HIV Update Podcast: Independent Conference Coverage of CROI 2026

Hello, and welcome to the DeSera Clinical Education Efectious Disease Podcast.

I'm your host, Dr. Karen Stravy West.

Today's episode features audio from a live conference coverage webinar, summarizing and

discussing the latest updates on HIV treatment and prevention from Chorey, 2026.

I'm joined by Dr. Monica Gandhi from San Francisco and Dr. Jean-Michel Molina from Paris

to view the full educational program and follow along with the slides.

Please visit the show notes for this episode.

No, let's get started.

Great. So we're going to start talking about the new HIV treatment that got presented at the

meeting, which were quite a bit this year and pretty exciting. So let's start with the

artistry one study. So, big tegravere, of course, is an in-steel and a capavir is a

capsidine inhibitor and there's been a lot of interest in putting an in-steel and a capsidine

inhibitor together as a pretty high barrier to resistant regimen. And what artistry one was

specifically is people who were on complex ART and got switched over to Big Lens and then what

happened up 48 weeks. Now, importantly, if you look at this phase two, three trial,

this was a population that was quite a bit older. So the median age was 60 years old,

77% were over 55. And also the mean duration of being on antiretroviral therapy prior to this

was 28 years. So really complex regimens. A lot of people were actually on two pills,

even three pills, four pills. You can see that there was BID or twice a day dosing, 41% of participants

were on twice a day dosing. So it was complex ART. But importantly, they were all suppressed.

Both artistry one and two and we talk about them are all suppressed individuals and then they

got switched over to Big Lens. One other point is that there was some preceding resistance and in

RTI resistance, these are again complex ART, been on ART for a long time. So a lot of at least

historical resistance of an RTI resistance and RTI resistance and just a little bit of

interesting resistance. So what are the results show us if you either stayed on your complex regimen

or got switched to that single pill of Big Lens. Well, there was actually non-inferiority of

Bictegravir and Lennacapivir compared to complex ART. And there were a few people, three participants

who had low level viremia, but they didn't need to switch on Big Lens. They re-suppressed on

Big Lens. And so essentially was a non-inferior regimen. And then importantly, there were no

city for cell count changes. Now, the question would be, was this better to be on Big Lens?

And there were a couple of outcomes that looked at, there were some improvements. What I mean by

that is that there was improvement in lipids when in the group that got switched to Big Lens

versus staying on their complex ART. Now remember, complex ART is most likely or there was a lot

of boosted PIs. And so probably it was the boosted PIs more increase in triglycerides, total

cholesterol, LDL, and switching over to Big Lens improved those three cholesterol parameters.

And then also if you asked participants in patient reported outcomes, if you liked the

Bictegravir, Lennacapivir, a lot of people, of course, in this makes sense, would like that single

pill combination instead of their complex regimens that were sometimes twice a day and lots of PIs,

and it was just harder to take. So of course, the patient satisfaction was improved with one pill

once a day. So what did artistry one show us? There was really good question announcer, like the

thing about Kroy and the thing about any meeting is listening to the question answer. And you know,

question that was posed was why not switched to Bictalfel FTC? And wouldn't that have been just as

okay as Big Lens? And I think it was important to say that there was a certain amount of NRTI resistance,

as I said, 66% NRTI resistance, even though you can use Bictalf FTC with an M84V,

and when you use it with lots of NRTI resistance, because that's just going to set you up for

a BIC resistance. And then there was a little bit of entity resistance, about 4%, and I wouldn't

want to use Bictalf FTC with that either, and Lennicapivir has a high genetic barrier resistance.

So this was the main study that really looked at Biclen compared to complex ART. Now the second

BIC study that was presented at Kroy with Bictegrivere and Lennicapivir was the artistry two study.

And in this case, it's the same drug company. So it's actually switching from Bictalf FTC

over to that single pill combination of Biclen. Now these are going to be younger patients and

not as much long experience being on Bictalf FTC, because that only came out in 2018. And there was

though a certain amount of comorbidities in the population, as you can see here, dyslipidemia,

hypertension. And then the question was, was there equal efficacy non-inferior result when you

switched over to Biclen? And so the artistry two data showed us that the outcomes of 48 weeks

is that Biclen looked pretty much equivalent non-inferior to staying on Bicalf FTC. So it was

non-inferior at 48 weeks. Now, importantly, and I think this is important to say, there is no

drug in the world that has an impenetrable barrier to resistance. So there was one person in the

Biclen arm who had Viremia and essentially developed an R263K. This person importantly had had

Dolategrivere and Laltegrivere experience in the past. But the fact that there was an isolated

R263K, and the Mexico City data shows that R263K is probably the signature mutation of Bictegrivere,

even though it was phenotypically sensitive, I absolutely would not use Bictegrivere with an R263K,

especially one that emerged. So just like you're going to see in these Lativer Dravering trials,

later there was one person in Lativer Dravering too, but there was emergence of one resistance

mutation. So nothing is impenetrable. But in general, Biclen looked very good compared to both

complex ART and Bictef FTC, and the combination of the data from artistry one and artistry two is

going to enable the drug company to file for Bictegrivere lena capiver as a single pill combination.

