there's been any change. So

1. Keep the focus on available safety and efficacy data related to potential switch options. I'm sure you're all sick of my voice. I am.
2. Make the change without too much discussion of data so they feel supported;
3. Have an open discussion to learn which needs are not being addressed by the current regimen; or
4. Focus on supporting them and maintaining their current regimen because virological efficacy is too important to risk with a regimen change.

Vote now online and in the auditorium. Great. Hopefully, that'll be the last time you'll have to hear that music today anyway.

[1:29:24]

          Posttest 3: Rationale

So I think once again, most of you have gone with C having that open discussion to learn which needs are not being addressed by the current regimen. But also I think it is remembering that actually virological efficacy is the prime importance, but it's then working beneath that to see what else can you do to try and modify things and make things better for that individual in front of you.

So what I'm going to do with that, as I am going to unfortunately not have questions and answers. We did have some on the Slido, which people did answer. Actually, I think I'm going to give the final comment to Sophie's comment, which was awesome position Sophie about the positive empowerment for sex.

Yes, we do need positive conversations and sexual pleasure at the centers, and I think that is for anybody who is looking for PrEP or who is also going to be someone coming to your clinic and receiving ART on a long-term basis.