Eli Y. Adashi, MD: Hello. I am Eli Adashi, Professor of Medical Science at Brown University and host of Medscape One-on-One. Joining me today is Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH [National Institutes of Health]. The recipient of many honors, Dr. Fauci has been at the forefront of this nation's struggles with infectious diseases for close to 30 years. Today's conversation marks 30 years since the emergence of the HIV/AIDS pandemic, surely one of history's worst. Welcome.
Anthony S. Fauci, MD: It's good to be here.
Dr. Adashi: What actually happened on June 5, 1981, the historic and perhaps transforming event, which we are recognizing today?
Dr. Fauci: I can remember very specifically how this event affected me. I was sitting in my office at the NIH when the Morbidity and Mortality Weekly Report of June 5, 1981 was on my desk, and I picked it up and there was this report that made me very curious. I had been an infectious disease-trained person and had been doing infectious disease and immunology for the previous 10 years. I read this report of 5 men, curiously all gay, and all previously otherwise healthy, who presented in Los Angeles with Pneumocystis carinii pneumonia, and I said "Wow, that's unusual." It was an opportunistic infection that I saw not infrequently because when I would do infectious disease consults for the National Cancer Institute, patients who were getting chemotherapy for their cancer would occasionally develop this as an opportunistic infection, particularly those who were on glucocorticoids. So I looked at it and I said, "Gee, this is an oddity," and I kind of put it in the back of my mind as a curiosity that might just disappear and we'll never hear about it again.
But then about a month later on the fourth of July in 1981, the second Morbidity and Mortality Weekly Report came out, now showing an additional 26 men, again curiously all gay, otherwise previously healthy, who not only had Pneumocystis pneumonia but other infections and an unusual form of cancer called Kaposi sarcoma. They were not only from LA but some from San Francisco and New York City.
It was really at that point, as a physician-scientist, for one of the first times in my professional career, that I actually got goose pimples looking at something because I didn't know what it was. But I knew it was something new because I had been doing infectious disease for the previous 10 years. I hadn't seen anything like this, and I made a decision at that point in my career to turn around from what I was doing and to start pursuing this mysterious disease.
With those 2 reports began the era of HIV/AIDS. We didn't yet know it was HIV, we weren't calling it AIDS, we knew that it was mysterious and we had no idea what caused it, and then from there unfolded historic events over the next 3 decades.
Dr. Adashi: It now appears in retrospect that the story begins long before 1981 when a predecessor of the HIV type I virus crossed the species barrier from a chimpanzee to a human.
Dr. Fauci: Right.
Dr. Adashi: How often does a disease make itself known that way? How often do we acquire new diseases through such transspecies migration?
Dr. Fauci: Well, much to the surprise of most people, quite frequently. Let me explain. We get emerging and re-emerging diseases and new diseases all the time. I mean, literally, when I testify before the Congress I'm always telling them each year about a new disease here or there. About 70% of the newly emerging infections are zoonotic in the fact that they jump from an animal species to a human. The issue is that not all of them have a major public health impact. [One example of a disease that does that] frequently is influenza. Typical examples include bird flu, swine flu, etc., but most of the things that jump species are curiosities that affect a relatively small number of people. They give us pause to think but don't have a major impact on global health.
Every once in a while one of these emerging microbes not only jumps species but it explodes through the population the way HIV/AIDS did. We didn't know that was going to happen in the summer of 1981, but there were several of us who were looking at this and saying, "Now wait a minute, this is certainly a sexually transmitted infection," even though we didn't know what it was. One of the most universal things in the human species is sexuality, so we better be careful about whether this is going to stay confined.
In fact, I remember the other day I pulled out an article that I wrote in December of 1981 that was published in The Annals of Internal Medicine in 1982 that said anyone who thinks that this is going to stay restricted epidemiologically to a small group of individuals (because at that time it was only reported in gay men) is making an assumption that is based on no scientific information because we don't know where this is going to go. Unfortunately, that caveat turned out to be true.