It's going to be pretty small. The Bictegrivere dose is 75 milligrams. The lena capiver dose,

it's 50 milligrams. It's going to be a pretty small pill, and essentially this is going to be a drug

that we can use one pill once a day, and we'll see if we switch people to that for complex ART.

It's really a Tenofevere sparing regimen, which when we go into the next phase is kind of the theme

of the day of both these drugs, Biclen and Dravering is Lativer sparing of Tenofevere. So I'll turn it

over to Dr. Molina for the next part. Thank you very much, MoneyPump. And indeed, that was a great

conference. We've seen a lot of new data, and this trial, Dravering is Lativer here versus Bictef,

was one of the naive study that attracted a lot of interest, because that's the first time

these two drug combinations of Dravering is Lativer here was tested against the standard of care,

the combination of Bicteg, where the FTC and TAF. And this was a double blind, randomized

placebo control study. It was a known inferiority study. What it is interesting is to look at the

inclusion criteria. So people had to be anti-ritual vinyl naive at the very low to both 500 copies per

amount, and no non-resistance to Dravering or NETIs, or no active HPV infection. That's important

to keep in mind, because you're treating here naive patients. So it was clear that people

either have to have resistance to Dravering or NETIs. And so the participants were randomized,

one to one, to a combination of Dravering is Lativer here, but with the lower dose of is Lativer

here as compared to the one was used in previous trials, which was associated with the decline

lymphocytes. Here we use the dose of 0.25 mg of is Lativer here instead of 0.75 mg in previous studies,

with the RADRIN 100 mg in a single pill versus Bicteg and the usual dose. And the primary endpoint

was at week 48, the proportion of patients with a Valorado Bila 50 copies per ml, with a non-inferior

t-mogin of 10%. We also looked at secondary endpoint in terms of Valorado Bila 48 copies per

ml, and also the change in the city for sal count, and body weight to see whether these two

drug regimen would be associated with a lower increase in body weight as compared to big F-tath.

So at baseline, the patients were pretty young. Remember that Bicte is a naive study, and you can

see that the enrollment was really worldwide with people in Latin America, North America,

Africa, Europe, and Asia. Now there was quite a significant proportion of people from

where it's panicked. Only 24-25% of women, the median city for was quite high, but still 20-40%

of the population had less than 240 cells. And when you look at the median HIV RNA,

it was in the range of 50,000 copies per ml, but you can see that nearly 35% of the population

had the Valorado Bila 100,000 copies per ml, which is interesting to look at. In terms of HIV

subtypes, most participants had the HIV subtype B, and you know, when you look at people who had

anti-HBS and HBC antibodies, negative that was nearly half of the participants.

Regarding the primary endpoint, which was the proportion of people with plus my HIV RNA below 50

copies per ml, we are here at week 48, and you could see a pretty high proportion in both arms,

91.8% with the revenue slap review, and 19.6% with BFTAF. So the treatment difference is 1.2,

and when you look at the lower bone of the conference interval, you can see that it is greater than

10%, so you can clearly claim no infeurity of the revenue slap review versus the standard care.

Also, it's not going to be shown on this slide, but there was a similar increase

in a C4SAR account in both study arms. What you could see here also is the few participants

were Valorado, both 50 copies per ml, 6 with a revenue slap review, and 9 with BFTAF.

And what it is interesting here is to look at the resistant data, and for BFTAF, there was no

resistant mutation that emerged, and whether in those were available 50, only six of them in the

revenue slap review arm, we'll see that two of them had resistant mutation emerging, and this

is going to be shown on the next slide. So we're going to look in detail at those two

individual, so you can see that this individual had pretty low C4SAR account at baseline, 31,

and 171. They also had a very high revenue at baseline, more than a million copies per ml.

