Advances in HIV Treatment Strategies

In this video, Monica Gandhi, MD, MPH, discusses advances in HIV treatment strategies, including treatment for naive patients, treatment-resistant patients, and patients on long-acting ART. She also discussed these topics at the Conference on Retroviruses and Opportunistic Infections (CROI) 2023 during her session titled "Advances in HIV Treatment Strategies."

Additional Resource:

• Gandhi M. Advances in HIV treatment strategies. Talk presented at: Conference on Retroviruses and Opportunistic Infections 2023. February 19-22, 2023. https://www.croiconference.org/

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Monica Gandhi, MD, MPH, is a professor of medicine and the associate division chief of the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco (San Francisco, CA). 

TRANSCRIPTION:

Dr Monica Gandhi:

My name is Dr Monica Gandhi. I'm a Professor of Medicine at UCSF and the Director of the UCSF Center for AIDS Research.

This year at CROI, I am going to give an overview talk on advances in HIV treatment for the new investigator session. This talk is actually divided into three parts. The first part is to talk about therapy for treatment-naive patients, the second part is to talk about therapy for treatment-experienced and resistant patients, and the third is to talk about long-acting antiviral therapy.

Now, if we think about treatment for treatment-naive patients, it's pretty much integrase inhibitor-based therapy. So, instead of focusing on the high potency and the high genetic barrier to resistance, which we've all really known by this point, it's why entities are first-line. I'm actually going to talk about data from the meeting on some of the side effects of integrase inhibitor-based therapies. I'm going to discuss weight changes and metabolic changes on INSTI therapy, cardiovascular changes with integrase inhibitor-based therapy, and the advantages of dolutegravir 3TC in terms of switching to that. All of those are going to be bringing in data from CROI.

Then the second part is treatment-experienced and resistant patients. That really is bringing a lot of data that we've had over the last year about what we need to do in very treatment-resistant patients. We have lenacapavir now for treatment-resistant patients. We have fostemsavir, we have maraviroc, we have darunavir, which really is still a mainstay even in patients with a lot of drug resistance. So we'll go over all of that, and then again, some new data from the meeting about high-level resistance to dolutegravir found outside the integrase inhibitor gene.

Then the third part is long-acting antiretroviral therapy. This is pretty much the most exciting thing that's happening in HIV medicine right now. We have one approved therapy for long-acting antiretroviral therapy, which is cabotegravir and rilpivirine, and there is a lot of data at CROI 2023 on this combination. We are going to talk about at this session some work we're doing at Ward 86 of giving long-acting cabotegravir and rilpivirine to patients with adherence challenges. We're going to talk about some of the data that came out of this meeting about weight changes with cabotegravir, and we are going to talk about how potent and exciting this regimen is really, and bringing in some ideas about potential long-acting therapies in the future.

So the advances beyond all that we're going to try to cover in the past and why we are where we are now. The advances, a lot of them are really represented at this exciting meeting, CROI 2023. What we're going to see at this meeting is there's data on lenacapavir and its pharmacokinetics. We're going to talk about that in this talk. There is going to be upcoming data at this meeting about injecting into the thigh with long-acting cabotegravir and rilpivirine. The reason that's important is right now you have to give the cabotegravir and rilpivirine in the gluteal muscle, and actually, that leads to kind of privacy issues. There's no self-administration if you're going into the gluteal muscle. So this data that's going to be presented here at CROIX about good pharmacokinetics when you inject in the thigh is an advance. This actually opens up the possibility of self-administration of these medications of administration out in the field.

Then the third major advance that we're going to talk about in this talk that really is again, bringing in data from CROI, is some of the very exciting data on new formulations of long-acting regimens. There are going to be regimens eventually that are in implant form that are in ways that you can actually give someone an implant and that drug will last for a long time to pair with our currently available long-acting therapy. So, we're going to give kind of a glimpse of the future in this talk as well, bringing in some of the CROI 2023 data.

Really the biggest knowledge gaps at this point are I would say twofold. One is essentially what to do in the setting of high-level resistance. If you have high-level resistance, we've brought in lenacapavir as a new drug for multi-drug-resistant HIV, but what do you pair that with? We are going to talk about what to do in the context of high-level resistance, multi-drug resistant HIV. I do want to mention and will mention in this talk what to think about in the treatment of women who are pregnant because we have a lot of data on women who are pregnant and which antiretroviral therapies to use, and then there are drugs that simply have not been studied in pregnancy. We're using them, but we haven't had enough data in pregnancy. What do we know about the safety of those drugs?

Then the third, I think major point to think about is in the future, what are these novel long-acting regimens that we can get? Right now we're really in the nascent stage of long-acting antiretroviral therapy. We have only one regimen approved, cabotegravir and rilpivirine, both given as individual injections, and then we have a subcutaneous injection approved called lenacapavir capsid inhibitor for multi-drug resistant HIV. That's nascent in terms of the field. What can we pair lenacapavir with? What's coming down the pike? What kind of ideas do we have for long-acting formulations that we can pair with these long-acting formulations that we already have approved or will be paired in the future? It's that kind of aspirational aspect of HIV treatment in the future that we're going to get some data, primate data, pharmacokinetic modeling data from CROI 2023, and we'll bring it into this talk kind of looking into the future. There's nothing more exciting right now in HIV medicine than long-acting antiretroviral therapy.

I think the only other thing to add is that this talk that is really on updates in HIV treatment is meant to be really comprehensive. It is for early-stage investigators, but it's really meant to give a landscape to the field. By the end of the talk, I hope people will see how far we've come in HIV medicine. It is an incredibly exciting time to treat HIV. But one limitation is that we have different regimens available in high-income countries versus low and middle-income countries. Right now the World Health Organization has put cabotegravir as a preventative agent on their guidelines, which will be talked about in the talk after me by Dr. Raphael Landovitz from UCLA, but long-acting cabotegravir and rilpivirine for antiretroviral treatment has not been put on the World Health Organization guidelines for treatment. This creates a two-tiered system where we can use the long-actings that are available in high-income countries and not in low and middle-income countries.

The data from CROI at this meeting and data that's still in progress will hopefully add to our database about using long-acting antiretrovirals for therapy in low and middle-income countries and urge the WHO eventually to approve these formulations on their treatment guidelines