ARTISTRY-1: Simplifying HIV Treatment for the Most Complex Cases

Today at AIDS 2024, the 25th International AIDS Conference from the International AIDS Society, Sorana Segal-Maurer, MD, principal investigator on the ARTISTRY-1 trial (NCT05502341), presented 48-week data from the phase 2, randomized, multicenter study in the abstract, “Efficacy and Safety of Bictegravir Plus Lenacapavir: 48-Week Outcomes in Virologically Suppressed People With HIV-1 on Complex Antiretroviral Regimens at Baseline.”¹

These most recent updated data build on 24-week results previously presented.²

ARTISTRY-1 is a phase 2, randomized, multicenter study that looked to enroll virally suppressed persons living with HIV who were on complex antiretroviral treatment and to offer them the possibility of switching to a simplified regimen of once-daily bictegravir plus lenacapavir.

Director of the Dr. James J. Rahal Jr. Division of Infectious Diseases at NewYork-Presbyterian Queens and professor of clinical medicine at Weill Cornell Medicine, Segal-Maurer has been extensively involved in all phases of clinical research for 31 years, much of it spent investigating all of the current antiretrovirals being utilized.

“In general, we don’t really focus on people with HIV who are virologically suppressed, because they’re suppressed. We don’t always think that it’s burdensome to take multiple pills a day. And these persons are getting older, they’re having more metabolic comorbid conditions, more drug interactions,” she stated. “This is the population of persons with HIV that was singled out as sort of being left behind—just because they’re suppressed. I think maybe we put them out of our mind.”

At the time of our interview, Dr Segal-Maurer was director of infectious diseases at NewYork-Presbyterian Queens and professor of clinical medicine at Weill Cornell Medical College of Cornell University. On August 15, she will join the Global Medical Affairs division of Gilead, where she will both continue and expand on her work in infectious disease and HIV.

Transcript

What is the patient population for ARTISTRY-1, and what are your outcomes of interest?

I like the focus of the study: Let's make their lives simpler. Let's make those drug interactions better, or less. That is sort of the overarching goal of the study. And as you would think, if that is your entry criteria, the median age was 60. The majority of participants had been taking antiretrovirals for 27 years, and the median number of antiretrovirals they were taking was 6. Eighty-one percent of participants had a history of resistance to prior antiretrovirals. It was a complex group—but they were all virally suppressed. So it was a great opportunity to step in.

When we looked at the medications they were taking, almost three-quarters of them were on a boosted protease inhibitor [PI]. And what that means is there's a food requirement, there are drug-drug interactions, and there's potential for metabolic side effects. And of those, they were taking not just a boosted PI, but multiple other agents. Almost half of them were taking medications twice a day, and a third of them were taking 5 or more pills a day. So you can see how this is a population when you say to them, “Maybe there could be something once a day,” I think it's a tremendous study to offer persons with HIV.

How do bictegravir and lenacapavir work individually against HIV, and what are the benefits of combination treatment?

Bictegravir is a guideline-recommended, almost best-in-class integrase inhibitor, and it's part of bictegravir F/TAF [emtricitabine/tenofovir alafenamide (Descovy; Gilead)] [Biktarvy; Gilead], which is one of the major guideline-recommended single-tablet regimen combinations. It has a high barrier to resistance, which is very important because as I've mentioned, this particular population of persons with HIV has a history of resistance. So it's important that bictegravir comes to the table having that high barrier to resistance. Lenacapavir is a first-in-class capsid inhibitor, where there's no underlying resistance that persons with HIV would have if they've never taken it. So the 2 together can really offer a significant benefit or a potential for a good combination if somebody has prior history of resistance.

The other thing that's important about each one of those 2 medications is they have very limited drug-drug interactions and no food requirement. So when it comes to some of their tolerability, some of the safety profile, the adverse events that they've been shown to have in studies, they're very favorable, very limited adverse events. Certainly, we've seen lenacapavir in the CAPELLA trial, very limited adverse events.³ So it's interesting to put those 2 together, because they can offer significant advantage to this population of persons with HIV.

