Long-Acting Prevention and Treatment of HIV: CROI 2022 Part 2

At the virtual Conference on Retroviruses and Opportunistic Infections (CROI), researchers presented multiple abstracts that could change prevention and treatment strategies for HIV.

MedPage Today brought together three expert leaders in their field -- moderator Monica Gandhi, MD, MPH, of the University of California San Francisco, Carlos del Rio, MD, of Emory University in Atlanta, and Renee Heffron, PhD, MPH, of the University of Washington in Seattle -- for a virtual roundtable discussion on the 1-year data from the CAPELLA and CALIBRATE studies, which looked at the safety and efficacy of lenacapavir, as well as ATLAS-2M, which looked at the long-term findings of cabotegravir plus rilpivirine (Cabenuva) injections. This is the second of four exclusive episodes.

Following is a transcript of their remarks:

Gandhi: I think it would be good to talk a little bit about lenacapavir, and then Carlos, I would just ask you to give us an update on ATLAS-2M, if that's okay, because that's sort of going out to 152 weeks, and lenacapavir is our other exciting, long-acting agent, but this is the longest of all. This is really the idea of giving it every 6 months as a subcutaneous injectable. So that is pretty interesting.

And there was a study out to 54 weeks presented at CROI, which is the CALIBRATE study, which we actually have the 26-week data. And now it went out to 52 weeks.

And remember the design of this study is in naive individuals. So it was lenacapavir sub-Q [subcutaneous] in two arms given with different things. One is going to be bictegravir and one's going to be TAF [tenofovir, alafenamide, fumarate] -- FTC [emtricitabine] at the beginning. And then the third arm is lenacapavir orally with F/TAF. And then the fourth is bictegravir as the comparison with TAF–FTC.

And essentially it went out to 52 weeks. We already had the first subcutaneous injection results at 26 weeks prior to this, and this is the 52-week data that showed that the lenacapavir subcutaneous arms, either with TAF or bictegravir, they're going to go on to be just alone with a single drug.

Right now is kind of collapsed with F/TAF. The lenacapavir subcutaneous is doing just as well as giving lenacapavir orally every day, and the subcutaneous is given every 6 months. So that's pretty fascinating in terms of virologic suppression rates in treatment-naive individuals.

And the ones who did the best are those who are suppressed at week 28 -- as you'd expect, they stay very suppressed at week 52. So there's those who kind of went back and forth with the virologic suppression and had about 85% virologic suppression rates at 52 weeks. And they were 92% if they were suppressed at 28 weeks.

And so that's the CALIBRATE study. And then the CAPELLA study is going to be the one that will get more and more results on in those who go out to those who are multidrug-resistant [MDR] HIV. And essentially we had some secondary endpoints here for the 52-week data for those who have it in MDR HIV, getting lenacapavir with an optimized background regimen. And just a few more participants to look at, going out to week 52.

And really you need some in your background -- you need something to support the lenacapavir. So those who had two or more active agents had a 94% neurologic suppression rate. But if you are just on lenacapavir alone, very few patients are at 67% virologic suppression. So you really do need a backbone for lenacapavir like you do for any other agent.

And then finally putting these two together, the CAPELLA and CALIBRATE, there is some ability to get capsid resistance. So they do occur. There was about two out of 137 that occurred in the CALIBRATE study, where you can get resistance to the capsid inhibitor. So it's not that it doesn't occur, so we have to keep our eye out for this.

del Rio: But I think, Monica, both studies are very exciting.

Gandhi: Yes.

del Rio: And I think CAPELLA, again, you say only 67% virologic suppression on one agent. I mean, these individuals have multidrug-resistant HIV, and thank God we don't have many of those patients anymore because, the current regimens, the people that we have with multidrug-resistant HIV, are the people that started therapy many, many years ago, decades ago. But now it's less common, but I still think it's a group of patients in which we have our hands tied. And I think having an agent that can give you some options, I think it's really wonderful.

Gandhi: Good point. Yeah, you're right. Because if I think about the VIKING study with dolutegravir -- dolutegravir kept them all doing well at 78% virologic suppression when there was hardly anything in the backbone. So that's a fair point. We need these agents.

