Long-Acting Injectable Cabotegravir/Rilpivirine for HIV

MedPage Today brought together three expert leaders for a virtual roundtable discussion on HIV news from the IDWeek annual meeting: Moderator Monica Gandhi, MD, MPH, of the University of California San Francisco, is joined by Kathleen A. McManus, MD, of the University of Virginia School of Medicine in Charlottesville, and Laura Bamford, MD, of the University of California San Diego School of Medicine.

This first of four exclusive episodes examines data from the OPERA cohort on cabotegravir-rilpivirine (Cabenuva) as well as its effect on hepatitis B patients who switched to the therapy.

Following is a transcript of their remarks:

Gandhi: Hi, my name is Dr. Monica Gandhi, I’m a professor of medicine and the medical director of the Ward 86 HIV clinic at UCSF. And I’m really excited to talk about the HIV news out of IDWeek for MedPage today. And Dr. Bamford, you’re joining me, please tell us about yourself.

Bamford: Thank you, Dr. Gandhi. I’m Laura Bamford. I’m an associate professor in the Division of Infectious Diseases and Global Public Health at UC San Diego and also the medical director of the HIV Medicine Clinic here, the Owen Clinic. Dr. McManus?

McManus: Hi, I’m Kate McManus. I’m an assistant professor at the University of Virginia and the medical director of the University of Virginia Ryan White Clinic.

Gandhi: So there were some really interesting things out of IDWeek, I thought. And I think if we want to divide them, we could think about dividing them into the long-acting injectables, which there’s just more and more data on. There were effects of weight and hepatitis B and then some on PrEP.

And to start with the long-acting, there hasn’t been a lot of data out there about using long-acting injectables in viremic patients or participants. There was a small University of Mississippi study published over the summer in CID [Clinical Infectious Diseases], and our clinic, Ward 86, has done some work looking at long-acting cabotegravir and rilpivirine in viremic patients.

But this was nice to see at this meeting the OPERA study, which is really a large retrospective cohort study of patients in care across the U.S. Actually I believe 14% of patients living with HIV are represented in the OPERA cohort. And because now long-acting cabotegravir and rilpivirine has been out for 2 years more, there’s certainly providers out there who are trying the use of these medications in patients who start with viremia and cannot take oral ART [antiretroviral therapy].

And so there were kind of two abstracts at the meeting that discussed this, but I think the most notable one was really looking at those in the OPERA cohort who had started with a viral load of greater than 50 and of those patients 50 copies/mL and there were 229 of those patients. So they started with greater than 50 copies/mL, got put on long-acting cabotegravir-rilpivirine and their viral load, if we had enough measurements essentially, their viral load was suppressed less than 50, 82% of the time and less than 200, 94% of the time. So it kind of mirrors what we’ve seen in these other smaller cohorts that does look like it works in patients with viremia.

I wonder what you thought about that? It was the largest kind of database to add to this question.

McManus: I think it’s great to see this from different angles to see it from your clinic, now to see it in this retrospective look. I think it just adds more evidence and more data that hopefully we’re going to be able to do this more widely through more clinics.

Gandhi: Yeah, I think this is going to give it a boost, this question of using it in viremics. And I have to say, I don’t know if you all saw Dr. [Paul] Sax’s NEJM Journal Watch commentary that he put out on September 25, 2023, but he said, if you can’t take oral ART, there is a role for long-acting even with the small studies we have. And he wrote about that prior to the OPERA analysis. So I think that’s just going to get more credence to, is this going to ever be in the guidelines as a, again, only if you can’t take oral ART, but if you can’t take oral ART, your chances of success is zero. So I think this was intriguing retrospective data.

There were also some comorbidity data, Laura, and I was wondering what you thought about that with the hepatitis B? Because one thing I will tell you is that we have been trying to be really careful when we switch patients to cabotegravir-rilpivirine about reminding ourselves about patient’s hepatitis B status and really tracking that because of course cabotegravir-rilpivirine don’t work against hepatitis B.

Bamford: No, that’s a very good segue. So this a study that was presented at IDWeek from a VA cohort of patients who did exactly that, switched off a regimen that included hepatitis B treatment mostly to cabotegravir and rilpivirine. And while reactivation was rare in this cohort, it wasn’t zero, about 1.5%, but this was also performed in the U.S., which we don’t think of as an endemic area for hepatitis B. Reactivation was more common in participants who were core antibody alone, so probably those that either lost surface antibody over time or their surface antigen was now at undetectable levels. So in participants that were HepB surface antibody and core antibody, even lower levels of reactivation, but also not zero.

And so I think, like you said, Dr. Gandhi, we need to be very careful in switching patients and really I think discussing with them with shared decision-making, are patients willing to take that risk to come off of an all oral regimen.

McManus: Yeah, I think this was a great study, because this is definitely something we come across in the clinic, either seeing patients who maybe other clinics switched off of HepB active therapy and wondering, wow, did they just get lucky? Or this person didn’t reactivate, what should we do now? So I think this definitely gives us kind of a number to talk to patients with that shared decision-making.

And then I think even the team pointed out, the team that did this study, that a previous study showed a reactivation rate of 10% in Cameroon. And so kind of knowing that it might span somewhere from the 1.5-10% depending on different areas or different sorts of other circumstances.

Gandhi: Yes. I mean, sorry, I was just going to say that we have tried to pay attention to it, but if we don’t do a recent hepatitis B core antibody surface antibody surface antigen, we may have made assumptions that the surface antibody is still positive and that the patient is immune. And so now we’re pretty rigorous when we use cabotegravir and rilpivirine to repeat those serologies and to ensure that we know where they are with their current hepatitis B status.

Bamford: And I think based on this study, if we then find that someone is core antibody positive, one, checking for HepB DNA levels, but also vaccinating them for HepB and make sure they’re achieving surface antibody because that seems to lower the risk. But we can also be vigilant, but then if our patients are going to oncology or rheumatology and getting other immunosuppressive agents, we really have to remind patients that they do at that point need to go back on their hepatitis B treatment.