February 17, 2010
Below is the transcript of a press conference held at CROI 2010 on Feb. 16, featuring Anthony Fauci, M.D., Director of the U.S. National Institute of Allergy and Infectious Diseases.
Anthony Fauci: It's a pleasure to be here this afternoon. I'm going to talk later on in the day. The title of the talk is "The HIV/AIDS Research Agenda: A View From NIAID."1 And what I've elected to do is rather than go through a very detailed research agenda of everything that we'd be planning to do through our grantees and contractors, I've picked three issues that I consider bold -- high risk, but high return -- that we are going to be pushing the envelope on, under the larger rubric of the common goal that we all have here at this meeting, to control and ultimately end the HIV/AIDS pandemic. I'm not going to talk a lot about pathogenesis at all -- not that I don't think that's very important, because actually that's what I do in my other hat of a scientist. But I'm going to talk about three issues.
Anthony Fauci, M.D.
The first is to aggressively seek, test and treat infected individuals. The second is the issue of the possibility of curing at least a proportion -- I don't know how large that proportion would be, or when it would occur -- of HIV-infected individuals. And lastly, but overwhelmingly importantly, is preventing new HIV infections.
With regard to the first, aggressively seek, test and treat, the reason to do that is very clear. We have spectacularly good results for treatment of HIV-infected individuals to the people that we can access. However, if you look at the numbers and do the math of the number of people that are treated and those who have access to treatment, particularly with the new guidelines of getting even more people in treatment, treatment alone in a vacuum is not the paradigm that's going to get our arms around HIV.
So you have to go to two other things. You've either got to be able to get people on therapy or you have to prevent new infections. And if you look at the cure -- again, I'm not going to go into any detail; I'll be happy to answer any questions about that -- that is a high risk, but incredibly high-impact endeavor. We would have never have thought that we would have had any drug against the retroviral infection 28 years ago, when I first started seeing patients at the NIH [U.S. National Institutes of Health] clinic in the summer of 1981. And now we have 30 that in combination bring the viral load down to practically nothing, certainly undetectable in a large proportion of people. So that's the cure.
The next is prevention. I've divided prevention into two parts, [and one is] antiretrovirals as prevention. And there are several ways we're going to be talking about that this afternoon/evening. One is microbicides with antiretrovirals in it. One of the young fellows asked a question of Susan Buchbinder about whether microbicides without ARVs [antiretrovirals] in it is a dead issue. I wouldn't say it's a dead issue, but it's on a respirator and it has "Do Not Resuscitate" tagged on it. I think what we're going to have to do is clearly go with ARV. And if somebody comes up with a great idea that doesn't have an ARV in it, we'll certainly look at it carefully and peer-review it. But I really do think that our experience over the last several years is that we've got to go with ARVs in microbicides.
The next is PrEP [pre-exposure prophylaxis], which was explained beautifully both by Susan and by Scott Hammer. A very important issue. The question is, is it going to be feasible? And the other is "test and treat," which you heard both from Kevin [De Cock] as well as from Scott. And that's an issue that really requires feasibility studies. And I think the research there is, can it be done? One of the points I want to make is that we shouldn't make the perfect be the enemy of the good, in the sense that if we don't go by the model of 95% of this and 96% of that, I still think the concept of treatment as prevention is very, very promising. We've seen data at the community level by Julio Montaner and others. I think it's something we need to pursue -- I know we're going to pursue, because we are going to pursue it.
And the last is a vaccine. I'm going to review for you the history of vaccinology, very briefly, where we are now, post-Thai trial, dividing it up into two issues. One is, what are we going to learn from the Thai trial and where do we go from there? As well as some of the fundamental issues and questions of vaccinology, which were brought up beautifully by Julie Overbaugh and others. So I'm going to try and put that at a 30,000 to 40,000-foot perspective in 25 minutes.
[question asked off-mic; John Mellors, who moderated this discussion, rephrased it into a microphone]
John Mellors: What do you think is the reason the Thai trials showed a signal in the right direction?
Dr. Anthony Fauci: First of all, we don't know. That's part of the post-Thai research agenda. But importantly, we know what it isn't. And that's why I find that trial, even though the percentage was relatively low, 31%, barely significant, it tells us that you can prevent acquisition with something that is not the classical neutralizing antibody. Relates very interestingly to what Julie was saying when she was looking at whether neutralizing antibodies actually can block acquisition in a model other than a sort of a pre-prepared primate model. The answer is, we don't know. We hope it's an antibody, but it may be something else. We're not sure. Hopefully, we'll be able to find that correlative immunity. If we do, I'm going to be very happy and so are a lot of other researchers in the field.