Dr. Adashi: Yes. So that foresight was accurate and we now know that perhaps over 60 million men and women have been infected since the epidemic began.
Dr. Fauci: Right.
Dr. Adashi: As we speak, about 33 million individuals worldwide live with the disease, about 2.6 million men and women are infected annually, and there is no obvious end in sight although there is some good news, which we hopefully will get to before too long.
Where do you see this going, from the perspective of someone who now has 30 years of insight?
Dr. Fauci: I think we are really at a turning point -- a potential turning point and hopefully a real turning point. Let me explain what I mean. We've known since the mid 1990s (in 1996 the protease inhibitors were approved) and we had the first real "cocktail" or "triple combination" or HAART, however you want to refer to it, but from that time on, with new and better drugs and a more user friendly approach -- first 25 pills, then 3 pills, then 1 pill -- we have had a major impact on treating people who are HIV infected.
At this anniversary time, I began to think back to when I was admitting patients to the NIH Clinical Center in the early 1980s before we even had AZT. People would come in to the hospital with advanced disease and the median survival was 28-29 weeks. It is not like today where you can get a serologic test that can tell you you were infected a month ago or 6 weeks ago. Now if a young person comes in to our clinic who was recently infected and is, let's say, 20 years old and you put him on appropriate therapy, you could mathematically model that that person will live an additional 50 years!
The advances in treatment have been stunning. We've had a number of advances in prevention but the math of it tells us that we have a problem and now we're hopefully getting closer to a solution. If you look at the infections worldwide, 90% plus are in the developing world and 67% are in Sub-Saharan Africa. For every 1 person that we put on therapy in lower and middle income countries, 2.5 (2 to 3) people get newly infected. So critical right now is prevention.
So you ask me where are we now and where are we going? We now have a number of prevention modalities that have already been proven to be effective -- condom use, behavior modification, protection of the blood supply, prevention of mother-to-child transmission, circumcision, pre-exposure prophylaxis in gay men, and topical microbicides.
We have a vaccine that certainly is not ready for prime time but at least the concept that we can have a vaccine has now been proven. That will be years away but just within the last few weeks we have had a real game changer in that it's been shown beyond a doubt what we already knew and strongly suspected from observational studies. We know now from a very good randomized controlled study among heterosexual couples that are discordant (one infected and one not) that if you treat somebody earlier rather than later, the early treatment has a major effect in diminishing the likelihood that the infected party will transmit the virus to their uninfected heterosexual partner.
Put all of those things together right now. We have the means in prevention where not only do we have prevention modalities but treatment itself actually can become a form of prevention. There was that tension for a while -- treatment or prevention? Now we can integrate treatment into the prevention modalities.
The problem the world is facing is almost less of a scientific gap than an implementation gap because the resources are very constrained for a number of reasons. The implementation is going to be very, very difficult. Right now, particularly with the recently reported data, a number of bodies -- UNAIDS [Joint United Nations Programme on HIV/AIDS], WHO [World Health Organization], different governments -- are relooking at this now and saying, "Should there be any change in recommendations and guidelines and resources?" We're at a very dynamic part of the epidemic at this 30th anniversary. We do have the capability of making a major impact.
Dr. Adashi: This might be a good point to reflect on the wisdom of investing in the epidemic upfront, in prevention, thereby saving later on by way of less disease burden vs remaining focused on treatment and really losing that opportunity upfront.
Dr. Fauci: I know your question is an extraordinarily appropriate question but what we're seeing now is that we should not be pitting treatment against prevention. We should be implementing prevention modalities but now we know that treatment actually is prevention, so we need to tear down these barriers of treatment or prevention and realize that we've got to implement all of the known prevention modalities. We can now insert treatment, so for every person you put on treatment it is no longer treatment or prevention, it is treatment as part of prevention.
Dr. Adashi: Yes.
