HIV Frontlines: An Interview With Anthony Fauci, M.D.
June 12, 2008
Welcome to HIV Frontlines. Today I'll be speaking with physician and scientist Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, which conducts and supports research to understand, treat and ultimately prevent infectious, immunologic and allergic diseases.
As director, Dr. Fauci has overseen the development of national and international programs to fight HIV and other infectious diseases. From the very beginning of the pandemic in the early 1980s, Dr. Fauci has focused on HIV. His research has helped us better understand how HIV works and develop new strategies to treat it. Dr. Fauci was one of the architects of the U.S. President's Emergency Plan for AIDS Relief, known as PEPFAR. He is a widely published author and has won many awards for his scientific accomplishments. In June 2008, Dr. Fauci was given the country's highest civilian award, the Presidential Medal of Freedom, for his outstanding efforts to help people live longer and healthier lives with HIV. It's an honor to have Dr. Fauci with us here today.
Thank you, Dr. Fauci, for taking the time to talk with us. I wanted to talk to you after I read your essay in the May 2008 issue of Nature magazine. It's always interesting to hear reflections on 25 years of HIV. Can you describe your encounter with HIV in 1981? Where were you working, and what were people saying about these very first few HIV cases?
Anthony Fauci, M.D.
I can certainly remember it clear as a bell, because it turned out to be one of the real transforming times in my professional career, if not my own life. I was sitting at my office at the National Institutes of Health [NIH] in Bethesda, Maryland. I was an infectious disease physician and a basic science immunologist working on the interface between infections and the immune system.
I had been doing that for about 10 years -- nine years following my infectious disease immunology fellowship. I remember reading at my desk at the NIH hospital labs that there was a report of five gay men from Los Angeles who had pneumocystis pneumonia [PCP]. It was in June of 1981. I remember thinking that this was an odd curiosity. I couldn't figure out why a cluster of five gay men should have what looked like an immunodeficient state for no reason. There was speculation that maybe they had consumed a toxic drug that suppressed their immune system, but no anchor to any reality of what could be causing this.
About a month later, in July of 1981, another report from the CDC [U.S. Centers for Disease Control and Prevention]'s Morbidity and Mortality Report landed on my desk about over 20 people -- now not only from L.A. but from San Francisco and New York and, again, all gay men -- this time not only with PCP, but with Kaposi's sarcoma in some of the individuals.
I remember, at that point -- one of the first times in my still-young medical career -- that I actually got goose pimples thinking about what this might mean, because it sure looked like a new disease to me. It certainly smelled like it was an infectious disease, but none of us at that time had any idea what it was. There was a lot of speculation and a lot of guessing. Was this some sort of mutated form of cytomegalovirus or a similar virus that was commonly spread among gay men? Or was this, God forbid, a new microbe? That wasn't necessarily on the top of anybody's list; there was just a lot of puzzlement as to what was going on.
Then, over the next several weeks to months, the mystery began to unfold even more. It was not only gay men but also injection drug users who were starting to get this strange syndrome, which had inappropriately been called GRID, or Gay-Related Immunodeficiency Disease. After a few more months, there were more reports of women who were either injection drug users or possibly sexual partners of people who were infected, and then the first cases of babies born of infected mothers came months after that.
Over a period that began in the summer of 1981 -- a period of about a year -- there was a gradual unfolding of this extraordinary mystery about which we were all in the dark. It was highly suggested that this was a sexually transmitted disease and that it was an infectious disease.
It wasn't until the spring of 1983, in the paper by [Luc] Montagnier1 and his colleagues in Science, that there was the first suggestion that we were dealing with a new virus, in this case a retrovirus. It wasn't until the following year, 1984, when [Robert] Gallo2 and his colleagues showed the direct causative connection between this retrovirus and people who had this unusual syndrome.
It was a very eerie, depressing, anxiety-provoking period from the summer of 1981 through the spring of 1983. We were dealing with a disease that was growing in its numbers and its intensity, which appeared to be almost universally fatal. By the time patients got to a physician like me -- I was taking care of these people here in our hospital at NIH -- often they had very fulminant courses.
We didn't know at the time, but it was likely that they had been infected for several years before they even came to our attention. But once they got very sick, there was very little that we could do for them. I refer to those early years, when I talk about this, as the very darkest years of my professional career.