At baseline, the genotype was really susceptible, and you could see that at the time of

discontinuation, the Valorado was also quite high, and you can see the resistant mutation emerging,

so in the first participant, M184i, and Y188l, and in the second participant, the L74i,

the V1068, M14V, and F227l. And so these mutations are well known mutation associated

with deraverine resistance, and you could see when you look at the phenotypic susceptibility

that there was a significant increase in deraverine susceptibility, so these isolates were really

resistance to deraverine, and there was also an increase in the slap review phenotypic susceptibility

by two to six four. So these are rare events, but they still occur. In terms of serious adverse

events, we had two serious adverse events that were treatment related in the deraverine

slide will be on. There was one breast syndrome, and another participants were actually

developed, drug induced liver injury, and as I said, the increase in C2SAT count were similar

in both arms. What was a little bit disappointing was that the increase in body weight was similar

in both treatment arms, so there was no benefit in terms of body weight with the dual combination

of the slap review and deraverine. So let's look now at other data with the same combination,

but this time in people already on treatment, so these are switch studies. This first one is also

a randomized placebo control study comparing deraverine slot review to VF tab. So participants

in role in that study had a very large surprise below 50 copies per ml, LBF tab, with a total

lymphocyte count of both 650, just to make sure that we were saved in terms of potential decline

in lymphocyte, which actually did not occur. C2SAT count of both 50, no history of treatment failure,

and no deraverine resistant mutation, no active HBV infection. So here, the endpoint looked again

at the viral node. Resistance was only done when the viral node was confirmed, both 200 copies per ml,

and we looked at the viral RNA above 50 copies per ml, because we are looking at switch studies

on the endpoint is how many participants at the viral node that was above 50 copies per ml.

So let's look at the results.

And in terms of baseline characteristics of the participants here, where 15 years older than in

the naive study, so in the range of 48 to 47 years, still around 20 percent of women,

and you could see that the median times in shabby diagnosis was pretty long, 11 years,

10 to 11 years. And these participants were on BKFTA for a media of three years.

The C4SAT count at baseline was as expected quite high, nearly 700, and more than 90 percent of the

participants at the viral node above the C4SAT count above 350. So if we look now at the viral

node response, so at week 96, what you need to look at is in the middle, the participants who had

a viral node above 50, and you could see that the randomization was 2 to 1. So you had twice more

participants in the delivering this lateral view arm as compared to the BFTAF arm. So in terms of

proportion of participants with the viral node above 50, it was a very similar 1.5 percent,

there's just 1.2 percent, 5, there's just 2 individuals. And you could see that the treatment

difference and the confidence that it will can show you that there was no inferiority here in terms

of the measurements of the viral node below 50 copies per mile in those participants. As expected,

the vast majority of participants in both arms maintained the viral node below 50 copies and

also below 200 copies per mile. And there was no difference in the C4SAT count or in total of a

side count. And this was reassuring. Those data plus the data from the naves that you confirmed

that using these lower doors of the SLAP reveal 4.25 milligram, there was no impact on C4 or

2,000 for side count. And so these are quite reassuring data.

So in terms of safety, there was in that trial, no clinical HPV reactivation,

but still a few individuals had a low level varimia regarding HPV without antigenemia or

elevated transaminase. And there were also four cases of acute HPV infection, both with negative

HPC antibody and HBS antibodies at these lines. So these are a quite HPV infection because

neither the robbery nor SLAP reveal had any activity against HPV. This is quite different from

BFDF. As I said, no difference in body weight changes at week 96. And again here with more follow-up,

it's a bit disappointing to see no benefit each of the impact of body weight with this dual

combination of the reverim and SLAP reveal. So the next study that we want to present

is Latvier and Lennon Capavier. Okay, so let's remember what each of these drugs are. So

as Latvier, what we just talked about was looked at as a daily combination with deravering.

And the daily dose for Latvier, if you use it once a day with deravering, is 0.25 milligrams a day.

But you can also give as Latvier once weekly, it lends itself to once weekly dosing at a dose of

two milligrams. Now remember as Latvier was the drug that when it was used at too high of doses,

decreased white blood cell count, decreased CD4 cell count. So the right dose seems to be for

once weekly dosing two milligrams a day or for daily dosing 0.25 milligrams a day. And in the once

weekly formulation is Latvier, the NRTTI is put with a capsid inhibitor, the only capsid inhibitor

we have so far, which is Lennon Capavier. And the dose of Lennon Capavier that lends itself to once

weekly dosing is 300 milligrams a day. So this particular study is a phase two study, not phase three,

phase two study of looking at the combination of his Latvier and Lennon Capavier once a week,

small study 52 people, compared to big tap FTC once a week. And these were in people who were

already suppressed in this phase two study, phase of this phase two study was looking at the 48

week time point and looking at those results. And then there was an extension phase where everyone

in big tap FTC could go over to his Latvier, Lennon Capavier once a week. So this is the 96 week

results that was presented at Croy 2026 of that extension phase, 96 week data. So half of people

are only going to be on his Latvier Lennon Capavier for 48 weeks, half of them for 96 weeks.