Dr. Fauci: What we really do need and people are beginning to realize is that prevention almost never will be a unidimensional phenomenon. It will be a combination of prevention where there is not one thing that's going to be the show-stopper for HIV/AIDS. It's going to be a number of things that work synergistically together. That's what I see s the future for where we're going with HIV now.
Dr. Adashi: Let's go back now to the United States and focus more internally, as we have discussed worldwide issues thus far. How do you see the disease in the United States? Are we gaining? Where are the gaps? What else would you like to see happen? Do we have a plan?
Dr. Fauci: Yes. Well, the national strategy that President Obama has spearheaded through the Office of National AIDS Policy is a very good start toward the plan of where we're going. We have done very well up to now. We can do better. I see the challenges and the gaps pretty clearly in my mind. In the 80s, if we look at San Francisco and New York, the number of new infections in the United States was 120,000-150,000 new infections in any given year. It has gone down dramatically to 56,000. That's the good news. The bad news is that it has stayed at 56,000 for the last 10 plus years.
We've got to get below that and one of the reasons that I believe we're not is that we've got to be more aggressive in seeking out, voluntarily getting people tested, linking them to care, and getting them under treatment, and there are some good reasons for that. There are about 1.1 million people infected in this country. At least 20% of them do not know that they are HIV infected. The majority of new infections that are transmitted are transmitted from someone who doesn't know that they are infected.
We have a program, in collaboration with the CDC [Centers for Disease Control and Prevention] and with HRSA [Health Resources and Services Administration], where we're going out into the community in some sentinel pilot cities and seeing how far we can push the envelope about seeking out, identifying, voluntarily testing, and getting people linked to care. This gets back to what we were saying just a moment ago -- then all of a sudden not only are you helping the person who is infected but you are preventing them from infecting other individuals. So if we can implement that program what I would like to see, finally after 10 years of watching this flat line, is to see that 56,000 new annual infections go way down because once it does, then the dynamics of infectious diseases are such that it will be a self-propagating decrease because the fewer people that are infected the fewer will infect other people. So you've got to interrupt the dynamics of the epidemic in this country and globally.
Dr. Adashi: It may be too much to hope for today, but as you reflect about the prospect of cure someday, somehow, what comes to mind?
Dr. Fauci: Well, it is not going to be easy, but I believe it's feasible. At the NIH we are putting out a considerable amount of money [on this initiative]. I've been talking about the potential for a cure for several years now. I think the answer is going to be multiple approaches. We think of a cure either as a term I coined a few years ago -- "a functional cure" or as a "true microbiological eradication cure."
We know that we can treat people with combinations of drugs and get their virus load to below detectable level and they will lead very healthy lives. The issue is they need to be on therapy indefinitely, so we and others have studied very carefully a small recalcitrant reservoir of HIV. This reservoir doesn't bother virtually all patients when on therapy, but as soon as you stop therapy the virus begins to replicate again, with few exceptions such as people who are "elite controllers" who you didn't realize were elite controllers. So there are a couple of approaches. I believe that the earlier you start people on therapy the smaller the viral reservoir will be, so the less of a challenge you would have. We're working on new drugs now that might be able to get rid of that remaining reservoir.
There are things that are in early development like certain types of gene therapy experiments and protocols, with the goal to completely get rid of the virus. The other approach is to treat someone early enough so you suppress the virus but do it at a point where the person's immune system has not been so devastated that they would not be able to contain the virus when you withdrew the drug. That's where a new possibility for a therapeutic vaccine would come in, where you get somebody with undetectable viral load on treatment but instead of getting them late when they've depleted their T-cell repertoire, get them early so they still have a good immune potential left and boost that. That could be a functional cure.
The bottom-line, short answer is I believe it's feasible. I don't think cure is possible in everyone but I think in a certain percentage of people who are HIV infected we may be able to do that within a reasonable period of time.
