HIV Update: CCO Independent Conference Coverage of IDWeek and EACS 2025

Dr Joseph Eron (University of North Carolina): Hi everyone. Thanks for joining us. It's a pleasure to be here and fun to talk about this conference. I was at EACS in - in Paris, and Paris was great, and - and the conference was actually excellent.

[00:06:03]

Real-world Study of Salvage Lenacapavir + OBR in Heavily Treatment–Experienced People Living With HIV

So this first study is a real-world study of salvage lenacapavir plus optimized background. This is in heavily treatment-experienced people and from a group in Chicago—5 clinics in Chicago and 1 in Pittsburgh. They all were heavily treated. And this experience was for over 5 years from November 2020 to June 2025. And you can see the mean time since HIV diagnosis, 24 years. And about a little bit more than half had viremia, an RNA greater than 200, and a few, 6%, had very high viral loads. And the median CD4 count was 270.

You can see that there was a lot of experience and a lot of resistance. A few had actually resistance to all 4 classes of medications. And I just want to move you to the bottom of this slide. Despite that, it looks like 97% of people had at least 1 active agent in the optimized background. So that's going to be good for the outcome, I think.

So let's see what they found.

[00:07:27]

Real-world Study of LEN: Results

So first of all, 70 individuals started LEN. 38 of them were not suppressed. Of those, 31% stayed suppressed over a year of follow up. So 82% of those who were viremic were suppressed after a year of follow-up. Two are unknown. And then the remaining 5 actually had viremia. Most of the participants continued on lenacapavir, 62 out of 70. And the median number of days on LEN is basically a year's time.

I think the injection site reactions, there wasn't a lot of active reporting. We know that people who get lenacapavir get nodules. They should get nodules, actually, but there were - I think the main thing is that only 19 out of 70 required a clinic visit to look at their nodule. But if you think about it, that's actually relatively high.

INSTIs were the most common part of the optimized background. There were no virologic failures in those who were suppressed. The daily pill burden decreased, while the number of active agents increased. So that's a big advantage of - of lenacapavir. And in my practice, I've used it to replace boosted PIs in several patients.

And there are some limitations. This is observational. It's retrospective. The follow-up was not complete. And obviously there are a lot of different decisions for why people started lenacapavir. But in general, in these clinics, it functioned quite well.

[00:09:22]

Switch Studies in People Living With Virologically Suppressed HIV

There were some switch studies in people who were virologically suppressed. The EMPOWER study was a relatively small study. These were people who were on CAB/rilpivirine, but did not want to be on CAB/rilpivirine anymore. They were choosing to go off CAB/rilpivirine. They were suppressed.

The primary reason is they weren't tolerating the adverse effects of CAB/rilpivirine. And this study was designed to see, well, what happened to these people when they switched? Most people who switched off to B/F/TAF didn't experience any adverse effects. And then the vast majority of the participants reported considerable improvement in treatment satisfaction.

And basically, that's not surprising, right? Because they asked to go off CAB/rilpivirine. But I think what it tells us as clinicians is that for people who are suppressed on CAB/rilpivirine who want to go off for whatever reason, then switching them off to B/F/TAF is a very reasonable approach.

And then the PREFER-LA was another study of switching from oral therapy to CAB/rilpivirine. This is in 160 people - 159 people. Again, their concern was that they had suboptimal adherence. And of the people who switched, the vast majority, 97.5% preferred to be on the injectable, and 98% of those who switched, achieved or maintained viral suppression to less than 200, and 89% were suppressed at baseline. So that means 11% of participants were, and most of those suppressed.

So again, if you can get off CAB/rilpivirine. If you need to and go to B/F/TAF. But for many people, B/F/TAF, the CAB/rilpivirine seems to be the—a very active and—a regimen that people prefer.

[00:11:42]

Weight and Metabolic Outcomes in People Living With Virologically Suppressed HIV

Okay. So then the last bit of this section is looking at weight and metabolic outcomes. One issue, of course, is that people living with HIV gain weight when they start therapy. We can talk forever about what causes that. But these studies are - have to do with, if you change therapy, what happens? Right.

So there was a switch study from B/F/TAF to a new combination that's not yet approved, doravirine/islatravir. And so they went off an integrase inhibitor and TAF and they went to an NNRTI and an NRTTI. So no TAF, no integrase. And there was essentially no change in body weight. So switching off is probably not going to help.