Now the end point is the FDA snapshot analysis of staying suppressed fundamentally. So what did

the results show us? So if we look at again, kind of two groups, there's the people who were early

switched to his Latvier Lennon Capavier. So they got to be on his Latvier Lennon Capavier for full 96 weeks,

their virulotic suppression rate at 96 weeks was 88.5%. There was actually some data that yet hadn't

gotten in window, but there were zero failures at 96 weeks. That's important to say that no one

actually failed at 96 weeks and of all participants who had available data and importantly no resistance

in any of these groups. The second group was late switch groups. So those are the ones that had to be

on big tap FTC for 48 weeks, but then they got to be on his Latvier Lennon Capavier after that for 48

weeks and the virulotic suppression rate there remained high at 97.8% and again of all available data.

So anyone who wasn't in the 97.8% of that 2.2, they just didn't have available data,

any available data, no failures, no resistance of either Latvier Lennon Capavier. So looked good

at phase two data. There are two studies, one's called island one, one's called island two,

and these are two big phase three studies of his Latvier Lennon Capavier once weekly and actually

they are fully enrolled at this point and the data is coming quite quickly and they expect to

present their results. It was Latvier Lennon Capavier from island one and two at IAS in real this summer.

And if that's true, then they will actually be able to and if it's favorable, they'll be able to

file for this once weekly pill by the end of the year. Importantly, it is a combination pill,

even though it's two different drug companies that makes them, they put these pills together in a

combination pill that's given once weekly. So think of your patient populations as we go forward

who's going to want once weekly dosing. There are some people who take their GLP1 agonist once a

week, take their bisphosphinate once a week who just can only take meds on Saturdays.

You know, there's going to be a group that's going to want once weekly dosing. Think about that

group. Think about who you want on BicLenn. Switching over to from to know if they're sparing.

Think who want to be on this Latvier Lennon is Latvier Draverein. We're going to have these three

options actually relatively soon, which is extremely exciting. And then so just to sort of summarize

those four artistry one and two. Again, looking at BicLenn. Switching from a complex regimen looked

good at 48 weeks. It's going to enable the drug company to file for BicLenn. Think about your patient

populations first line Draverein is Latvier non inferior to BicTaf FDC at week 48 in a very

diverse study with lots of diversity in the naive study. And this which study also looked good

at 96 weeks. And then is Latvier Lennon Capiver from BicTaf FDC phase two 96 week data look good.

We need the phase three data that's going to be presented this time.

Okay, thank you, Dr. Gandhi. So let's switch to HIV prevention. So they were

another study presented on HIV prevention. Mostly updates of previously known studies. And I will

start with this French study, the Prevenue Study, which final results were presented. So that's a

cohort study that was conducted in France between 2017 and 2025. And this cohort enrolled HIV

negative adults, a high risk of HIV infection with an itchy for both 50. People could use either

dollar daily or on demand or oral prep with TDFTC. Only Mason could use on demand oral prep

in this study. But people could choose between the two options and could switch between options

during the course of the study. So there were two objectives in that cohort study. The first was

to demonstrate by implementing this cohort study in more than 25 sites in the Paris region that

you would have a decrease in new HIV diagnosis in man websites with men and transgender women

in the whole Paris region by at least 15 percent between the begging of the study and the

end of the study. Also, we looked during that study at the type of procurement that was used

by the participants, the retention in the study, the HIV incidence, and STRs as well as safety,

durability, and sexual behavior. Eventually, the participants were categorized in three groups,

although these nearly four years of follow up in medium participants. So there was a group of daily

user on the left inside of this graph. We used daily prep for more than 75 percent of the

follow up. And these represented 38.4 percent of the preparation. And during the study period,

the median daily use was 100 percent. So these are people mostly using daily prep. And in that group,

incidence of study discertoration was 15 percent. In the on-demand group, in the middle,

those who used on-demand prep for more than 75 percent of the follow up,

represented also 38 percent of the whole population. So they used a median 100 percent of on-demand

prep. And the rate of discertoration was 17.4 percent. And there, there was the switch call,

those representing 23.3 percent of the population. The median daily use of prep was 50 percent.

So they were 50 percent of the time using daily prep, 50 percent of the time using on-demand

prep on average. And they had the lowest incidence actually of study discertoration of 12.8 percent.

Interestingly, when we look at the overall HIV incidence during the study period,

it was very low, less than 1,000 percent years of follow up. So these type of incidence,

are those also reported with non-acting injectable prep agents, whether it's in a cap of

heat or cavitat relief. And the incidence was actually similar across the different

prep regime that were used during the study period. Overall, the safety was pretty good,

as we know with all GDFETC, except that we've seen a higher rate of gastrointestinal

diversity that in those using on-demand prep versus those using daily prep.

