The 10th IAS Conference on HIV Science (IAS 2019) featured plenty of discussion about the current direction and future prospects for HIV cure research. One such discussion was a media roundtable entitled "Cure Research: Where do we go from here?" that featured some of the most prominent names in the field, including Steven Deeks, M.D., a professor of medicine at the University of California-San Francisco. Deeks, who is also a principle investigator at the amfAR Institute for HIV Cure Research, spoke with our correspondent Terri Wilder after the roundtable.
Terri Wilder: I know that you've had a lot of things going on at the conference. But one of the things that kicked off the conference is that you were the co-chair of the HIV/hepatitis B symposium that took place as a preconference. Can you talk about some of the key highlights for you, that you think our readers should know about?
Steven Deeks: Hepatitis B is very common across the world. The number of people who are dying from hepatitis B on a daily basis is actually a bit more than HIV. Both hepatitis B and HIV have the same fundamental problem. We can give people antiretroviral drugs that block the virus, but we can't cure anyone.
So with HIV and hepatitis B you have to take drugs for life. With both issues, there's a tremendous amount of stigma. Both hepatitis B and HIV tend to sort of gravitate to the marginalized people in society. And so the epidemiology in the big-picture perspectives is remarkably similar.
But biologically, in terms of cure, which both fields want, it's quite similar. We have the latent reservoir; this integrated HIV DNA that's in these cells that we can't get out. And they have something called ccDNA, which sort of acts in the same way.
So both fields are more or less at the same spot, in terms of trying to come up with novel therapies, most of them immune therapies, to enhance the capacity of the immune system to kill the infected cell. And the studies that they're doing in hepatitis B look remarkably similar to the studies we're doing in HIV.
So there's a fair amount of enthusiasm. There are some differences, but the differences didn't seem as remarkable as the similarities.
TW: I just want to ask about funding, because you were just on a panel with a representative from the National Institutes of Health -- they fund cure research, Pharma funds it, some of the foundations, amfAR. What does the funding look like, if you compared HIV to hepatitis B cure research?
SD: An interesting discussion occurred at the meeting. There is, who knows? Ten-, twenty-, a hundredfold more funding available for HIV research from the foundations and the governments, particularly NIH, than there is for hepatitis B. And that's actually in part because, from a public health perspective, we have a vaccine for hepatitis B. So, a lot of the work we're doing in HIV is to develop a vaccine for HIV. So they've done half their job.
But the interesting thing at the meeting that came up is that, yes, the HIV people are blessed by all this funding for basic science. But industry doesn't really want to engage with us.
Hep B has the opposite situation. They don't have any funding for the basic science, but they have a massive amount of companies who want to work with these clinical teams, in particular, to test new ideas in the clinic to see if they can cure things. So there's a huge industry around curing hepatitis B, but not HIV.
TW: Why do you think that is?
SD: The answer there is pretty straightforward. Many people who get hepatitis B clear it on their own. Not clear; but they basically have a functional cure on their own. Ninety-some percent. And that doesn't happen in people with HIV. So it seems biologically, and therefore therapeutically, to be a lot easier to cure hepatitis B than HIV.
TW: Earlier you were talking about the three areas of HIV cure research that are kind of questions that people are asking, like: Why does the virus persist? When people are in treatment, why doesn't [the medicine] just get rid of it? How do we measure the virus?
Can you talk a little bit about those questions, and why they may be stumbling blocks for us?
SD: All right. So, the first question is: Why does HIV persist? And the antiretroviral drugs are very powerful and potent. And [with antiretroviral therapy] you get rid of 99% of the virus within weeks. But 1% of the virus sticks around. Now, why is that?
Well, we always knew about this latent reservoir, but what does that even mean? What we've learned over the past year or so is that a virus will infect the cell. That cell, under treatment, will then divide, and divide, and divide. Billions of cycles of division in some of these models. And so one infected cell becomes this massive population of cells 10 years down the line.
So we've got to learn how to stop that process -- what we call clonal proliferation. That's the most important discovery that we've made, in terms of the why question.
The second question I asked is how to measure this stuff. Right? If you want to do a clinical trial, you've got to measure something. The reason why we have 30 or so antiretroviral drugs is it became very easy to measure the viral load. That allowed companies to just pour in. They measure the viral load. They find a drug.
See if the viral load goes down. Boom! They've got a drug. They get it approved. Doesn't go down? Boom! They stop. So we need a biomarker, a measurement, of the reservoir that will allow us to do these clinical studies, but really, to allow the companies to start testing ideas.
And there's been some progress there. There are newer assays. They're not perfect. But there are probably some new initiatives that are going to be built to sort of try to figure this one out.
TW: Somebody brought up the question that people are uncomfortable answering, which is about timeline in terms of cure. And you said that you think probably in three to five years we might have a combo regimen that perhaps could move to proof of concept.
SD: Right. I mean, that's all you can do right now. You can predict, based on what is in the field, well, if there's these 12 or 15 ideas in the field and a couple work, and that takes two or three years to figure out, then you can imagine how they would be combined. And based on what we know in the monkeys, if you took a drug from Class A, and a drug from Class B, and a drug from Class C, and you put them together in the right way, it might work. Probably not. But we'll at least begin to test that idea in five years -- which is not the same as having a cure in five years. It's having something that's testable.