And then, Carlos, ATLAS-2M was presented there as well, but it went out to 152 weeks.

del Rio: You know, I think ATLAS-2M is very important. As you know, ATLAS, the original study, was about treating with the combination of again, long-acting agents, cabotegravir rilpivirine. And the difference is that the original study was with injections every month, and now we've gone to injections every 2 months, and that's the ATLAS-2M study.

And I think what's really important about the study is that it showed that this works just as well, and you get excellent biologic success with injections every 2 months as compared to every month -- again, talking about the high efficacy of these agents and the fact that you can actually get people almost close to 90% suppressed in the follow-up on the study at week 152.

So the reality is that this has allowed now the FDA to approve the use of cabotegravir rilpivirine in every-2-month injections. And that really is, again, a game-changer, because it decreases the number of times you have to see people; it decreases the number of injections an individual has to receive.

So it's all good news, right? I mean, to think that you can actually treat HIV with six injections per year, to me is mind boggling when, at least I'm old enough to have started when you had to give AZT every 4 hours, right? And now you can give six injections per year. That to me is just simply amazing.

Gandhi: What I really liked about ATLAS-2M going out to 152 weeks is if you make it to be able to go to every 8 weeks, kind of a lot of that resistance that does happen, which is still very rare, is early on. And it kind of looks like all these long-acting studies, the longer you go, people are really good about sticking to the regimen. I know it was a clinical trial, but hopefully they'll do that in clinical care, and you get less and less problems with resistance going forward. So only one additional person got it.

del Rio: And again, this is going to be about choice, right? This is going to be about, I may be somebody that wants to take pills every day, but there are individuals that may want to take injections. And I think we heard a wonderful symposium at CROI talking about these issues and what we've learned from contraception and how this applies to long-acting agents and choice, and PrEP [pre-exposure prophylaxis].

But it could also be on treatment. So Renee, maybe you want to talk about that. Because to me, it was just eye-opening to think about it that way. Because I always think what's best from a biological standpoint, and realizing that that's not necessarily the best from a patient standpoint, right?

Heffron: That's right. That's what Dominika Seidman brought up today [Feb. 22, 2022] during the [CROI] symposium on HIV prevention choice. And if you take a patient-centered perspective, from a contraception angle, one of the counseling approaches that's been applied is this efficacy-driven approach, where you would say for contraception, the longer-acting methods are more efficacious.

And so you would offer those first if you're a clinician. And her point was that doesn't always align with people's preferences and what they would like to do. Sometimes a daily pill is better. And so even though it might not be more efficacious, they can take it better. And in the end that is better effectiveness.

There was also a nice talk by Kenneth Ngure from the REACH [Re-Engage Adolescents and Children with HIV] team looking at results of a very cool crossover trial design, where at first women were assigned to use either the dapivirine vaginal ring or daily oral PrEP. They used that, and then they switched to use the other one. They used them each for 6 months, and then there was this additional 6-month period where they could choose the method that they wanted to use.

And interestingly, about two-thirds of the women chose to use the vaginal ring. This is after they've experienced both options. And adherence was actually better to the vaginal ring when people had chosen it. So even though it may be less efficacious, they're using it. And in the end, that's probably more protection than they would've had if they had to use a daily oral pill, and couldn't use it every day or couldn't use it at all.

So I do think that the story and how to do and how to deliver choice is definitely something that we're all learning a lot about and going to be very important that we keep front and center as we move to a field with multiple options for both HIV treatment and prevention.

Gandhi: I mean, then we already mentioned this, but referring back to Dr. Chloe Orkin's talk on HIV treatment and prevention, she talked about how we agitate for more options for our patients. And, that's how we've gotten to where we are today with long acting. So I think that was an amazing way to start her talk.

Watch episode one of this discussion: Long-Acting Prevention and Treatment of HIV: CROI 2022 Part 1

Watch episode three of this discussion: Second-Line Dolutegravir for HIV Favorable to Other Boosted PIs

Watch episode four of this discussion: Third 'Cured' HIV Patient Headlines CROI 2022

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