The DO-IT study, which was done by the ACTG, kind of a study design to test that same question does switching off an integrase inhibitor and TAF to doravirine, either with TAF or with TDF in combination? What does that do? It's already been presented that there was no substantial change in weight. In fact, both groups kind of lost weight a little bit.

But the other idea was, well, maybe this will improve triglycerides or cholesterol or insulin resistance or total body fat. And switching did not lead to any of those changes. So no change in cholesterol, insulin resistance or body fat.

And then finally, the PASO-DOBLE study. This is an interesting study. It's actually been published, the 48 week in Lancet HIV. These were people that were on a non-integrase non-TAF-based regimen. So cobicistat-boosted, efavirenz or TDF-based. And they were switched in a randomized way to either B/F/TAF or DTG/3TC. So it was a direct comparison randomized B/F/TAF vs DTG/3TC. And at both 48 and 96 weeks, there was greater weight gain in participants that received bictegravir/TAF/FTC.

Now the difference was small. It was a kg or a little bit more, but more people shifted into a higher weight class. It was a difference and it was statistically significant, but it was small. Aadia, I don't know if you have any thoughts on any of this.

Dr Aadia Rana (University of Alabama-Birmingham): You know, it’s interesting. I mean, this is I think, beyond, you know, viral suppression. But probably the most challenging thing we deal with in clinics is this weight gain and maneuverability of ART is the 1 thing we can do. So I think we keep trying to do it to see if it makes a change. And frustratingly, it doesn't, or it so far has not shown.

I was curious with PASO-DOBLE because in the sense of—in this presentation, now it's Week 96. So we know that the impact of weight gain in initiation of ART, we see usually within the first year, and then afterwards it's hard to reverse the advances that we've made in that setting.

So now I was thinking, well, in all conditions, once you gain weight, it's hard to lose or it's hard to make changes. Maybe we just need a longer duration. And PASO-DOBLE unfortunately didn't quite show that. But I think what it did affirm is there is something about the integrase inhibitors. There is potentially something about TDF or TAF, or in this case, TAF, that we did see in some of the initiation studies where we saw the integrase vs other classes, particularly when paired with TAF vs TDF.

So how that directs us to make changes in ART is a whole different question. But I think, certainly, can potentially inform additional treatment initiation strategies that we need to test in this way.

Dr Eron: Great. Thanks.

[00:15:51]

          Posttest 1     

So I think now we have our first post-test question. So in a patient living with virologically suppressed HIV and obesity asked whether switching from their N - their integrase-based ART to doravirine regimen will help decrease triglycerides, LDL cholesterol - triglycerides, LDL cholesterol, and insulin resistance. You can counsel this patient that switching to doravirine is likely to…

1. Significantly decrease triglycerides, LDL, and insulin resistance;
2. Significantly decreased triglycerides and LDL, but not insulin resistance;
3. Significantly decreased insulin resistance, but not triglycerides or LDL; or
4. Have no significant effect on triglycerides, LDL, or insulin resistance.

So go ahead and vote. All right. Let's see what they said. So 83% of you - excellent - saw that there would - they would have no significant effect on triglycerides, LDL or insulin resistance.

[00:17:16]

          Posttest 1: Rationale

So if we look, that's the correct answer, D. And this is directly from the DO-IT study that - that did exactly that. There was no difference in weight change and no significant difference in these 3 areas. In fact, surprisingly, at least to me, insulin resistance went up going from integrase to doravirine. That was surprising to me. But there was definitely no decrease in any of these 3 metabolic measures.

All right. Turn it over to Aadia.

[00:17:54]

Phase IV CAPRI: LA CAB + RPV in People With Severe Renal Impairment and Virologically Suppressed HIV

Dr Rana: Great. Thank you so much. So I'll start off with some of the presentations from IDWeek. So I think in addition to the metabolic complications that we see or manage in our clinic, consequently, we also see a lot of renal complications. And there's been a lot of questions on the use of the long-acting agents, cabotegravir and rilpivirine in this population.

So at IDWeek, we had a presentation, a phase IV study, CAPRI, looking at long-acting CAB/rilpivirine in people with severe renal impairment, and this included people on hemodialysis. But were people who were virologically suppressed so that it was in that component.

