What’s New in HIV Science?

Leading HIV researchers discuss the latest advances

May 29, 2025

amfAR’s new VP and Director of Research Dr. Andrea Gramatica in March conducted a roundtable discussion with three New York City-based HIV researchers: Dr. Marina Caskey, a professor of clinical investigation at the Rockefeller University; and Drs. Brad Jones, associate professor, and Guinevere Lee, assistant professor, at Weill Cornell Medicine.

The following are excerpts from the lively and enlightening discussion, which ranged from the potential and limitations of antibodies in curing HIV to cancer immunotherapy to the persistent gaps in our knowledge of the virus.

Andrea Gramatica: Are there recent advances in HIV research you’re excited about?

Brad Jones: I think it’s becoming clear from interventional studies using antibodies that a greater proportion of people who stop antiretroviral therapy [ART] are able to control their virus than we would expect. Those cases are still fairly rare. But I’m personally pretty convinced that the immune system is learning something in the process of these trials that helps it keep the lid on HIV in a way that it otherwise couldn’t. And that may be through improving T-cell responses or other mechanisms.

And we are fortunate to be able to access samples from Marina’s studies and others around the world and study the T-cell responses and try to figure out how they’re achieving this, and then hopefully move forward to future clinical studies where we can get control in the greater majority of individuals. So that’s one thing I think is exciting.

The other thing that my lab’s been working for a long time is trying to isolate these very rare cells that harbor the HIV reservoir. These are the CD4 T cells that are responsible for viral rebound when people stop ART, and it’s an incredible needle in the haystack problem—they’re present in one in a million cells. But we now have ways to isolate and grow and study these cells in the test tube. And they surprise us every week—we’re always learning something new. It’s the first time we’ve been able to study them in such a direct way. So hopefully that will lead to new ways to understand how to eliminate these cells.

Marina, you’ve been involved for many years in studies involving broadly neutralizing antibodies. What are you currently studying that you’re excited about?

Marina Caskey: Over the course of the infection, there’s a subset of people with HIV whose immune systems, as they interact with the evolving virus, produce these antibodies that are very potent and active against a broad range of HIV strains. These are what we call bNAbs—broadly neutralizing antibodies. Several groups have worked on methods to identify these antibodies and characterize them. And now there are different types of antibodies that are in the clinic that fight HIV from different angles, and they’re being used in different contexts.

It’s reassuring to see that different groups around the world are finding similar outcomes in their studies. At a recent conference, a study in the UK (called RIO) involving men with HIV treated early after infection found that a subset of them went on to control the virus for a long time. Another smaller study in South Africa involved young women treated even earlier and also found similar outcomes.

So now we are at the stage where we are really trying to understand the commonalities and underlying mechanisms so that we can make the outcomes even better in future studies. And then having these tools that Brad’s and other labs have to study the cells that harbor HIV will allow us to find other interventions to combine with antibodies for more successful outcomes.

How is it that these antibodies cannot neutralize the virus?

Caskey: Unfortunately the virus is always a step ahead. So in the person from whom that antibody arose, the virus has escaped. And in fact, we see that in our clinical trials: even though the virus in a person who’s receiving the antibodies may start out as susceptible to those antibodies, it will still find a way to go around the antibody and become resistant. Which is similar to what happened with antiretroviral drugs (ARVs). The same way that combinations of ARVs have improved over time in such a way that now, with the right set of drugs, you’re able to suppress viremia and corner the virus in a way that it can’t escape. We think that we are able to do that with antibodies, too. We just have to identify the right combination for the right person.

Guinevere Lee: I agree. It’s always a tug of war between how fast the virus mutates and how fast the immune system can respond. So when we give a person an antibody or ART, it pressures the virus to mutate in a certain direction, but the virus also mutates at a faster rate than this pressure to “corner” it. It’s always a race between how fast the virus is mutating and how fast our immune system or the regimen we are trying to use as an intervention are able to catch up.

Are there HIV strains that are more prone to enter a latent state or an active replicative stage? What do we know about that?

Lee: That is such an interesting question. We don’t really know. As a virologist I also feel that this is one of the major gaps in our knowledge about the virus because there are a lot of different viral strains circulating in the world. We have subtype B circulating in North America, Europe, and Australia. In Eastern Africa, subtypes A and D. And in southern Africa, subtype C, which is also circulating in India but is somewhat different genetically. And I think one of the major knowledge gaps that we have is to understand the differences between these strains, whether they have different potency or likelihood to become reactivated or establish latency.

Drs. Marina Caskey of the Rockefeller University and Brad Jones of Weill Cornell Medicine (Photo by Colby Tallia)

Are there studies in research areas other than HIV that you find noteworthy?