Dr. Adashi: On the presumption that we are not likely to treat our way out of the epidemic and that prevention is rarely perfect, a vaccine always seems to be a feature in the overall plan.
Dr. Fauci: Right.
Dr. Adashi: We have had some good news in the last year or two. Most recently the simian virus was being experimented with and the results appear to have been promising. Could you summarize where we stand on the vaccine front?
Dr. Fauci: Let's take a look at what we see in humans and what we see in animal models. At the end of the day it is the human model that counts.
Dr. Adashi: Yes.
Dr. Fauci: The good news is that, as you mentioned, about 1.5 to 2 years ago we had a human trial in Thailand called RV144, which gave a modest at best 31% protection in people who were vaccinated vs those who were not vaccinated. That was a proof of concept. Unlike other infections, where it is usually clear that the body is capable of inducing an immune response that would clear the virus, eradicate it, and leave you with long-term immunity against reinfection, we don't have that with HIV. Amazingly, the body does not handle this well at all and there are no instances of anybody who has actually spontaneously completely cleared the virus.
Only until 1.5-2 years ago we didn't even have a proof of concept of whether this is possible. Now we believe it's possible but what we've got to do now is figure out how to precisely identify what correlates of immunity there are and whether immunity can be induced in a human. The human experiments are going in the direction of trying to figure out what the correlates of immunity are.
We have had some primate studies recently that have had some very impressive results, not necessarily in preventing initial infection but in developing an immune response that keeps the virus completely suppressed for a considerably period of time, and when you look for the virus you can't even find it. This means that maybe they got an initial infection but that infection was aborted, so there are a lot of exciting animal data, but there are also some very important things that are going on in human trials.
When are we going to get a vaccine? No one can make that prediction, but for the first time since the beginning, when I think about vaccines I think that there really is real light at the end of the tunnel. I don't know exactly when that's going to happen but a lot of things are happening now -- the identification of broadly reacting neutralizing antibodies, the ability to use very precise clonal techniques to pull out the B cells that are making these antibodies, and the identification of neutralizing epitopes on the envelope of HIV. The trick now is, "How do you get that epitope on the envelope and put it in the form that's immunogenic, which induces a response that protects?" But at least we have a road map of where we want to go, whereas years ago it was all empiric -- try this; it doesn't work, try that; it doesn't work. We are beyond that now. We really have a pretty good idea about what we need to do. It's going to take some time but we're going to do it.
Dr. Adashi: That is good news. We would probably be remiss if we didn't mention the role of advocates and activists in the last 30 years, and you happen to be in a unique position to comment on that through your interactions with Larry Kramer and with many celebrities along the way. Can you try to do justice to the role of advocates and activists in getting us where we are today?
Dr. Fauci: The very short version is that advocates have had a huge impact, a positive impact. Here is a little bit more detail on how they did it. I look at it in 2 phases. First of all, HIV/AIDS is a completely unique situation from a public, domestic, and global health standpoint. We in the scientific community, those in the regulatory community, and those in the public health community looked upon it as, "We'll approach it in the usual way we approach it. Everything has got to be pristine -- pristine clinical trials, going through 4000 hoops before you get a drug approved, designing a trial with all of these exclusion criteria."
The activists didn't buy that. They were saying, "This is different. We're all young. We're seeing our friends die and we don't have any treatment. It isn't as if there are 5 treatments and you want to do a trial to make a sixth one that's better. We have nothing. We've got to be able to be flexible on the clinical trial approach. We've got to loosen up the regulatory approach and do more. By the time a drug gets approved we'll all be dead," that kind of a thing.
So that's what they were saying. Then the issue was they needed to get the attention of the authorities and so they would do very dramatic, theatrical things -- invade the stock exchange, invade St. Patrick's Cathedral, invade the NIH and the FDA, with smoke bombs in theaters. Many scientists, when they see those things, they flinch and are quite conservative and they don't want these outside influences. The thing that I did that was very lucky and one of the things that I guess I'm most proud of is that right from the beginning, rather than get put aback by people who are being theatrical, you just forget about what they are doing and listen to what they're saying and read what they're writing, and they were making perfect sense. So the turnaround came for me when activists were essentially storming the NIH campus.