So this was a small study because they were doing detailed PK/PD studies of 12 adults. And again, half of them were on hemodialysis. And they found, you know, excellent efficacy in terms of virologic suppression and CD4 cell count also maintained. I think notably there were 2 patients in this or participants in this study who did receive renal transplants. And even for them, they stayed on the long-acting agents. There were no issues with drug-drug interactions and were able to continue even after their transplant.

And there, the kidney function was stable and increased in—sorry, it was in 3 patients who received the transplant. No significant adverse reactions were noted, with the most common reaction being injection site reaction, not surprising. There was 1 death reported due - due to a non-ST elevation MI, but not associated with long-acting CAB and rilpivirine.

So I think for those of us managing these patients in the clinic, certainly, this study helps provide data on its use in this population.

[00:19:57]

MORE: Mobile Delivery of LA CAB + RPV to People Living With HIV and Adherence Challenges

I think with the use of the long-acting agents, certainly a lot of interest on its administration outside of the clinic and particularly in those with challenges with adherence. So this study, the MORE study, mobile delivery of long-acting CAB and rilpivirine to people with living with HIV and adherence challenges.

Part of this data was presented earlier this year at CROI, and this is from the Whitman-Walker Health clinic in DC. And so, in their study design, they had presented initially enrolling a cohort of about 60 people who had challenges with adherence and matched them with those who were in clinic and receiving long-acting to see if there are any differences in outcome.

And there was an improvement in viral suppression, of course, in that population, that was receiving, or chose to receive injectable through this program compared—and similarly high levels to the control in the clinic.

So what we're looking at here is looking at the implementation outcome. So specifically those looking at agreement of this intervention of in terms of acceptability, feasibility and appropriateness of home-based delivery of long-acting injectables.

And so what they presented was actually pretty high rates of acceptability and feasibility, inappropriateness with 67% willing to receive home injections. And of the population that they surveyed, about a third had received at least 1 of these home injections. So I think as a potential strategy, part of the strategy to offer or increase access to these agents and particularly those who have challenges with adherence, I think this study provides some of that data on building a program at your site as well.

[00:22:17]

Low Risk of HBV Reactivation After Nucleos(t)ide Withdrawal

And then I think another question that comes up on the use of long-acting is the consideration for a hepatitis B reactivation. And so certainly guidelines currently suggest that everybody be tested before the initiation of long-acting CAB and rilpivirine to check their hepatitis B status, certainly vaccinate if indicated.

But these 2 cohort studies, 1 in Barcelona and the other, the Swiss HIV Cohort Study, looked at individuals who had been initiated on long-acting and then retrospectively looked back to see HPV status and sort of the outcome.

And so from the Barcelona study, they had participants who they identified, who were hepatitis B surface antigen negative, but also core antibody positive, so evidence of exposure in the past. And among those there was no hep B reactivation. Of note, not on the screen, but there were 4 participants who were—4 in the cohort who were actually inadvertently started on long-acting, who were surface antigen positive.

And of those 4, 2 of them did have reactivation or evidence of DNA viremia, within 6 months of initiation on long-acting, were able to switch back to a tenofovir-containing regimen, and then suppress. The other 2 actually did not, but were found to have the surface antigen positivity and then were returned back.

Similarly, in the Swiss Cohort Study, there was HPV DNA positivity in 1.1% of those who were switched, vs 5.6% to a non-HPV active ART. Overall, HPV DNA or hepatitis surface antigen was positive in almost 4% of all people 1 year after switching from tenofovir.

We will note that almost 80% of the people in this cohort were surface antibody positive. So sort of the ability to really see, you know, when we consider really large rollout of long-acting CAB in populations that have more hepatitis B endemicity, still something to consider.

[00:24:58]

Investigational ART Regimens

I think now I'll turn it back over to Joe to talk about investigational ART regimens.

Dr Eron: Great. Thanks, Aadia. Very, very thoughtful. Okay. So investigational therapy.

[00:25:15]

EMBRACE: Every 4 Month IV or SC N6LS + Monthly CAB

So not surprisingly, investigational therapy now is very much focused on longer acting alternatives. So this is the EMBRACE study. This is a study looking at every 4 month intravenous or subcutaneous administration of a bNAb, a long-acting, broadly neutralizing antibody called N6. So this is N6LS. So it's got the mutations that make it long-acting. It can be given every 4 months.