We also want to look at the data in the Paris region that these are data from public health

friends, so not coming directly from the study itself. And when you look at those data,

comparing two periods, so 2015 and 2016 in red to 2023, 2024 in blue, you could see that overall

in all men who have sex with men and transgender women, there was only a 2 percent reduction in new

HIV diagnosis, which was not significant. So this was quite disappointing.

However, when you look at MSN born in France, you could see that there was a drop by 33 percent

of the number of new diagnosis between these two period. And as a matter of fact,

most participants in the prevenous study were also born in France. That means that in these

prep studies in France, we were able to enroll mostly MSN born in France and not really MSN

born abroad. And if you see in the graph the incidence of HIV diagnosis among MSN born abroad,

you could see that between the two periods, there was a 73 percent increase in new HIV

diagnosis. And this increase was also seen among transgender women. And so that explained why

overall you didn't see any significant decline in new HIV diagnosis because this decline was

mostly seen in those born in France, those who actually had access and used oral prep.

So interestingly, also at the conference, we had an update on purpose one and purpose two studies,

these large face-free randomized double-blind study, assessing Lena Kepaville, Longat King,

Lena Kepaville, given every six months. So in purpose one, there was among cis-gender women,

young cis-gender women aged between 16 and 25 years. We had known HIV studies that no prior

HIV testing or prior puers in the last three months. And in purpose two, the study was conducted

among cis-gender men and transgender women and transgender men and gender non-binary people,

again, with unknown HIV studies and we had not been on on prep recently in the last three

months. And so you can see that sample size was quite high. In purpose one, the participants were

randomized two to one in either Lena Kepaville arm, the F-taff arm. So it was daily F-taff or daily

TDF-FTC. And in the purpose two study, the randomization was Lena Kepaville versus oral TDF-FTC.

And in primary reports and in the application, we had the results of the week 52, and here

the completed the analysis with the final data when we had monitored all science, all study

visits. And you will see that the results are a little bit different. If you look at purpose one

in particular, so in the primary analysis, you had and that was quite striking zero infection

those young women with serputaneous Lena Kepaville given every six months. In at the end of the

double blind phase, before the open label Lena Kepaville phase, we had two women who acquired HIV

lecture. And there was interesting to see that and we will describe these two women in more

details. In the oral F-taff or oral F-tDF, there were also additional cases of HIV breakthrough

infections. So in total, we had 77 HIV infection if you combine the two oral prep arms and two in the

Lena Kepaville arm. And so it was interesting to see that among these two in the Lena Kepaville arm,

one woman actually discontinued land before being diagnosed with HIV infection, but the other

women was actually diagnosed with HIV infection, but she actually did not discontinue Lena Kepaville

and she had a pretty low viral RNA of 78 copies per ml. On the next slide, we will look at the

data from Purpose 2, so in MSN or Transient of Men or Women. And here again, you could see that

during the primary analysis, we had two individuals who were acquired HIV infection in the Lena Kepaville

arm. And we had one additional individual at the end of the double blind phase who acquired

actually also HIV infection. Similarly, in the TDF-FTC arm, we had nine and now we had 12. So

a couple of more HIV infection also in the TDF-FTC arm. And so if we look at the individual

were acquired HIV infection while on Lena Kepaville, which was not included in the primary analysis,

this was an individual was diagnosed via started testing at week 52 with a pretty high viral load

more than two million copies per ml. And again, these participants received all Lena Kepaville injection

on time with PK concentration, which where actually we deal the range of efficacy. And so we at

this point don't quite understand how this individual could actually become infected. That also

is a reminder that not any pre-precipment can be 100% effective and this rare infection can occur.

On the next slide, we're going to look at the resistance, which emerged either in Purpose 1 and Purpose 2.

And what's important is that we had infection that also were diagnosed at baseline,

before the Kepaville was started. And what you have here is the infection that occurred

while participants were on Lena Kepaville. So we had if you combine Purpose 1 and 2,

five infections. And in this five infection, resistance was emerging in four of them.

So this is important to keep in mind. This was the signature mutation for Lena Kepaville,

which is, as you know, a little therapy for prep. If you look now at the breakfast infection that

we had diagnosed in the combined oral prep arms with FTAF or TDF, among the 89 infections that

we had diagnosed, resistance was identified in only five cases. So that tells you that the

barrier for resistance is higher clearly with FTAF and it is with Lena Kepaville. And so that's

going to be important to look at the additional data on resistance in case of breakthrough infections.