They were dark because all of the people you were seeing with this kind of syndrome died?
Yes. They died. They either died directly under my care or they went back home and you didn't hear from them again. The ones that we were seeing were all dreadfully ill. We didn't get the opportunity to study people in the very early phases of disease.
For example: Now that we have a very sensitive diagnostic test, if someone gets infected, they may not get sick without any therapy for a relatively long period of time. They're walking around looking and feeling very well. Back then those patients didn't come to us in the hospital because they had no idea they were infected. It was only after the screening test became available that we started to see people much earlier on in the course of their disease. That's when we had the opportunity, over a period of time, to take care of them before they became dreadfully ill.
There was another era, or period. I mentioned that the first few years of not knowing what we were dealing with were the darkest of the years. Once the virus was discovered in 1983 and 1984, we went through another few years, until 1987, when there were no drugs at all. It was only in 1987, when the first drug, AZT [Retrovir, zidovudine], was approved that we gained some hope that we could actually do something for these people.
There was some optimism early on when AZT was used, but it became very clear after a while that the virus soon became resistant to a single drug. It was only, literally, another nine or so years later -- in 1996, when the combinations of drugs [were developed], including the protease inhibitors -- that we had a real transformation in how we were able to take care of HIV-infected individuals.
From 1987 to 1996, we did some good. People benefited somewhat from the drugs, but the benefit was transient. You didn't suppress the virus completely to below detectable levels the way we are able to do right now with combinations of drugs. That period from 1986, when AZT clinical trials began, to 1996 was a period that was certainly better than the time before there were any drugs, but we still had the feeling we were losing the battle against HIV because we didn't have the best possible combination of drugs. It was only, as I mentioned, when we got to 1996 and beyond that we witnessed dramatic improvements in patients.
How did you diagnose the early cases before there was a test?
Purely clinically. It was diagnosed because they came in with what would soon turn out to be a characteristic syndrome. When we were dealing with the first handful of cases, we had no idea what was going on except some common threads that linked the patients. They were gay men. They had these diseases like PCP and Kaposi's sarcoma, which almost exclusively are seen in immunodeficient people. Some of them had some epidemiological connection between them -- sexual contact with each other or what have you.
It was merely a pure clinical diagnosis, made on a set of criteria that evolved over a period of months. These became the criteria for the diagnosis of this disease, even without laboratory confirmation. Only after the virus was discovered, and the diagnostic test was developed, were we able to confirm the diagnosis of AIDS in people who clinically had a syndrome that looked very much like AIDS. It was nailed down when the confirmatory laboratory tests were done.
This was in the early days before the Internet, before e-mail, and it was happening on both coasts. It was in L.A. and San Francisco, and New York and Washington D.C., so how did the first researchers who were looking at this communicate with one another?
We communicated the way we communicated before the facilities that you mention, e-mail and the Internet. We communicated by phone, by writing, by discussing at meetings, by travelling to meet each other. I went to San Francisco several times, went up to New York several times -- more than several times -- continually travelling back and forth trying to figure out what was going on.
In those early days, you were all piecing together the puzzle and describing the syndrome: What did it look like? What were the symptoms?
That's exactly right. We were writing them up. There were people -- in the beginning, exclusively gay men -- who had a profound immunodeficiency manifested by defining diseases that you only see in immunodeficient people. Those characteristic diseases were PCP, Kaposi's sarcoma, cytomegalovirus, toxoplasmosis, atypical tuberculosis, candida, candida esophagitis, and a variety of other types of infections, including cryptococcosis and cryptococcal meningitis. These were all diseases that you almost never see in otherwise healthy people. They clustered among people with this rather bizarre syndrome.
Now they're the 16 AIDS-defining opportunistic infections, right?
Did you ever expect that you would be working in HIV all these years?
In the beginning, we were not sure what was going on. When we saw the virus that was discovered as the cause of AIDS, we thought that we would then be able to develop therapies, which we were successful in doing. It took many years before we got successful therapy, but what none of us were able to predict was the absolutely, breathtakingly depressing scope of this. It went from handfuls of patients in cities like New York City to becoming one of the most devastating pandemics in the history of civilization. I would never have predicted in the summer of 1981, when I saw my first cases, that this would be a disease that, 27 years later, would have infected over 65 million people and killed over 25 million people. I don't think anyone would have predicted that.