[inaudible question about how to successfully implement a "seek, test and treat" strategy]
Anthony Fauci: How should we do it? Well, we delineated that -- for those of you who want to get the details of it -- in a JAMA [The Journal Of the American Medical Association] commentary that we wrote, a short while ago, Carl Dieffenbach and I, but fundamentally they're all feasibility studies. We're going to be doing a study, which I'll mention in my talk very briefly, in sister cities. We're going to be doing it in Washington, D.C. And we're going to be doing it in the South Bronx. And it's very interesting. Before you can get to test and treat being something that works, you've got to find out is it feasible to test everyone in a particular community. If you do testable, is it feasible to get them on therapy? If you therapy available, will they take the therapy? And then all the questions that Kevin and others asked. What about resistance? What about behavioral disinhibition? What about cost to the individual versus society? What about the ethical considerations? So it's a research agenda that has multiple components to it. So there are a lot of important operational-type research questions, which we are going to pursue.
John Mellors: Let me repeat that: What's changed to increase enthusiasm for the cure research agenda?
Anthony Fauci: Well, what's changed is the realization that as good as we get with keeping people alive for decades, there is a persistent reservoir, that my lab and several other labs have studied, that doesn't disappear no matter what you do with the currently available drugs. The currently available drugs are fantastic for keeping people well and infected. What we're trying to do right now is saying, why not -- I mean there's a whole list of possible chemical molecular activation concepts that are going to be pursued. Doug Richman and colleagues outlined that very nicely in a Science article, a short while ago. So what it really is is setting a high bar for ourselves, that there are ways that we know people can be well with a residual, small reservoir.
We tried things that I'll very briefly mention. Starting people as early as you can possibly treat them. We have some patients that we've collaborated with the Canadians on that within a couple of weeks to a month of the time that they were sure was their exposure, we started them on aggressive modern-day triple and sometimes quadruple combination. And we followed them for a very, very long period of time. And even when we couldn't find the virus by PCR [polymerase chain reaction], which we -- you know, you can always find the virus by PCR, we know that when you stop therapy in them, it comes back. So we really have to go after that reservoir. And it was as several speakers have said, that's really the challenge. So that's really changed. The realization that pushing and pushing and pushing with the current therapy is not going to get us there.
[inaudible question about whether, due to limited available funding for NIAID, Dr. Fauci is suggesting there will be less of a focus on some of the emerging issues facing HIV-infected patients, such as bone disorders, inflammation, cardiovascular disease, etc.]
John Mellors: So the question is, with limited resources, how do you prioritize?
Anthony Fauci: Well, you just do that. You prioritize and it doesn't necessarily, though it's obvious, your question is very meritorious because that's the first thing that comes to your mind. You have a limited number of money. You want to do these things. What are you going to not do? When you look at any portfolio, you don't say, "We're not going to study aging in HIV." What you do is that you're going to have to fund the most highest ranking priority grants within an area. So we don't cut areas out. It's just that we're not going to have the luxury to go down and fund 25 people in a certain area. We may be able to fund 15 or 12 and then have the others go to something new that we want to do. There's not going to be massive shifting of money. We've been doing that for some time now. Everybody is struck with the fact that we have a flat budget this year. Guess what? We've had a flat budget for six and a half years.
John Mellors: I can't help but ask this question with the two guys to my left [Eric Goosby and Anthony Fauci] here. So there are effective means to block transmission. There are technological fixes that we already have at our disposal. But the penetrants to the people, the populations at risk, is less than one in five. Who's responsible for improving that and basically how do we get there? What is PEPFAR's [U.S. President's Emergency Plan for AIDS Relief] role? What is NIH's role? What is any agency's role?
Anthony Fauci: That's a great question. My good buddy of 28 years here [pats Eric Goosby on the arm], we've discussing that for a long time. I refer to it at a recent talk I gave as, you know, you talk about the credibility gap and the resource gap, I call this the responsibility gap. It really is. I mean it's a responsibility gap because the NIH with their research agenda is mandated to do this. PEPFAR with their treatment, prevention and care agenda is mandated to do that. I think we both realize now, as well as others, we're certainly not the only two players in the field, realize that there is an enormous gap there of operational, implementation type of research. Why when we have -- I'm going to show a slide that several people showed -- 12, 13 research-proven prevention modalities and 20% of the world who could benefit from them have access to them? I mean we've got to find out exactly what you're asking, John. Why is it that they're either not getting it or when they're getting it, they're not abiding by it? And that's a research question. You can call it operational. You can call it whatever you want, but we're working together to get that answer.
John Mellors: Ambassador, do you have any thoughts on that?
Eric Goosby: Thanks, John. It is a terrific question and I think Tony answered it really nicely. From a PEPFAR perspective, we are realizing the mandate need to scale prevention like we scaled treatment. We are no longer in a position where we have the cover, if I could use that word, to not engage in strategies that we know are effective and that need to moved from pilot to scale. We are committed over the next two years to do just that in most of our focus countries in PEPFAR. And I think you're right to challenge us on it.
This transcript has been lightly edited for clarity.