And this is a study where this N6 antibody was partnered with monthly cabotegravir. So this was a multicenter randomized trial of people suppressed on oral therapy. They couldn't have hepatitis B. They had to have a CD4 greater than 350. And their virus had to be sensitive to this long-acting antibody.

And they were randomized to either IV N6 plus CAB. Remember CAB is monthly, M6 is—N6 is every 4 months. Subcutaneous N6. And in order to make it work subcutaneously, they actually get a hyaluronidase additive that actually essentially makes some space for that subcutaneous antibody. They got CAB. And then a group was randomized to stay on their oral therapy and it was 2 to 2 to 1 randomization. So twice as many people got the CAB and long-acting in each of the arms.

They did have actually shown the outcome results at CROI. And the outcome results showed that people that stayed on their therapy, oral therapy stayed suppressed. And they did note that there were more individuals on the SC arm that actually had viremia on this regimen.

[00:27:30]

EMBRACE: Safety and Tolerability

So the presentation was about safety and tolerability. And I think the real message here is that the IV formulation of N6 was very well tolerated. There were no serious treatment adverse events, no discontinuations, no injection site or infusion site reactions, no immune events and no lab abnormalities with the IV or with the SC.

However, the SC actually had more adverse events, and not surprisingly, because of more adverse events and more virologic rebounds, they're not going forward with the - with the SC. Though in general, the participants rated IV and SC as highly tolerable.

So based on this, these data, there's a part 2 of the EMBRACE study which is going to evaluate twice yearly IV N6LS. So twice yearly broadly neutralizing antibody plus long-acting cabotegravir every 2 months. So really getting even more long-acting than the initial study.

[00:28:53]

Twice-Yearly Lenacapavir + Teropavimab + Zinlirvimab: Study Design

A another long-acting combination is this twice-yearly combination of lenacapavir, which, you know, is a subcutaneous injection, teropavimab, which is another long-acting neutralizing antibody, and zinlirvimab, the another long-acting neutralizing antibody.

This was also a phase II. It was a randomized, open-label, multicenter trial where participants were randomized to receive either this 6 monthly combination of an injection and infusion or continue on their stable oral therapy through 52 weeks. And this is actually the first presentation of the 52-week data.

The primary endpoint was the proportion of people greater than 50 copies at Week 26. That was also presented at CROI. But now I'll show you the week 52 data. And then secondary outcomes included proportion less than 50 and also safety and CD4 change.

[00:30:06]

Twice-Yearly LEN + TAB + ZAB: Wk 52 Outcomes

And what you'll see is that there were 3 individuals that had this very tight definition of virologic rebound on the long-acting arm, while there were no rebounds on the stable oral ART arm. There were a few missing data in the window. But those people will be followed.

Of the 3 people who had virologic rebound, there was 1 case of resistance to lenacapavir, 1 case of resistance to zinlirvimab, actually, that person had also lenacapavir resistance. And then the third person, interestingly, had low level viremia that was persistent and there was no resistance.

All 3 resuppressed on oral B/F/TAF. But the person with the low level viremia actually took 20 weeks to suppressed on B/F/TAF. So that may not have been a virologic failure.

The most common adverse event was the subcutaneous nodules related to lenacapavir. CD4 cell counts increased, and most of the people preferred the long-acting therapy. Obviously it's not for everybody, even everybody who signs up for a study. But it is an every 6 monthly therapy that appears to be effective and I would say easily rescued, with oral therapy because you don't end up with resistance to an integrase inhibitor, for example.

[00:31:43]

Once-Weekly ISL + LEN: Study Design

And then finally, the last long-acting study. This is long-acting with weekly dosing of islatravir and lenacapavir. Islatravir people might remember, is kind of like an NRTI, but it's an NRTTI. It does 2 things when it blocks reverse transcription. So it's actually incredibly potent molecule. You can take, in this study, 2 mg once a week.

So this was a phase II study that was initially randomized to either islatravir-lenacapavir or to B/F/TAF in people who are suppressed. And what I'm going to show you now is the 96-week data. So this is 96-week data on once-weekly therapy.

We don't have data from the control arm yet, but this is just a group that received 96 weeks of once-weekly therapy.

[00:32:41]

Once-Weekly ISL + LEN: Wk 96 Outcomes

There were no virologic rebounds greater than 50, zero, none. Everyone who was available at week 96 were suppressed. There were 6 people who weren't. Those 6 discontinued for a variety of reasons, but none were related to the study.

