Long-Acting Antiretroviral Therapy in Patients Without Viral Suppression

In this video, Monica Gandhi, MD, MPH, discusses the results of her team's recent study which examined the use of long-acting antiretroviral therapy (LA-ART) in individuals with HIV with viremia, which is currently only approved for use in patients with HIV with viral suppression.

Additional resource:

• Gandhi M, Hickey M, Imbert E, et al. Demonstration project of long-acting antiretroviral therapy in a diverse population of people with HIV. Ann Int Med. 2023;176(7):969-974. doi:10.7326/M23-0788.

TRANSCRIPT: 

Consultant360: To begin, could you give a brief overview of your study?

Monica Gandhi, MD, MPH: Yes. So I am the medical director of Ward 86, which is a large HIV clinic for publicly insured patients in San Francisco. And we were really excited like the rest of the HIV community when the long-acting medications came out. We have had oral medications for HIV since 1996. They've been getting better and easier, but actually it's hard for some patients to take oral medications every day. We have seen that in the fact that the CDC just last week at the Medical Monitoring Project released updated estimates of those who are on treatment, virologically suppressed, and were only at about 59%. So it means it's hard to take oral ART every day. So we are excited about long-acting injectables and we started them pretty early on in our clinics, both in patients that fit the criteria of how long-acting cabotegravir and rilpivirine, which are the two agents that are currently improved, should be used, which are patients who have taken oral ART and are suppressed. But we also tried them out on patients who just could not take oral antiretroviral therapy and who were not suppressed with their viral load and that was our project.

C360: What are some of the potential benefits and drawbacks to administering LA-ART in individuals without viral suppression?

Dr Gandhi: Well, it's a really good question because we published our results in Annals of Internal Medicine on July 4th. But the reason we called it a demonstration project is because if you look at the FDA guidance and how these drugs are approved, the clinical trials have studied long-acting cabotegravir and rilpivirine only in patients who can take their oral ART every day and are virologically suppressed. And actually we think that these would be of great benefit to patients who can't take oral ART because the whole point, if you can't take oral antiretroviral therapy because of housing insecurity, food insecurity, substance use, mental health issues. there are lots of reasons why people have a hard time taking their drugs every day. We were hoping this could be an option for those patients because instead of leaving them out and saying, well, you know what, we don't have anything for you. We have the long-acting injectables. They've been approved by the FDA. Providers are allowed to prescribe them in the way that they see fit for their patients. And so we tried prescribing them even in patients with viremia because our idea was there'd be a benefit to getting some patients suppressed for the first time in their lives if they couldn't take oral ART. And actually that's what we saw.

C360: Could you discuss how LA-ART may change the treatment landscape for individuals with HIV?

Dr Gandhi: In our demonstration project, and we're going to present updated results at an upcoming meeting, but we basically, for the first 133 people that we started on long-acting cabotegravir and rilpivirine, about half were viremic, about half started with virologic suppression. And the overall rate of virologic suppression was really high, about 98.5%, which is really the same rate that was in the clinical trial. So there's a certain amount of failure, but it's very low. And we even saw that with our patients without virologic suppression.

So I think there's two ways that this study could change paradigms of treatment. One is I do think a lot of people, because we presented this at a major meeting and we published in a journal, a lot of people out there are starting patients, HIV providers are starting patients on long-acting cabotegravir and rilpivirine, even if they're viremic based on our experience of Ward 86. And they're just seeing the advantages of that. So hopefully we'll have a lot of people putting data out there to help instruct us on how to do this.

The second thing that I think is really important is that the pharmaceutical company that makes these drugs is launching a trial now on studying long-acting cabotegravir and rilpivirine in viremic patients. So we're going to have a single arm trial. It's not going to be randomized, but just a single arm trial, kind of a bigger demonstration project by the drug company across sites. We're having individual demonstration projects going on, lots of people are doing it. We'll put all that data together and I think we're going to see that these injectables really have a niche for those who just have so many challenges in their life to taking oral ART and they just can't take a pill every day.

C360: What are the next steps for research in this area? How will these next steps in research bring us closer to a potential FDA approval of LA-ART in individuals with viremia?

Dr Gandhi: It's a really good question because the FDA has essentially said to the drug company, and they're the ones who work together to get approvals for drugs, the FDA said we're seeing these demonstration projects. This looks like it's working for people, but we want not a randomized trial because it really looks like these long-acting cabotegravir rilpivirine is working for viremic patients. So we don't need a randomized trial where you randomize half to taking it if they're virologically suppressed and half of their viremic. We just need a single arm trial where one group of people living with HIV across different sites without virologic suppression are put on this agent long-acting cabotegravir and rilpivirine. And if that looks good like the demonstration project looks good then we can approve this, put this formally into the FDA guidance. So that's starting, that trial's really going to start soon.

And then the second lines of research is a lot of people are out there putting out abstracts, putting out kind of commentary on yes, we've been using long-acting cabotegravir and rilpivirine as well. And in fact, it's really interesting that we had a commentary on the Annals piece that was written by some HIV doctors and they said more people should be doing this, but if they're going to do it, put out the information so that we can all learn from each other on using long-acting cabotegravir and rilpivirine in viremic patients. So it's kind of launched a whole idea.

And then there's one other thing that's happening, which is that the one drawback with cabotegravir rilpivirine is rilpivirine is what's called a non-nucleoside reverse transcriptase inhibitor, NNRTI. And in the world there's a certain amount of NNRTI resistance because NNRTIs were first-line therapy up until relatively recently and now integrase inhibitors are first-line therapy. So there's resistance out there to NNRTIs. And in fact, to be fair, the World Health Organization has not approved long-acting cabotegravir and rilpivirine for the planet. They've said worldwide we're worried about the NNRTI resistance rate.

So we are now doing a pilot looking at cabotegravir, not combined with rilpivirine, but actually combined with another long-acting agent that just got approved in December for multi-drug resistant virus and that's called lenacapavir. Lenacapavir is a capsid inhibitor and we're assembling a case series of lenacapavir and cabotegravir being used in patients around the United States who have NNRTI mutations. We'll put that case series together. We're going to submit it to a conference and hopefully that'll launch a discussion that there is going to be a need for other long-acting agents in patients who can't use rilpivirine. So I think that's going to be the next line of more experimental research. Next is to do a trial of lenacapavir cabotegravir in NNRTI resistant patients.

C360: Is there anything else that you would like to add to our discussion today?

Dr Gandhi: One thing that it's really hard to say in a paper that we put out this paper is how patients feel. And I will say that we asked a lot of our patients, well, you couldn't take these oral ART but get it. How does it feel? You're on these long and you're actually coming back for them. And some of my patients said to me, “Well this is the first time that I've ever been virologically suppressed in my life. And I used to be embarrassed to come to clinic. It would make me actually use maybe substances or something I was embarrassed without being able to take the oral ART.” And I think there's a de-stigmatizing effect to using long-acting when you just haven't been able to suppress. So it's hard for me to convey, except in interviews like this, that it really has helped a lot of our patients at Ward 86. And we're really, I think the is riveted by long-acting ART in the HIV world. It's kind of all we talk about at our meetings, and it's exciting to think of different uses for these agents.