What has kept you in the field? Have all the medical developments been very exciting to watch? Some people have gotten discouraged.
Sure, some people have gotten discouraged. Some people have gotten burned out. I was driven by the enormity of the problem and by the fact that, as a researcher and as a clinician, I could make a contribution to it. As a science administrator I could marshal and argue for greater funding for both research and public health endeavors.
What's kept me through it over the years is that it's a very exciting field. It's also devastating, obviously, when so many people are getting sick and dying, now throughout the world.
The science is very exciting. We've made some very important advances in science, and we've been able to translate these advances particularly to drugs that have a major positive impact. We're trying very hard to help in preventive modalities. You can't just address this pandemic with treatment alone. You have to have prevention. One of the major components of prevention is the development of a vaccine, and that's one of the things that we're working on.
It's a field that continually changes, and continually is very challenging. It's the challenging nature, the enormity of the problem, and the possibility that we can do some good that has kept me involved in it so intensively over the last 27 years.
In your article, you say that unlike many other diseases that affect mostly the poor and the disenfranchised, HIV captured the attention of so many people, including world leaders, the medical community, activists and celebrities. These same people were not activated by the fact that malaria was killing millions of people in the developing world or that millions of women die in childbirth every year. Can you conjecture why there was such a dramatic scientific and public health response to HIV and why it interested all these people?
I'm certain why, and I've written about it in the article. What I think happened is that you have these diseases like malaria, which kills 1.3 million people a year, and tuberculosis, which kills 1.6 million people a year, almost exclusively in developing nations. Diarrheal diseases, respiratory diseases, neglected tropical diseases. Most of the developed world looked upon that as somebody else's problem, because you don't usually see those types of things in the developed world.
We had a very interesting circumstance with regard to HIV because it was first recognized in the developed world -- in fact, in the United States of America, in Los Angeles, San Francisco and New York. We became very aware of, frightened by, impressed with, and involved with HIV/AIDS right from the very beginning.
As it ultimately turned out, HIV is a disease of the developing world much more than it is a disease of the developed world. Ninety percent of all the infections are seen in low- and middle-income countries, and 67 percent of all the infections are in Southern Africa.
What happened was that we became acutely aware of the devastation of HIV not only in the United States, but also in developing nations. When we went to Africa to explore what was going on there with HIV, we came face-to-face with the enormity of the problem of malaria and tuberculosis.
In some paradoxical way, attention has now been put on malaria and tuberculosis and neglected tropical diseases merely because they are diseases that tend to travel with HIV, if I can use that metaphor. If you go to developing countries in sub-Saharan Africa, the three big killers are HIV, malaria and tuberculosis, together with neglected tropical diseases. All of a sudden, the developed world was fully cognizant of the fact that malaria is a great killer and tuberculosis is a great killer. Because of that, a lot more attention is now being paid to malaria, when several decades ago it was thought of as someone else's disease that no one really knew or cared a lot about.
One of the spin-offs of the devastation of HIV has been the positive effect of calling attention to other diseases that also deserve our resources and attention, such as malaria and tuberculosis.
You say that HIV/AIDS is predominantly a disease of the developing world, but isn't it true that places like Washington, D.C., Baltimore, New York and the Southeast U.S. have huge rates of infection in communities of color?
Absolutely. In fact, some sections of our society are just like the developing world. You mentioned Washington, D.C., which has the worst problem of any city or state in the country. It has nine times the incidence of HIV compared to most other cities. An astounding figure of 5 percent of the entire population of the District of Columbia is infected with HIV, and 2 percent have AIDS. It's very predominantly and very disproportionately impacting the African-American population. Washington, D.C. is 60 percent African American. Eighty to 90 percent of the new cases we have each year in D.C. are among African Americans.
In the United States as a whole -- and this is reflective of what we're seeing in cities similar to Washington, places like Baltimore, Newark, and other places with a high density of HIV infection -- of the new infections each year among men, 49 percent are among African-American men. Of new infections among women, 65 percent are among African-American women. Yet African Americans comprise only about 12 to 13 percent of the United States population. There's a great disparity and a disproportionate burden that's borne by African Americans.
I know this is not really your focus, but do you have any ideas about why HIV has settled into this population so powerfully?