Obviously, there was no emergence of resistance. And the mean adherence was 99.3%, so people could take a pill once a week. There were some adverse events, some dry mouth and some nausea and then a whole bunch of others that didn't occur in more than 2 participants. There were no serious adverse events related to study drug or resulted in discontinuation. And there was no significant decline in CD4 lymphocyte counts through Week 108. There was some downtrend at week 96.

But when the CD4 and lymphocyte count were repeated in Week 108, that trend that was apparent was not sustained.

And there are 2 ongoing phase III studies of this combination, ISLEND-1 and ISLEND-2 that are I think now are both fully enrolled. So this is actually a therapy that could be coming to us, maybe in 2026, but probably early 2027, if all goes well.

[00:34:17]

          Posttest 2

All right. Here's your second question. In the extension phase of - of a phase II trial, evaluating once-weekly islatravir and lenacapavir for people living with virologically suppressed HIV. What happened?

1. No one had HIV RNA greater than 50 copies per ml at discontinuation;
2. Several people discontinued because of a CD4 decline;
3. Several people discontinued because of treatment-related adverse events; or
4. Many people forgot to take their once-weekly islatravir-lenacapavir.

So go ahead and vote. I'm also going to say you can put questions in the chat. It's - in the question and answer thing. It's okay. If you have a question type it in there. We'll - I - we'll probably have time to answer a few. So go right ahead.

Alright. Let's see. Alright, people are listening. Excellent. No one who had HIV RNA greater than 50. Anybody who discontinued was less than 50. And everybody at the end of 96 weeks was less than 50. So that's - that's what we saw. Thank you for paying careful attention that - that you're right on target.

[00:35:40]

Key Takeaways: Treatment

Okay. Key takeaways from treatment. Treatment satisfaction is high after switching ART. No weight change and metabolic parameters after switching to a doravirine-based regimen. But in a study, there was less weight gain with DTG/3TC vs B/F/TAF. There was low HPV reactivation when switching ART either to a regimen with no hep B activity or people on only 3TC or FTC.

Mobile delivery of CAB/rilpivirine was feasible and acceptable. Long-acting CAB/rilpivirine is effective and safe in those with severe renal impairment. That's important for a small number of people. And then we saw that N6 plus CAB twice yearly, LEN, TAB and ZAB, and weekly oral islatravir-lenacapavir all appear to be tolerable and are moving along in the path towards a phase III studies or are in phase III studies like islatravir-lenacapavir.

So back to Aadia.

[00:36:55]

HIV Prevention Strategies

Dr Rana: Thanks, Joe. It's a great review. Quick review of all of the exciting drugs hopefully coming our way in the treatment pipeline. Alright, so we'll now switch over I think to some HIV prevention strategies.

[00:37:13]

PURPOSE 2 Persistence Subanalysis: Annual Persistence to Twice-Yearly SC LEN vs Daily Oral FTC/TDF as PrEP

And so this is a study doing a subanalysis of PURPOSE 2. So as a reminder, PURPOSE 2 was the international, double blind, randomized phase III trial, focused on over 3000 cisgender men, transgender women, transgender men and gender non-binary people is 16 years and older.

And as you all are probably familiar with from this PURPOSE 2, the HIV incidence from twice yearly SC LEN was significantly lower vs the background HIV incidence or even compared to a daily oral FTC/TDF.

And what this study wanted to do was look at the annual persistence. So people staying on these agents, comparing both LEN and oral FTC/TDF as PrEP. And so this study looked at that and - and preselected about 10% of people who had more than 1 year of follow up at the primary analysis.

[00:38:23]

PURPOSE 2 Persistence Subanalysis: Annual Persistence to PrEP

And I think, not surprisingly, you found higher annual persistence to twice-yearly SC injection vs a daily oral pill with FTC and TDF. And so about 63% of the people continue to be persistent with lenacapavir vs just a little over a third on oral FTC/TDF. And they defined LEN persistence as getting the baseline injection, getting an on-time injection at least about 28 weeks after up at week 26. And then - and then on-time follow up at week 52.

So they still had to come in and - and have all of this done. And so overall adherence to LEN and the placebo injections was over 90%. And you did have initial high oral adherence to PrEP, but quickly waned from 82% at week 8% to 62% by week 52. Still fairly high, I think. But of course, in the context of a clinical trial, but certainly significantly higher annual persistence of twice-yearly LEN vs the oral.