Because I was out there doing what I felt we needed to do, my face and my name were associated with the federal government, so I was the face of the federal government. So they figured why don't you just go and attack. You know, "Fauci, you're killing us." You're burning in effigy and all of those sorts of things. So rather than push them away, when they invaded the NIH campus, I told the police not to arrest them but to actually bring 5 or 6 of their leaders to my conference room and we'll sit down and talk about how we can start a partnership where we can get them involved and listen to them.
We didn't agree with everything they said because although they were mostly right they were incorrect on certain things, and that began a process to the point where, now that they had our attention, they were extremely valuable in giving us input in how to design the trials and determining the needs in the community to the point where, if you look on any of our advisory committees, any of our councils, there are always activists included. So it started off as an adversarial role, but they made a major contribution. I would think that among the top few things that were positive factors and positive issues in HIV/AIDS, embracing the activist community has to be right up there.
Dr. Adashi: They have shown us things we did not see.
Dr. Fauci: Absolutely.
Dr. Adashi: On a personal note, if I may, of all your multiple accomplishments in this arena and perhaps others, what are you most proud of? What do you feel stands out as a game changer during your professional lifetime?
Dr. Fauci: Well, there are a couple, and one that stands out more than others. I think the decision I made very early on when I was in the midst of a very successful career that had nothing to do with AIDS [was] to realize that I was going to change the direction of my research, much to the chagrin of my advisors, friends, and mentors, and start studying this disease. When I became the Director of NIAID in 1984, just a few years into the pandemic, I pushed as hard as I could to get more resources. I had the privilege of dealing closely with every President since Reagan through George H.W. Bush, Clinton, George W. Bush, and now President Obama with his global health initiative and PEPFAR [US President's Emergency Plan for AIDS Relief]. My scientific accomplishments are part of a big team.
A lot of people made scientific accomplishments but my working with the activists I think was a game changer in getting them involved. The thing that was really the game changer was I was in the fortunate position to have developed a close relationship with President George W. Bush, only because I knew him during his father's presidency, George H. W. Bush, but George W. Bush was keenly interested in seeing what we could do in the developing world and he sent me together with US Secretary of Health and Human Services Tommy Thompson down to Africa to figure out if we could come back with some facts. It was a fact-finding mission. When I came back we spoke to him about the opportunities and he said, "I want you to put together a program that would actually transform a game change or something where the United States of America will really have an impact on people in the developing world in Sub-Saharan Africa and the Caribbean."
I spent about 7 or 8 months of my life working 2 jobs. One job was running the NIH and the other one was putting together in a mathematical model sort of way -- what countries, how much prevention, how much whatever. I employed a person who was with me in my lab who then became my assistant, Mark Dybul, who ultimately became the second ambassador for PEPFAR.
I worked on that, going back and forth to the White House a lot, until finally we presented to the President and he said, "We're gonna do it," and that's how PEPFAR was born. He announced that at the State of the Union Address on January 28, 2003. We still have PEPFAR now and it's part of the global health program under President Obama. For me personally, to have had the opportunity and the privilege to work with the administration at that point to put together what is now clearly the most successful program in global health with the greatest impact that we have ever had --I am so pleased that I had the opportunity to have done that.
Dr. Adashi: It may be worth noting that that particular initiative converted the United States really to the largest donor on earth in global health in general --
Dr. Fauci: [interposing] Right. Exactly.
Dr. Adashi: -- in HIV/AIDS in particular, and we remain in that category. Thank you very much for the wonderful conversation. On that note, sincere thanks to Dr. Fauci and to you, our viewers, for joining Medscape One-on-One. Until next time, I am Eli Adashi.