TW: When you think about cure research, which -- I know you've been doing this for a while -- what is most exciting to you, in terms of what you think is happening next, or what's happening currently?
SD: Well, HIV is always full of surprises. The thing that's happening with HIV that is exciting is that we have a population of people with HIV that are really engaged in these studies. Altruism, OK? We have these great questions, which everyone wants to answer: Can you cure the virus? And we have resources.
And over the past 20 to 30 years, because of all the money, I think, the HIV field has recruited some of the smartest scientists in the world.
So you have a clever virus that's always coming up with new tricks. You've got a highly engaged funding cycle. You've got very smart scientists. You've got the patient population. So you have this capacity -- which I think is unique to HIV, and particularly to HIV cure -- to do science in people in a meaningful way. And that's, to me, an honor that I'm able to do that. Because I honestly don't think that happens in any other medicine; that all of that stuff has come together.
So you go to work and you have great people in your studies, and you have great collaborators, and you have all these ideas, and you're trying to do something important. And you know, nine out of 10 times what you do doesn't work. But sometimes it does. That's great. And even when it doesn't work, you get new ideas.
So that's science. It's a good time to be doing HIV science, particularly in the cure area.
TW: Can you talk a little bit more about the altruism of the patient population? You're in San Francisco. There's a very long history of the HIV social movement, the patient self-empowerment movement. Where do the people who are living with HIV, that are maybe long-term survivors, that are coming to you, that want to be part of these trials -- how do they influence what you do, and what you think is going to happen in the future?
SD: Well, that's a great question. So, in San Francisco we have a population of men now who, 20 years ago, thought they had a death sentence and saw all their friends and lovers die. And then they did not die. They were put on toxic regimens, and then they were struggling with all these terrible regimens we had back in the day. And it took the next 10, 15 years to sort of fix all that.
And now they're well. They're also now retiring, and older. And you sort of get a sense that a lot of people are thinking back on what happened, how come they survived, and their lovers and their friends did not? And what can I do now to sort of give back? Which I think is common at some point in life.
And you've got this generation of men who haven't forgotten, and who I think will get general satisfaction, in a very sincere way, by actually coming into these studies and doing things which are often quite uncomfortable, time consuming, and have zero chance of helping them -- in fact, often have a significant chance of hurting them. And they're doing it, not for the money, or not because they're bored, but because of this genuine sense of altruism -- which can be inspiring.
TW: You talk specifically about men coming. What do you think it would take for other communities to be more part of this cure agenda? What would have to take place?
SD: Yeah, yeah. So the altruism side is different, particularly in women. There wasn't a massive holocaust of women like there was of gay men. And the epidemic was much more diffuse, and was slow to take off, and it happened mainly in the treatment era. So what would motivate women would be something completely different. And we need to understand that. What will motivate a woman to enter a study?
Because we're used to what motivates men, and particularly for HIV studies. But that's not going to motivate women. So women need to have a reason to do this. And it's very important, because a woman with HIV -- that comes with lots of other stuff, almost by definition. They often have hepatitis B; they [often] have hepatitis C. They acquired HIV [usually] either through sex work or through IV drug abuse. The sex work, that comes with socioeconomic issues that have to be addressed. Poverty, in particular. Violence in their life. If it's IV drug abuse, you know, is that active? Did it destroy their veins?
A woman who gets HIV typically has all this other stuff going on, which makes them -- you know, if you take your standard clinical trial protocol that you get from an industry or from a network, you look at these things; you know, they can't have hepatitis C; they have to have good veins; they can't be using any substance abuse things. Boom, boom, boom. They can't have any mental health disease. They have to be housed. They have to be dependable. They have to take their drugs every day.
If that's what you want, you're not going to get the typical woman with HIV -- at least, in my area. So you've got to design. You've got to figure out what it is that women want out of these studies. How can you help them with the logistics, childcare; and how can you design a study that's consistent with who they are, not the kind of studies that we do now?
TW: Thinking outside of San Francisco, United States, how are we going to start engaging people around the world, internationally? I mean, one of the things that I think you said earlier was, we may have to think about moving cure research out of an academic setting.
SD: I don't know what will motivate people in an African setting. But what I do know is that we're not going to do any really high-quality research until we build the infrastructure to do these types of studies.
Right now in Africa they're doing all these great antibody studies. But they're typically larger, phase II studies. But right now, when you're doing HIV cure studies, you need to do leukapheresis; you need to get tissue; you need to interrupt therapy, which is often -- which the regulatory groups down here, or in Africa, typically are going to say, "No way." So there's all the regulatory stuff. The capacity to get tissue stuff -- all that requires building pretty intense resources and infrastructures. They do exist. I mean, everything that I can do in San Francisco, you can do in Durban [South Africa] now.
But we need to build more of those centers. And then, once those centers are there, then you can bring in all the various ideas that we have in the North and just start doing it there. And I bet it would roll much quicker, and we'll get data that's much more relevant. We'll have girls and boys, men and women, children and adults. That's how we're going to get the diversity that we need.
TW: Can you close by saying a little bit about what you're working on right now?
SD: The big one that we have coming up, with support of amfAR, is a study in which we're combining a vaccine, a vaccine adjuvant, antibodies. It's one of the first studies I think that have been designed, not to just do experiments in people, but to actually see if it works.
That study has been in development for quite some time. Hopefully, in the next few months, we'll start it up. Give us a couple years, and we'll have an answer.