There was still nonpersistence even in this setting in 36 of the 98 people receiving LEN and 32 of the 51 receiving FTC/TDF and LEN. Twenty-one missed their Week 26 injection, 14 had missed on-time injection, so a delayed injection and 1 had a late week 26 injection.

Whereas with FTC/TDF, you also had 18 people missing at least 1 dried blood spot sample to check their adherence and 14 had more than 1 DBS, dried blood spot concentration indicative of nonadherence in the prior 8-12 weeks. So again, I think findings that are not so surprising.

[00:40:34]

PURPOSE 2 Subanalysis: LEN PrEP Adherence and Safety Among People Who Used Substances

The second subanalysis that was presented actually looked again same population of PURPOSE 2 but wanting to look at any differences in outcomes based on substance use. And so they were able to actually define substance use as either binge drinking, any drug use, stimulant use, opioid use, or injection drug use.

And as you can see on the table there, binge drinking was the highest, about 40%, 37% reported any drug use and about 20% reported stimulant use. We didn't see very high numbers of reported opioid use and less than 1% injection drug use. But the findings were that the adherence was similar between those who used substances and those who did not, and again, with the definition of the on-time injections less than or equal to 28 weeks from the last injection.

And we didn't really see any difference in adverse events across any of the substance use categories. Although again, the number of those in the injection and opioid use categories was relatively low.

In addition to injection site reactions, the most common adverse events included chlamydial, gonococcal, and upper respiratory infections, and they have preliminary pharmacokinetic modeling, suggesting really no significant lenacapavir, fentanyl interaction. So something for us to consider.

PURPOSE 4, which is currently enrolling or should be hopefully fully enrolled soon, is specifically looking at the use of lenacapavir in those with substance use, and based in the US. And hopefully we'll have some data on those outcomes and more detail in the coming year.

[00:42:42]

PURPOSE 2 Gender-Affirming Subanalysis: LEN PrEP Coadministration With Gender-Affirming Therapy

Another subanalysis for PURPOSE 2 looked at the co-administration of LEN with gender-affirming therapy. And so they had over 2000 participants with 11.6% receiving some type of gender-affirming therapy, usually, you know, either estradiol or testosterone. And there was no significant impact of lenacapavir on concentrations of those agents generally remaining comparable between baseline and when they were on lenacapavir.

[00:43:22]

CLARITY: Cabotegravir vs Lenacapavir PrEP

And so then the CLARITY study was looking at—basically at, you know, tolerance of cabotegravir vs lenacapavir as PrEP. So this was an open-label, randomized, crossover study in people without HIV, obviously for PrEP. And so folks were randomized to receive either or, and then could also—there was an acute observation phase. And then they received their, you know, respective therapies and then, you know, crossed over and received the other one as well.

And the primary endpoint was just the participant-assessed local reaction accessibility, 7 days post injection, using a 21 item questionnaire. And they were looking also specifically secondarily at injection site reaction incidence, severity and duration, and then preference as well.

[00:44:27]

CLARITY: Local Reaction Acceptability and Preferences

And so what they found here was that LEN was associated with more frequent and visible, injection site reactions vs CAB, cabotegravir. So not surprising. Lenacapavir is SC and forms a nodule and cabotegravir is intramuscular injection. And so non-pain injection site reactions were evident in 100% of lenacapavir vs half of CAB. And grade 2 higher injection-site reactions 57% with lenacapavir vs 30% in cabotegravir.

So overall cabotegravir was associated with lower initial pain scores vs LEN. But then as sort of the, you know, days continued, they were similar on Days 3, 5, and 8 with peak pain at Day 2 roughly of cabotegravir vs Day 3 of LEN.

And 6 of 7 healthcare providers surveyed preferred CAB to LEN due to reports of fewer and less severe adverse events and less pain during injection. And you can see on the graph here that in terms of participant preference at Day 22, you had 54 out of 60 preferring CAB and 6 out of 60 preferring LEN and then comments as well about the local reaction rate rated as totally or very acceptable 69% for CAB vs 48% for LEN.