So the key takeaway message from the prevention study was where the following in the

Prevenue study with daily or on-demand oral prep with TDF, FTC, there was a reduction in HIV

diagnosed among French born men. We have sex with men because these were the men who actually

inference have access to prep, but there was no significant change among all MSN and

transgender women because of an increase in HIV diagnosed among foreign born MSN and transgender

women will actually are underrepresented in people using oral prep in France right now.

If you look at the final results of the proposed one and two studies during the double-blind phase

using twice yearly Lena Kepaville, we could say that these results could serve the high effectiveness

of the Lena Kepaville for HIV prevention, new HIV infections were greater, but resistance could

emerge to Lena Kepaville in those who had a breakthrough HIV infection. Lena Kepaville was well

tolerated and injection sac reaction were similar to those in the primary analysis results.

And with that, I'll lend over to Dr. Gendy to the next phase.

Okay, we told you about three probably coming in the next one or two years,

combinations that we can use for HIV treatment and that it's like to redraw wearing daily

Ben Lenn, Bick Lenn daily is like to her Lena Kepaville once weekly. The next part are actually

investigational agents, both treatment and prevention. And these will be coming in longer period of

time, but they're very interesting. So the first one is an NRTTI. So remember that's what

is Lattover is a not a nucleoside reverse transcription. Translocation inhibitor is Lattover's

the one that's coming out once daily once weekly. And as Lattover, there was another presentation,

not this one, about an implant of a Lattover acroi that showed that it didn't seem to work the

implant at the end of the dosing interval against M184V virus. That's going to be a

come important for this next part. And this next part is MKE527. So what is this? This is an NRTTI.

It looks like it lends itself to once monthly dosing and it's only going to be studied for

prep for pre-exposure prophylaxis. And what this was was the actual population modeling to look at

both these sort of phase one trials and then one phase two trial just to figure out the dose.

We really want to just say what was the eventual dose that's going to be studied once monthly for

prep. And that's 11 milligrams. You can see on that column there with 11 milligrams if you look

at trough. And if you look at one hour post initial dose, it gave you the right concentration. So

11 milligrams once monthly is going to be studied in two studies, which are called expressive

10 and 11 that are looking at once monthly MKE527 for prep. Importantly, this is not going to maybe

cover M184V viruses at the end of the dosing interval. And I just think that's important to say

because we have a little bit of worry about that that hopefully we're not going to have it be in

countries with a lot of circulating M184V. So this is going to be studied. The one other thing to

say about once monthly MKE527 for prep, it looks like even though in pregnant women, the levels

do go down some in the second and third trimester, that's okay. It's not going to be dose-adjusted,

so you don't have to get off study. If you become pregnant in the study, you just have to be

reconsented. And then adolescents, there is something about weight. The lower the weight, the higher the

dose, the higher the concentration of MKE527, and it's triphosphorylated compound,

intracellular goes up if you have lower weight. But again, it doesn't look like dose adjustments

are going to be needed. So this, the expressive 10 and 11 studies, there will be allowance of

adolescents at least 16 and 17 year olds. And again, once a month prep, let's see what the

feeds retrials show. And then what about investigational treatment? One is a broadly neutralizing

antibody. So what is this study? This was called the embrace study. And it's a look at

cabitegiver. And then a broadly neutralizing antibody called N6LS, which has been called

low tivabart. And the question of the embrace study is N6LS given either IV or sub-Q

with cabitegiver once a month. Now, the cabitegiver you can see is given once a month in treatment with

the N6LS being given every four months. Now, I remember there's going to be an ultra long

acting formulation of cabitegiver that's given every four months. And there is going to be an

upcoming study looking at N6LS every four months with cab every four months. But this particular

study embrace looked at cab once a month. I am with IV and 6LS every four months compared to

oral sub-Q art. So what's going to formulate and what's going to go forth is the IV formulation

of N6LS. You can see that's the orange bar here. And there was a 94% feralogic suppression rate

in those who were on N6LS IV every four months with cab every one month. I am the sub-Q didn't

work that well. So that's out. And then, of course, oral standard of care art was fine. So this

is going to move forward into the part two of the study looking at N6LS and the PK lens itself

to every six months. And that'll be in part two of the study. And then there's going to be another

study of N6LS every four months IV with cab every four months ultra long acting formulation.

Okay, what's the next drug to be on the lurch for? The next one is an insti. It's long acting.

It's called GS3242. And all we got from Kroy were actually three studies. One was an oral abstract

or shown here. And then there was actually two posters. One's called 490 and the other one's 521.

