In a far ranging interview at the International AIDS Society Conference in Sydney, Australia, Peter Staley talks with Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, about his research on HIV “eradication,” President Bush’s AIDS legacy, why he likes gay men and Republicans, and that letter he wrote supporting Scooter Libby. Below is the transcript. To see the video click here.
I’m Peter Staley with AIDSmeds.com, and we’re here with Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, the institute that funds and does the bulk of the AIDS research for the U.S. government.
Thanks for joining us, Tony.
It’s good to be here, Peter.
Peter Staley: You’re giving one of the keynote speeches at tonight’s opening ceremonies, and you’ve titled it “HIV/AIDS in 2007: Much Accomplished, Much to Do.” Can you give us a preview, or an abridged version of the main points you’ll be making tonight?
Tony Fauci: Sure, I picked that title, Peter, because I was reflecting back, in fact, eleven years ago, in 1996, when, following the meeting in Vancouver when we had just begun to see the results of the triple combination of therapy and we were seeing so much dramatic response in people that there was a lot of optimism and almost euphoria about what was going on. And the Journal of the American Medical Association asked me to write a commentary to balance that, and say what have we accomplished in reality but what are some of the challenges? And I did that in that commentary and now 11 years later with many, many more advances that we have, when the organizers asked me to talk about the subject of my choice, I harkened back to the title of “Much Accomplished, Much To Do.” So what I’m going to be doing tonight at the Opening Ceremony is I am going to be talking about, within the context of what we’ve done, what impact it has and what we really still need to do in the three major areas of pathogenesis treatment and prevention. So if you take pathogenesis for example and you look historically—that has served as the basis for much of the decisions and the advances that we’ve made in treatment and prevention—is understanding how the virus works. Probably the classic example of that which I’m going to show is understanding in detail the vulnerable points and the replication cycle of the virus which has allowed us to target, for example, reverse transcriptase, protease, and now, most recently, integrase, also diffusion and binding inhibitors. So that’s a great deal that has been accomplished.
What needs to be accomplished in pathogenesis? Well, we’re starting now over the last two years to realize the importance of early events—from the time an individual gets infected and the virus seeds—we know now that the gut-associated lymphoid tissue is critical to those early events. So you can get damage to the immune system, particularly your memory pool of cells, very, very early on which re-resurrects the question of should we be treating people earlier to prevent that. And what could a vaccine, even if it doesn’t prevent infection, what could it do by blunting those early catastrophic destructive events that occur in the gut-associated lymphoid tissue. So a lot has been done in pathogenesis but pathogenesis is informing us of a lot more that needs to be done.
The second issue that I’m going to talk about is treatment, probably the most important component of AIDS research with regards to results that are tangible. We’ve made spectacular strides with the development of so many drugs that have had such important impact. So what are the challenges? What must we do? We need a continued pipeline of drugs. And in this meeting you’re going to hear discussion of the integrase inhibitors, of the maturation inhibitors, of the fusion inhibitors. Those are very important things that we need to do.
What about access of therapy? We’ve been very successful over the last 3 or 4 years in getting drug to the developing world. Say two or three years ago there were about 100,000 people at most who were on therapy, now more than 2.2 million people, mostly through the PEPFAR program and the Global Fund as well as the Gates and the Clinton Foundations. But what are the challenges that need to be done? If you look at the numbers, even though they’re exciting in what we’ve done, they’re somewhat sobering. Only 28% of the people who really do need therapy, particularly in the developing world, are actually receiving it. And if you do the math that for every one person you put on therapy, six new people get infected, the math is telling us that treatment alone is not the answer.
Which brings us to the final part of my discussion, which is prevention. We’ve made great strides in prevention of sexually transmitted, blood transmitted and mother to child transmission. Even though that’s the case, if you go and examine carefully the accessibility of those proven preventive measures to people throughout the world it’s really shocking. Less than 10 and 20 percent in almost all of them—from access to condoms to access to behavioral changes to access to treatment of mother to child transmission—we need to do much better than that. So the challenge is really pretty daunting on that.
And then finally the issue of a vaccine, which is the last great scientific challenge, and there is much to do in that. We are starting to see we may need to accept, at least initially, somewhat of a modified paradigm of vaccine—mainly a vaccine that doesn’t necessarily prevent infection but that blocks the progression of disease, keeps the viral burst and set point low enough to have the secondary effect of preventing transmission to other individuals.
So going through that list of the three major components, there indeed is much to celebrate but there is an incredible amount to do. And I close by saying something that I feel sincerely. That whenever you come to a meeting and people talk about all the great accomplishments, particularly over the last 26 years from the day we first knew we were dealing with a new disease, as a global society we’re really going to be judged as much by what we do in the coming years than what we accomplished so greatly in the previous years. That essentially is my talk.
We’re going to get back to PEPFAR and discussion of vaccine. First, NIAID had some pretty amazing news this year. One of your researchers, Dr. Tae-Wook Chun, is a lead author of a study that you co-authored looking at the life span of so-called viral reservoirs in the body, and, correct if I’m wrong here, you made the bold claim that if someone started taking HAART soon after they were infected, they could potentially eliminate their viral reservoir within 7.7 years. Can you explain this in laymen’s terms?
Yeah, I think in laymen terms it was probably not said precisely enough that made it a little bit somewhat misinterpreted. What I was saying is that we studied for years assiduously people who had been on therapy who started their therapy years after they were infected. Two things happened to those people: They have a pretty substantial reservoir. So that even when they come in with antiretroviral therapy and suppress the viral load to below detectable levels, the reservoir is substantial. Its decay is a curve that doesn’t look like it’s going to disseminate and dissipate itself for a very long period of time. In addition, the immune system of those patients is damaged so much from the years of having active viremia and virus circulating that even if you did get down to a low reservoir, the immune system probably would not be able to be able to prevent the rebound after you stopped therapy. And we know that ourselves because we did the study where we looked at people who looked like they were having phenomenal control of their virus with a small reservoir, they stopped therapy and the virus came back.