[00:46:06]

Key Takeaways: Prevention

So our key takeaways for prevention. So PURPOSE 2, we did have a higher annual persistence with twice-yearly LEN PrEP vs daily or oral PrEP. There was similar adherence and safety in people who did or did not use substances. But again, we'll have more detailed data for that on substance use and lenacapavir in PURPOSE 4 and no interaction between LEN and gender-affirming hormones.

And in this small study, the CLARITY study, there were local reactions rated as totally or very acceptable by 69% of those receiving CAB vs about half of those receiving LEN. There were more frequent and visible injection site reactions with lenacapavir vs cabotegravir. And 6 of 7 HCPs preferred CAB and LEN due to fewer adverse events and reduced pain.

[00:47:04]

          Posttest 2

So I think we'll go to our final post-test 3. So the question is now I am familiar with data from the EACS 2025 and IDWeek 2025 conferences, and I plan to translate these data into current or future management strategies.

1. Strongly disagree;
2. Disagree;
3. Neither agree nor disagree;
4. Agree; or
5. Strongly agree.

And I'll give you some few moments to answer that question.

Dr Eron: So after you - after you answer, feel free to throw a question or 2 in the question and answer box. I have a couple questions for Aadia. So.

Dr Rana: Okay, let's see how y'all feel.

Dr Eron: Oh, excellent.

Dr Rana: Much better. It's great.

[00:48:11]

Q&A

Dr Eron: Super. There is a question in the question and answer box. This is actually a very important question. A person who wants to go off CAB/rilpivirine either because of insurance issue or side effects. How long should we wait before we start the oral regimen? And - and I think the guidance now is you really don't have to wait. The - obviously they'll have cabotegravir and rilpivirine in their blood, but if you - if you choose B/F/TAF or DTG/3TC, obviously there's no NNRTI so that's not an issue.

And - and the - even the cumulative concentrations of bictegravir and cabotegravir or dolutegravir and cabotegravir don't pose a risk. So if someone needs to go off, you can start their oral therapy. So that - that's fine.

Aadia, in - in your - at UAB, do you guys have an algorithm or a - a Epic dot phrase for - for people who are switching off of an oral therapy that contains tenofovir to CAB/rilpivirine in terms of what H - HBV testing that you do? And then I have a question about, when you get those results, what - what do you do depending on the result?

Dr Rana: So, yeah, I think it's - that's a great question. And I will say, first off, we do not have an Epic dot phrase because we do not have Epic yet. That is going to be - that is a transformation in 2027 for UAB. So stay tuned. That's a great idea. We should certainly do that. So no, we're currently in a - in an older EMR. And - and we don't. And that is right now, we - for everyone who is switching to CAB/rilpivirine, there is a nursing staff that review - you know, reviews and checks hep B status and makes recommendations for, you know, like vaccination if needed.

Separately for those with adherence or, you know, viremia, we have actually a team of people who review those, so similarly in that setting. We have come across folks who are - as has been - was described in the Swiss Cohort Study and the Barcelona study, hep C antibody positive but surface antigen negative. And is it safe? Can we give it to them?

And I think what we have actually shown - recommended is just close monitoring after initiation up to a year. But I think a lot of this data shows us, you know, maybe - in that particular population, we may not necessarily need to do that close monitoring. I mean, we're probably overdoing it with fairly regular checks. But yeah, I think it's a - it's an interesting question as to how - I mean, well, revaccination for hep B is also another…

Dr Eron: Sure. Yeah, no, for sure.

Dr Rana: For us to consider, but I don't know how - how are you guys doing?

Dr Eron: Yeah. No, we - we don't - we - we - we should have a very specific order set or - because I do think if someone hasn't had hepatitis B surface antibody test in the last year or 2, they should get a surface antibody test. Even if you knew in the past they were -

Dr Rana: Sure.

Dr Eron: They were surface antibody positive. That's a bit of a change in dynamic, right? That - that we say once you're positive, forget about you. But I think if you have long-standing HIV, it's worth retesting people when you switch. And so we're implementing that. We have had people sneak through that that were, in fact, not antibody positive and were antigen but not DNA positive. So that - just like in that Barcelona group that you were talking about.

That the 1 group I think where we have equipoise about or not equipoise but - but nobody's exactly sure. If someone's just core antibody positive but they're surface antigen negative and antibody negative, should you vaccinate that person?

Dr Rana: Yeah.