I'm going to encourage you to look at those posters of GS3242 as well. Now, what this insti does is

it looks like it can have pretty long efficacy at at every four month dosing. And it's a single

intramuscular dose. And you can see that it does drop the viral load in people with HIV.

Strong antiviral activity drops the viral load quickly, just like an insti does. And it looks like

the PK. It's going to lend itself to every six months. Why is that important? It's made by the same

drug company that makes Lena Capavir. Lena Capavir is every six months. So likely GS3242 is going to

be able to be extended every six months and be given with ultimately tested with Lena Capavir

every six months. Importantly, if you look at poster 521, you can see that 3242 does have activity

against some insti mutations, at least in vitro, for example, N155, Q92, E92, Q, and also Q148.

And even R263. So what about the other two in experimental agents that we're going to be

able to look out for? The next one is also a long acting insti. It's called VH184. And the

presentation in the oral session that you can see down below just looked at its safety PK and

antiviral, but in an IM and a subcutaneous formulation. And this, this is not being tested every

four months. Right off the bat, it looks like it will enable every six months dosing. So an insti

every six months. Maybe you can put it with Lena Capavir. Maybe you can put it with a new

a capsid inhibitor that the same drug company's producing, which is VH499, which we'll talk about next.

So VH184, one thing to remember, and there's a poster on this, is that it looks like it also

works against insti mutations. We had seen this data before. So VH184 may work against

Dolategiver resistant mutations, which could be very intriguing to have kind of this,

now we're in the third generation of inner race inhibitors. So VH184, every six months,

IM said Q, it's going to be studied in a phase to be in a vague study. And what's the final drug to

remember? It's called VH499. This is going to be the next capsid inhibitor that's developed.

We only have Lena Capavir so far. And this was a phase one study that looked at again,

either sub Q or IM of this new capsid inhibitor. It lends itself to every six months administration.

It's made by the same drug company that makes VH184. So VH184 and VH499 will eventually be studied

every six months for treatment. And it will move on to its phase to be studied, which is the

Synergy Study in 2026. So those are the four new drugs that we need to look out for N6LS,

VH284, VH499 and GS3242. And now we want to answer your questions. Thank you so much for your attention.

Thank you, Dr. Gandhi and Dr. Molina. We do have some questions in our queue from our audience.

So if you would like to discuss how often do you see HIV after surgery or post-transfusion

in adults and kids? After skin grafting on both patient types post-op?

You know, I would just say not seeing this at all because of the, you know, so the blood supply

is really, really safe at this point. So I've never seen a seroconversion after these kind of

procedures. What about you, Shamishal? Well, that's the same now. You know, this is now something

we see anymore. You know, we've seen a lot of people becoming HIV infected after blood transfusion,

but that was back to the 80s, the 1980s. So since the, you know, the blood now is being tested

in France at least, not only for antibodies against HIV, but also for RNA against HIV. So we

every single blood donation is status for antibody and HIV already. And so I think with that,

it's a costly strategy, but it makes the blood transfusion very safe.

But I can't just say that it's not possible everywhere. And so in some countries that might happen

that you may get HIV infection for blood transfusion is the blood bank is not

secure or tested. Though, you know, it does bring up the idea of prep in transfusions and in those

who use drugs and inject drugs. And I would say that this point we have pretty good evidence at

least for oral prep that that works in transfusion. Well, at least in persons who inject drugs from

the original Bangkok TFE study. Right. And there is, as you know, another study with Lena Kepaville

that is being implemented also in IV drug users. So that's going to be also interesting to

demonstrate that Lena Kepaville would also be able to prevent each other's position in HIV

drug users as well. So we don't have the results yet, but this is probably something we'll learn

at age 2026, eventually. You know, since we have a minute, and I don't see another question in

there, I wanted to bring up hepatitis B, because I thought it was a good time to do so. There was

a lot of talk at this meeting, so I'm sure about hepatitis B reactivation, the question of that

with to know for their sparing regimens, because not only is long acting ART with Cabral to know

for their sparing, Len Cabas to know for their sparing, but so are all these new combinations that

we just talked about as a lot of our traveling, then let Big Len, it's a lot of our Lena Kepaville

once a week, they're all don't have hepatitis B activity. So what do you think about, you know,

there was a maybe just mentioned verbally, the scenic study that looked at hepatitis B in the

context to know for sparing regimens. Right. In that very large study, actually, the incidence

of rape through HPV infection was very low in fact, and so this is probably a rare event,

but I think still we have to be careful where we start these, you know, to know for the sparing

regimen, especially if there is no activity against HPV, if you don't have any 3TC or FTC in that,

you know, regimen, I think it is probably worth checking the HPV serology and to see whether

these people might be able to reactivate HPV and, you know, this is, again, this was a rare event,