Can you explain how these new 48-week data build on the 24-week results?

What the 24-week data showed—which dovetails into the 48-week data as well—is that first of all, there was significant efficacy.² When these persons with HIV were either maintained on what they were taking or they were switched to either 1 of 2 arms, bictegravir 75 mg plus lenacapavir 25 mg or bictegravir 75 mg plus lenacapavir 50 mg—so it was a total of 3 arms—regardless of what arm the participants were in, the efficacy was very high at 24 weeks. And the data that I'll be presenting tomorrow¹ show that that result was durable, and the regimen maintained efficacy through 48 weeks.

The other thing that was shown at 24 weeks was that the treatment-emergent adverse events, or the side effects that occur as a study is ongoing, were very limited. The combination was very well tolerated. The other thing that was very interesting is regardless of the dose of lenacapavir, the dose of bictegravir remained the same in the 2 arms, but then lenacapavir was 25 mg and 50 mg. There was no significant difference in terms of either efficacy or adverse events of either of those 2 doses.

And the data at 48 weeks remains very similar to 24 weeks, which, as an investigator, that's always encouraging. Because sometimes we say, “Well, the short-term data is very good, but let's really see what happens in longer-term data.” So both of those things remained consistent through 48 weeks.

Why is it important to include diverse patient populations in HIV/AIDS clinical trials?

I think diversity in studies is incredibly important. As you rightly pointed out, females at birth were 19%, and Black race was 31%. I think it's important to have diversity, because sometimes there may be particular efficacy or adverse events that may be reflected in one population, not another. From a clinical point of view, when you see a patient and you're counseling them that you could take this or you could take that, their first question is, “Oh, how will I do with this or with that,” and I think it's so important for the studies to mirror who the patients are when the study is finished, when those medications may be prescribed. Because I think it's important for patients to understand that we studied patients similar to you and this is how they did. I think it goes a very long way in helping them understand that there is safety. It's not that no one looked at someone like you so who knows how you will do.

What are your next steps in this investigation?

The next steps after the 48 weeks are to go to the next phase, which is ARTISTRY-2. There is a single-tablet regimen now of fixed-dose bictegravir 75 mg plus lenacapavir 50 mg that will be used in that next phase. It's very exciting because the separate tablets that were given in that first ARTISTRY-1, now in ARTISTRY-2,⁴ it'll become a single tablet once a day. I have to say I feel the excitement on the participants’ behalf, because those who have been randomized are no longer taking these complex regimens. So that is the next phase, and there's a lot more data that will come out.

References

1. Mounzer K, Slim J, Ramgopal M, et al. Efficacy and safety of bictegravir plus lenacapavir: 48-week outcomes in virologically suppressed people with HIV-1 on complex antiretroviral regimens at baseline. Presented at: AIDS 2024; July 22-26, 2024; Munich, Germany. Abstract OAB2602. https://programme.aids2024.org/Abstract/Abstract/?abstractid=1

2. Mounzer K, Slim J, Ramgopal M, et al. Phase 2 study of switch to daily BIC + LEN in individuals on a complex HIV treatment regimen. Presented at: 2024 Conference on Retroviruses and Opportunistic Infections; March 3-6, 2024; Denver, CO. https://www.croiconference.org/abstract/phase-ii-study-of-switch-to-daily-bic-len-in-individuals-on-a-multitablet-hiv-treatment-regimen/

3. Segal-Maurer S, DeJesus E, Stellbrink HJ, et al; CAPELLA study investigators. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection. N Engl J Med. 2022;386(19):1793-1803. doi:10.1056/NEJMoa2115542

4. Study to compare bictegravir/lenacapavir versus current therapy in people with HIV-1 who are successfully treated with Biktarvy (ARTISTRY-2). ClinicalTrials.gov. Updated June 21, 2024. Accessed July 24, 2024. https://clinicaltrials.gov/study/NCT06333808