Dr Eron: Right? I personally think there's almost no harm in vaccinating them, so I would do it. But whether that's the right thing to do? I have no idea. And…

Dr Rana: I'll add - I'll add another element to that. What if they're viremic? Should you vaccinate them first before you start CAB/rilpivirine? Or should you wait for their viremia to be controlled?

Dr Eron: Yeah. Yeah. No, I don't know the answer to that. I - my - I would probably wait till they - their viral load went down because we know viremia is - is immune suppressive. So there is a question. We engendered a question. For hepatitis vax - back - B vaccine to use Heplisav as first-line or Engerix? That's a no brainer.

That is Heplisav, 100%. The ACTG did a wonderful study, published now several times the primary results. And for sure whether they're someone who is vaccinated in the past and needs - didn't respond, they should get Heplisav. And if they're never been vaccinated and they're HIV positive, they should get Heplisav. I think that's - that's very clear and it's quite, quite effective. Great.

Dr Rana: So I have a question for you, Joe.

Dr Eron: Okay.

Dr Rana: Of the studies in these investigational drugs, I mean, we are definitely chasing the interval, the duration interval, right? And the dream is - I mean, well, honestly, the dream would be cure for sure.

Dr Eron: Sure.

Dr Rana: That's that. But in terms of needing treatment, an interval of Q6 months is right now I think the aspirational like, can we get there. And of these agents combination where - who do you think - where do you think we're the closest.

Dr Eron: Yeah, that's a really good question. I mean, honestly, I know where we're the closest whether - whether it's how useful will be and whether it'll even make it. So I think the - the lenacapavir and the 2 antibodies are by far the closest. I mean, there is actually discussion about the starting of phase III trial, right? And I think that the issue is, well, you have to have testing. Only about 50% of people will be sensitive to both antibodies. Who is that - is that useful? Right.

And maybe for some people, it'd be quite useful. And that's by far the closest. The CAB N6, it really won't be every 6 months for a while, because the longer acting CAB is going to take a while to get there. So that's - that's definitely farther down the future. They have to - they have to do the phase II first.

And - and then what we really want is - is lenacapavir and another small molecule, and there are long-acting integrase inhibitors that look like they might get out to every 6 months, but they're in like, you know, first in - in - in man type studies, right? Or at least first in HIV to show that they work. So - so you know what that means. That means 4 or 5 years from now.

So - so for - if - I - so the - the answer is easy. It's - it's LEN, TAB and ZAB if it works and if it goes forward. There's a lot of issues right about can they make the antibody? Is there enough? Would it be too expensive for anybody even to consider? Those are all - but that's the closest.

I do think - and this gets to the discussion we were having, you know, before everybody got on the call. You know, this, LEN/islatravir once a week and the idea that maybe once a week is enough for video-assisted dosing, right? So - so VOT, video observed therapy, or - or - or once weekly text messaging or whatever. That's maybe a little more…

Dr Rana: Or even a community health worker, right? It's a pill. So that theme...

Dr Eron: A little bit more practical. You know, you can't really do that with daily therapy. So I think that one I think - like I said, I think that's like a year and a half from now. If the phase II data bears out. I mean there's just nobody - nobody rebounded at all. There was no, like, blips like there are with these antibodies. There was nothing. Right? You know, so, that's my opinion.

Dr Rana: I agree. I agree. That's exciting. I mean, even better would be a monthly oral pill, I think, in a lot of sort of feasibility and pre-implementation studies when they survey patients potentially, they talk a lot about even Q6 month injection or once-yearly injection. They're preferring they, at least hypothetically, a monthly pill, you know, which is certainly, in that way. But I think weekly is still especially potentially in some critical and vulnerable populations a really - a really important.

Dr Eron: Yeah. Methadone clinics could do - you know, there's a lot of ways this could get done. And the other thing I would say, we do know that the monthly pill for PrEP that started - that study has just started.

Dr Rana: Yeah.

Dr Eron: And is actively enrolling. There just is no good partner. Now, I don't know whether these long-acting integrases, have like an oral form. I know they have an injectable form that has very long - very long half-life. I don't know if there's an oral form that that - so we'll see.

In - in the next year, we're going to see a lot of data on those longer acting integrases I think. So all right, well, I am going to jump. This is - Aadia, this is fun. It's great to listen to you. And thanks, everybody, for - for staying on the call and paying attention and - and be safe out there.

Dr Rana: Thanks, everyone. Good to see you all. Bye-bye.

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