Caskey: A lot of the cure strategies that we are exploring in HIV are concepts that are being borrowed from cancer immunotherapy. The challenge, however, is that, from a clinical point of view, many of those strategies and drugs come with a lot of toxicities. Unlike cancer patients, people with HIV now live long, healthy lives and the treatments have evolved such that you can live with almost no side effects. But still there are people who would go through a clinical trial of an intervention to not have to take those medications.

The threshold of how much toxicity is ethical is very different in the context of HIV compared to cancer where you’re facing a life or death situation. So how do we transfer that approach to HIV? We have to decrease the dose. We have to give it for a shorter period of time, and then maybe it’s okay. But when we make these adjustments, do we get the same effect that you would need to truly impact the reservoir? So I think that’s one of the challenges we have to deal with.

It’s also true that research on HIV has contributed so much to other fields of research, like cancer. We definitely would not have CAR T cells without HIV research. How do you see this intersection between HIV research and other areas of immunology, virology, etc.?

Jones: One thing I find very intriguing is that in the cancer immunotherapy field, they want to make CAR T cells, which you mentioned, or other T cells that are tough, able to persist, able to divide. These CAR T cells are like living therapies that fight cancer cells. And the HIV reservoir cells are doing kind of what we want the T cells to do to fight cancer. If you think about it, HIV infects many T cells in the body. And then when you start antiretroviral therapy, only the toughest T cells make it out and carry the HIV reservoir 10 years later. So one thing that excites me is if we can study how HIV has kind of hitched a ride on T cells for all those years, so can we elicit those same properties of T cells in immunotherapies for cancer.

Are there studies in research areas other than HIV that you find noteworthy?

And one example of that that came out in Nature a few months ago from Michel Sadelain’s lab. He took an HIV protein called Nef, which the virus uses to help hide those T cells from the immune system. And he gave that Nef protein to the CAR T cells that you mentioned. And he found that with this HIV protein, the CAR T cells persisted better and eliminated tumors to a greater degree. So we borrowed this kind of trick from HIV to make these T cells more persistent.

I think there’s a lot more we can learn by studying these features of HIV-infected cells. It’s really kind of two sides of the coin. We want to know why these infected cells are so persistent so that we can eliminate them. But if we also learn lessons about why they’re so persistent, we can flip that on its head and use those lessons to make CAR T cells and other T cells more persistent.

amfAR’s Dr. Andrea Gramatica and Dr. Guinevere Lee of Weill Cornell Medicine (Photo by Colby Tallia)

So what do you think are the next steps in terms of learning from other fields of research?

Lee: One thing I find really interesting that has been widely adopted in the public health sector is, for example, the flu vaccine. Mutation is always one of the biggest challenges that we face in terms of HIV cure, in terms of vaccine, in terms of therapy. With flu vaccine, we predict what the next set of mutations are going to be next year. So perhaps we can use similar models and/or computational methods, and apply it to HIV evolution to predict the next step the virus is going to take.

The challenge with HIV is that the virus mutates just so much faster than flu—HIV mutates up to 1000 times faster than influenza depending on the studies cited. That’s what we’re dealing with. But I think that’s something we should think about.

What do you think amfAR could or should do to help your research and research on HIV in general?

Lee: Even though we have 30-plus years of research history on HIV, there’s just so much that we still don’t know about HIV, especially because of how fast it mutates. So a focus on basic science and on fundamentally how the virus works, how the immune system and the virus interface with each other is something that is still not well understood.

Caskey: I think investing in early career investigators is a role that amfAR can continue to play. Sometimes one needs just a foot in the door and it’s hard to get that foot in the door now, and it has been this way for a while. So it can really make a huge difference for someone who’s at the very beginning of their careers.

Jones: That’s a nice segue for me to say that my first grant ever was from amfAR. I’ve had a number of amfAR grants over the years, and I think one of the other things I would mention is the ability to bring people together in different fields. I was awarded a different amfAR grant called a magnet grant, which was for one year of funding to engage with data scientists and bioinformaticians. That was several years ago and we’re still working with those folks.

But it’s not always that easy. I’ve tried to attend cancer immunotherapy conferences and thought I’d just absorb this information and come with up with ideas, but it’s hard. It takes time and effort, and you really need people to connect with each other, either faculty or maybe even better if you have postdocs connecting with each other because they’re the ones who bring a lot of energy and drive to the projects they’re working on.

Caskey: And even within HIV, you would be surprised at how the HIV vaccine field does not really interact much with the HIV cure field. So you have to cross the aisle, so to speak, even within the greater HIV field.

Landing page photo of Marina Caskey by Mario Morgado/The Rockefeller University

Click Here to read more from the May 2025 issue of amfAR INNOVATIONS.