we've seen also that people using the combination of injectable cavity with a little peary,

and a few people were able either to reactivate or to acquire HPV. So I think if a person doesn't

have any antibodies against HPVS or HPC, then, you know, we should probably provide vaccination

in these individuals. In the others, I think we probably need to be a bit careful, and especially

if we don't have any idea about their DNA for HPV before starting ART, maybe that's something

that would need to be checked. Although, again, we haven't seen, you know, clinical or clinical

reactivation really in those individuals, but they were mild reactivation with mild decrease in

health ease. But I agree with you that the message of this and tight, you know, we saw

applause at the microphone when people said we should be vaccinating people for hepatitis B

everywhere. I think that was one of the biggest messages, and the other is not to use

to know for your sparing regimens and those with hepatitis B surface antigen positivity,

which really means that you want to screen everyone for hepatitis B surface antigen at the

beginning. And if you're core antibody and surface antibody negative, it's core antibody positive

surface antibody negative vaccinate. And if you're core antibody positive surface antibody positive

you're good. And then if you're core antibody positive, it's fine. Like use the to know for your

sparing regimen, but watch the people. It can be tricky with hepatitis B, and I think you're,

you know, as you said, eventually these are rare events, but when they occur, it can be a bit

shocking for the people because they do not expect that then we should tell them that, you know,

if they don't have any protection against HPV, yes, they should be vaccinated. And then one thing is

because this is a good question that Dr. Kaplan Lewis asks, would you not even consider long

acting cabral and those refuse hepatitis B vaccination? I would say that there was another message

that came out that if you are only going to take HIV therapy by long acting, then go ahead and

do it. And I will say that we had a focus group at the lead meeting where people said, okay,

if you refuse to know for fear and you have hepatitis B, but you'll get, you have an opportunity

to get your HIV treated, then treat your HIV. So I don't think Emma that we would like, say,

absolutely no, you cannot have long acting cabral. But we'd really support that getting

happy vaccine. And then I think we could just end with this final question by Nuguri, Dr. Nuguri,

which I think is a really good one, which is the Lena cap of her resistance because, you know,

there is this worry that if you roll out land that we're going to get with prevention,

we're going to get resistance and we won't be able to use it for treatment. I'd like your thoughts,

Jean-Michel, but I will say one thing, that boy that the genetic barrier to resistance to land

is probably higher than we thought. And there was a lot of pretty pictures at this

croix about the capsid inhibitor and how strongly Lena cap of her binds there. And I think it's

just a higher genetic barrier than we thought, which is a good thing. Well, you know, I think you

know, the talk on capsid inhibitor was fantastic at the moment. That was one that highlights

of the conference, indeed. Regarding Lena cap of her resistance, I think, you know, we don't know

yet the full picture. And I think the cap of her is being, you know, used for prevention and also

for treatment. I think, although in the data that you presented so far, there was limited evidence

of resistance emerging in those being HIV infected and treated with Lena cap of the

base regimen, let's say. I think this is also something we need to keep monitoring, because

we don't want to jeopardize the use of Lena cap of her prevention. This is such a great

prevention strategy soon being able to be used only once a year and try less slowly. So I think

we should make sure that Lena cap of her would work. Indeed, this is only more than therapy.

And, you know, I think we've seen that in the rare cases of breakthrough HIV infection in those

will use Lena cap of her. You know, of course, we focus on the rare events. And, you know,

I mentioned the individual who had breakthrough HIV infection despite on time injection within

a cap of her. And pretty good actually PK concentration and plasma. So we don't fully understand

why this individual acquired HIV. We can only say this is rare. But in case of HIV infection

on Lena cap of her, you bound to see resistance. And resistance with pretty high plasma

are in a level, which is different from what we've seen with cap of her. So it seems that we

know how the advice central we see with cap of her with Lena cap of her. I do have time to show

that there are, but they were presented also at the conference because in both purpose and purpose

tool, there were a few individuals we were infected at baseline and still received Lena cap of

her. And when they looked at their viral load at baseline, they found that people were already

infected, although they do have any antibodies within HIV. In these individual also, there was

emergence of resistance to the rare cap of her. At least 50% of those people. So that means that,

you know, no drug is perfect. Yeah, no drug is perfect. Yeah. That's absolutely necessary,

I think. Yeah. But we, we're going to see resistance. Never use monotherapy.

Yeah. Thank you too much. You're welcome. Thank you, Dr. Condi and Dr. Melina. And many

thanks to you, our listeners, for joining us. To view the full program and download the

accompanying slides, please click the link in the show notes. To get access to all of our new podcasts,

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Thank you. And have a great day.