There are a number of reasons. There's a confluence of events: the issue in the inner city of injection drug use; the spillover of injection drug use by heterosexual contact; sexual partners -- young women -- of male injection drug users get infected; women themselves who are addicted to crack cocaine sell sex for crack. They can get infected and pass it on to their sexual partners.
It becomes a confounding issue of everything from injection drug use to stigmatization associated with homosexuality among gay men who are African American.
Do you think that enough is being done to address the epidemic in this population?
No, I don't think so! We all know that we need to do more in everything. We need the community leaders to step up to the plate. The African-American clergy need to do more. I think the city, state and federal governments need to do more. We all need to do more. This is a very serious problem in that population.
I wanted to go back to talking about HIV research. I thought it was interesting that research moved so quickly after HIV was discovered. Why do you think research in HIV has made such strides in developing such a large number of effective drugs and turning an almost invariably fatal disease into a manageable one, while researchers studying other diseases -- other viruses -- have still not made much progress?
I think it's pretty clear that the amount of resources that have been devoted to HIV is extraordinary. The NIH spends about 11 percent of its entire budget on HIV research: $2.9 billion per year. Also, pharmaceutical companies are very heavily invested in working with the government and academia in developing drugs, because these are drugs that people have to take for the rest of their lives. The possibility of a huge profit margin is great. These are blockbuster drugs, when they work, because there are millions and millions of people who will be taking these drugs for the rest of their lives. Not only is there investment in the government research enterprise, but there's also a great incentive for pharmaceutical companies to get involved in developing drugs.
That's not the case with diseases like malaria or tuberculosis or other types of infections, because the incentive and the market for developing interventions for those is not nearly as great as is the case with HIV.
The pace of HIV understanding and drug development seems so fast, and the assumptions are continually upturned. As a researcher, what has been your experience standing on the frontlines of this?
It's exactly what you said: There's an extraordinary rapidity of understanding, of discoveries, of advances. There are a lot of researchers who are working on HIV. There's an enormous amount of money that's put into that. If you compare, we spend $120 million a year in research on malaria at the NIH. We spend $2.9 billion on HIV. That in and of itself can explain the difference in advances in biomedical research related to those two different diseases.
Do you think that these advances in research help because many of the HIV researchers were gay, and so it made the disease all that more personal?
No, I don't think so. Certainly there are gay researchers in every discipline. I think that, in the big picture of things, gay researchers have made major contributions, as have straight researchers. I don't think because there are many more gay researchers, as you said, in HIV, that that has had a major impact on the ultimate outcome.
What impact do you think the early activism by ACT UP and other groups had?
I think it had a positive impact. They really demanded to have a say in things like the design of the clinical trials, as opposed to the trials being very restrictive when there were really no drugs available for people. The exclusionary nature of clinical trials was unacceptable to them, and they were correct in that.
The rapidity with which drugs would be approved by the FDA [U.S. Food and Drug Administration] when there was a fatal disease for which there were no drugs available -- they demonstrated against that. A lot of the points that the activists made in the early years, and even today, were very, very valid points. I think they opened the eyes of researchers, public health officials and government officials to pay more attention to the kinds of needs that people with HIV infection, or at risk for HIV infection, had.
All in all, I think the activist movement was a very positive thing in HIV.
Did you feel that way in the beginning, when you were being shouted at?
Yes, I did! That's the reason why we ultimately came to an agreement. I realized, although they were shouting at me and yelling at me, it really wasn't something personal. It was a great pain and a fear and a concern that they were feeling, and I was very empathetic towards that. That's the reason why we developed very good relationships, ultimately, with them.
But you're right. In the beginning, they were very confrontational because they needed to get our attention. Indeed, they did get our attention. They certainly got my attention.
You say in your article that we must do better at delivering HIV prevention and that less than 20 percent of those at risk for HIV infection are currently receiving such help. Which people at risk were you referring to?
If you go through the list of men who have sex with men, the idea of behavior modification -- counseling about how they can avoid their risks -- less that 20 percent of those people have access to that. The distribution of condoms by people who would benefit from the use of condoms: Less than 12 percent of them get it. Injection drug users who can benefit from clean needles and syringes: Again, less than 20 percent of the people who could benefit from them are actually getting them.