What’s different about the study that we did this past year in the Journal of Infectious Diseases? We followed for over eight years people who had started literally within a few months of the time they were infected. And we waited eight years to go out and take a look at their viral reservoir. And we found two things that were striking. First of all, the viral reservoir was vanishing small—much smaller than we had seen in the people whose therapy was started when they were essentially viremic for years. The other thing is that the curve of the decline was much steeper suggesting that there is a possibility that you may get that viral reservoir so low—and I hesitate to use the word eradicate, Peter, because that’s a word that gets you into trouble.
It’s loaded…it’s cure.
It’s loaded. It really is a loaded word and you don’t want to talk about that right now because that’s not something that we have scientific evidence that we can do. But what we do have more accumulating scientific evidence is that if we can get that viral reservoir so low within a template of individuals who still have preserved HIV-specific immune function, it is conceivable, and that’s really the message, not eradication, but the message is that it’s conceivable that with those individuals when you ultimately stop therapy that the actual residual immune response that you have will contain the virus so that you don’t have to go back and give those people therapy—they won’t rebound. Making them, essentially, similar to the elite long-term non-progressives—people who you can demonstrate they have the virus but for one reason or another they don’t require treatment. That’s the goal.
But there was an accompanying editorial in the journal from Margolis and Nancy Archin of the
I respond that we were the ones that proved that that’s the case. I mean, we were the ones that did the study years ago—that got the viral burden low and the reservoir low. And we stopped therapy and it bounced right back. So we’re not talking about eradication. I agree—eradication is something that very likely will not occur. The point we were making is that this study is a little bit different than the study that we did, in fact, a lot different. The one that we did years ago in which people were studied who were on therapy only after having had viremia for years. There’s a difference when you get people very early. Does that mean we’re going to eradicate it? Unlikely. But does that mean we have a better chance of the body’s residual immune response controlling that virus—I think there is a reasonable chance that that’s the case.
Let’s talk about PEPFAR. You and I had a long discussion about it in Toronto.
We’ve had a lot of discussions about it, right?
We just heard from President Bush about PEPFAR 2, which is basically a doubling of the amount of money spent during the first five years. And, for our audience, PEPFAR is the President’s Emergency Plan for AIDS Relief. It’s his international AIDS program for treatment and prevention. This was billed as a doubling of his previous commitment—the $15 billion proposed for its first 5 years, from 2004 to 2008. By any measure, it’s obvious that President Bush has done more on international AIDS than his predecessors. However, some AIDS activists claimed that the announcement was more hype than hope. For instance, PEPFAR’s first five years of spending had a very steep spending curve. It started at about 2 billion in its first year and will end at about 5 ½ billion in 2008. Since we’re almost at $6 billion a year, activists claim that PEPFAR 2 is basically an announcement of flat funding from here on out. Does the President assume there’ll be no need to increase PEPFAR funding each year over the next five years?
Well actually, I think it’s important to point out, Peter, that there are two levels of what we would call victory for PEPFAR here. The first is the anxiety of whether or not it was going to be renewed. Which many of us, myself right at the top of the list, were absolutely adamant that we had to renew PEPFAR. So the very fact that it was renewed for an authorization for an additional five years is a big plus. The point you make is a reasonable point, but really what it reflects is that the originally PEPFAR 1 went beyond what it was originally planned to do because you remember you and I had the conversations in the first year or two of PEPFAR that it was supposed to be $15 billion over five years equal to $3 billion a year. So in the first year or two when it was not quite three people were saying, “Oh, you’re going to underfund it—you’re not going to meet it.” And then when you get to the fifth year, you had almost twice as much in the fifth year as what the average would have been. So the $15 billion program actually turned out to be something like an 18 or 20 billion dollar program.
Eighteen.
Eighteen and change actually.
But wasn’t Congress the driving force for that overshooting of the 15 billion?
Actually, it was in the President’s budget with some modest changes by Congress. So when the President comes and says we’re going to make it thirty, you’re absolutely correct. It isn’t that the second part is going to totally double what the first part is because the first part turned out to be more than what was originally intended. So when I look at, in my way, who is always a cautious optimist, is that A) we wanted to nail it down that it got renewed and it’s renewed. Good news. B) Do I want it to be and think it likely will be more than 30 billion? I think when we get out five years past the 2008 that the cry and the need for more treatment and prevention will move whatever administration and/or Congress is in power in the United States to give more money. So I look at thirty billion as the floor, not the ceiling, of PEPFAR 2.
But Bush won’t even be in office for most of this. Why didn’t he announce a program that would call for annual increases because obviously we’re going to have increased need over time?
You know, I can’t answer what went in the mind of the president except to tell you that it is our hope, and I think it’s a reasonable hope, that we got over the first barrier—it was renewed. A successful program was renewed. It was renewed at more than what the original one was and even more than what the original turned out to be. It shouldn’t be interpreted that over the next five years we’re going to double the amount that we did in the last year of PEPFAR 1. It will double the amount that was originally—it doesn’t come out in real dollars to be double what was in the last year. So I hope as we get to the second, third, fourth and fifth year of PEPFAR 2 we’re going to follow the same trajectory as we did in PEPFAR 1. That at the end of that five-year period there’ll be more than 30 billion dollars. I hope it is the case and I think it will be.
What about the goals though? The stated goal of PEPFAR 1 was to treat 2 million people by the end of the five years—it missed that goal substantially. 1.1…
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