There are a lot of preventive modalities that are available and proven to be effective. In general, when you add them all up, less than 20 percent of the people who would benefit from them actually have access to them. We've got to do better in making these modalities of prevention accessible to the people who would benefit from them.
You mentioned how critical it is to provide clean needles and syringes. Why, 25 years into this pandemic, has the scientific community been unable to convince politicians to allow for syringe exchange in their states?
There are several states that actually do fund needle-exchange programs. The federal government does not. I made a recommendation a long time ago that we should be funding needle exchange programs. The federal government has not accepted that recommendation, but several of the states have.
You mentioned that circumcision is the newest way to prevent HIV, at least in the developing world. Why do you think circumcision doesn't seem to be a factor in the developed world?
It's the rate of infection that one sees. For example, the rate of infection in countries in which there are a number of other sexually transmitted diseases that confound the probability of transmitting it and make it worse if you're uncircumcised. Whereas in the developed world, in which, for example, in the United States, the majority of people are in fact circumcised, there's less sexually transmitted disease in addition to HIV. The impact is less when you have a much lower rate of transmission and a much lower incidence and prevalence. It's when you get into those countries, such as the countries where we do the [circumcision] trials in sub-Saharan Africa, where the incidence and prevalence is very high, that circumcision makes a difference.
Why do you think it has been so challenging to find an HIV vaccine?
It's pretty clear that the body does not make an adequate immune response against HIV when it's naturally exposed to the virus. In most of the vaccines that we successfully make, we model our vaccine development against natural infection. Even if you take devastating diseases like malaria, measles, smallpox, polio, those viral diseases are diseases that -- even though people die and suffer from them -- ultimately, the body mounts an immune response that successfully eradicates the virus from the body. Researchers go to a person who's been infected and look at the nature of the immune response that's been elicited by natural infection. A vaccine is then developed that mimics the development of that response. That's how you get a successful vaccine.
Unfortunately, HIV is very different. HIV does not naturally elicit a good protective immune response against this particular virus. We don't even know if the body is capable of eliciting a protective response. So when we develop a vaccine, we have to do better than natural infection. Thus far, we've been unsuccessful in doing that.
It really is a question not necessarily of not picking the right vaccine, but of whether or not the vaccine is even going to ever be able to induce a response that would be protective. That's a very formidable scientific challenge.
Are we looking at another 10 years, 20 years --
It's impossible to predict. It would be folly for me to give you a time frame because I don't have any idea how long it's going to take.
You say in your article that we're in the infancy of discovering something.
It's a long way away. You end your piece in Nature magainze by saying that history will not judge us kindly if we don't deliver HIV interventions for the people it most affects. Were you talking about people in the developing world, or people most affected in the U.S., like the incarcerated, African-American men and women --
I'm talking about all of those people who need access who don't have access, both in the developed world and developing world, although the problem is much more profound in the developing world. Because, like I mentioned, even though we're doing much better in getting treatments to people who need them, only about 28 to 30 percent of the people who actually need HIV drugs are getting them.
I referred to [what we need] when I made my address before the United Nations General Assembly a couple of days ago. I referred to it as the implementation gap: the gap between the fruits of HIV research in the form of prevention and therapy, and getting those fruits delivered to the people who really need them. In other words, we're not implementing the programs that allow access to the people who need these interventions.
Why aren't we implementing them?
It's very, very difficult when you're dealing with poor countries and you're dealing with governments that are not particularly organized to do this. You have to assist and you have to get leadership from them. Sometimes you don't get the leadership that is needed and it costs a lot of money. That's the reason.
What has been the most important thing you have learned being at the frontlines of this pandemic?
I think the most important thing is that we have a very formidable problem. We have to keep pushing and we cannot give up. We've done an awful lot. I use the terminology "much accomplished, much to do." We've accomplished breathtaking advances in science, but we still have a moral obligation to do much, much more. That's the thing that's impressed me the most.
Is the NIH budget for HIV going up or going down?
It's been flat over the last few years, as the entire NIH budget has. Over the years, it's rapidly accelerated. But for the last five years, the whole NIH budget has been relatively flat.
Do you hope that the coming administration may look at it again and --
I hope so.
Is that something you'll be working on?
Thank you very much, Dr. Fauci, for taking the time to talk with me.
You're quite welcome. It was a pleasure.
This article was provided by TheBody.
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