Thursday, June 2, 2011

Anthony Fauci reflects on 30 years of AIDS

Anthony S. Fauci, MD, is arguably the U.S. government’s best-known scientist. While he has testified to Congress on more than 200 occasions and interacted with every U.S. president since Ronald Reagan on a variety of issues, he is known most for his work on HIV/AIDS. He was appointed Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH) in 1984, and oversees an extensive research portfolio of basic and applied research to prevent, diagnose, and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism.
Diagnosing HIV without using an HIV Test 

John Donnelly interviewed Dr. Fauci for Science Speaks’ series on the 30thanniversary since the discovery of a virus that would turn out to be HIV, and he talked about everything from how he first learned of the disease, to his surprise in President George W. Bush’s commitment, to the unmet needs today to fight the pandemic.

How were you first involved in the AIDS epidemic?I’ve been involved from the beginning, and I’m still here. Over a period of 10 years, from 1972 to 1981, I was a rather successful clinical immunologist-type person with a clinical interest in infectious disease. Through luck, among other things, I found myself on a project that was developing essential treatment, if not a cure, for some unusual diseases characterized by the inflammation of blood vessels… Then one day, and I don’t mean to be melodramatic, while sitting at my NIH office in the clinical center – June 5, 1981 – the Center for Disease Control and Prevention’s (CDC’s) Morbidity and Mortality Weekly Report landed on my desk and it reported five gay men, from Los Angeles, otherwise healthy, presenting with this strange pneumonia, Pneumocystis pneumonia, which we used to see on clinical patients with cancer. I was familiar with this and that it was seen only in persons with dramatically suppressed immune systems.
I remember putting the issue to the side of my desk, thinking, ‘Wow, what a bizarre curiosity.’ One month later, in July, a second Morbidity and Mortality issue came to my desk, and this time, an additional 26 men had it, again all gay, all seemingly healthy, and not only in LA, but now also in San Francisco and New York City. I remember reading it very clearly. It was the first time in my medical career I actually got goose pimples. I no longer dismissed it as a curiosity. There was something very wrong here. This was really a new microbe of some sort, acting like a sexually transmitted disease.
In retrospect, it was a game-changer of my career. It completely changed the direction of my research away from a rather successful practice of bringing in patients and studying them to bringing in sick patients who had no idea why they were sick. I was treating people successfully for 10 years and went to a period over the next few years in which the median survival of my patients was measured in weeks, 28 weeks. I went from happy years of making people better to a period of close to a decade of the dark years in which most of my patients died.
After these dark years, what was most memorable?There was the discovery of AZT [or zidovudine, the first antiretroviral approved for the treatment of HIV] in 1987, then single and double combination of drugs the next couple of years, and then, in 1996, came highly active antiretroviral therapy. That was truly a transforming phase in the history of HIV. Now, we had patients, destined to going to hospice, who were all getting well. We went from 28 weeks median survival to now, in 2011, where the mathematical modeling of a 20-something-year-old person with recently diagnosed HIV who is put on antiretroviral therapy will live at least another 50 – that’s five zero – years. That is one of the most profound accomplishments in the relationship of biomedical research and drug development and clinical outcome.
The other historical issues for me personally were the interactions I had with various presidents and various members of Congress. I had the experience of all the differences on HIV/AIDS from Reagan to George H.W. Bush, who took a significant interest, to Clinton and George W. Bush and Obama. During the Reagan years, President Reagan didn’t speak hardly at all about HIV/AIDS, and so when people thought about the federal government and AIDS, they would think of me and Jim Curran (then the chief of the research branch of the Division of Sexually Transmitted Diseases at the CDC). So when the activists started to appropriately react to the rigidity of the clinical trials, for instance, they started storming the NIH and burning people like me in effigies, and Larry Kramer, now a close friend, was calling me a murderer.
The best thing I’ve done from a sociological and community standpoint was to embrace the activists. Instead of rejecting them, I listened to them. I remember looking out a window and people on the lawn of the NIH were throwing smoke bombs. The Montgomery County Police were ready to arrest them and I said, ‘Don’t. Bring them up to my office so I can talk with them.’ The interaction with the activists was a major chapter in the 30-year journey of this.
Another thing that was very important in the 30 years to me was when I was asked by George W. Bush to go to Africa to put together a proposal for a program to fight AIDS. He said he wanted a game-changer that would impact the developing world. He sent me to Africa in 2002 to look at the feasibility of a program for treatment, prevention and care. I spent seven or eight months in 2002 putting together mathematical models of how many countries can we do this in, what was feasible, what would it cost, what was the best approach. I employed someone to help me out, a fellow in my lab, Mark Dybul, who later went on to become the U.S. Global AIDS Ambassador. We presented the options multiple times to the president’s staff, and to the president himself, and he accepted the proposal for $15 billion over five years. That become what we now call the U.S. President’s Emergency Plan for AIDS Relief, or PEPFAR.
What surprised you most in your interactions with the presidents? Was it Bush’s decision?
It was surprising that it was with George W. Bush. A lot of people speak a good game about what they want to do. He said I want to do something transforming and he did it. He wasn’t particularly popular at the time. It was right before the Iraq War and he looked us in the eye and said, ‘We as a rich country have the obligation to do things for those who are less fortunate than we are.’ It surprised me he mandated something for $15 billion. People in the Office of Management and Budget laughed at us when we suggested $15 billion. They said, ‘For foreign aid? Are you nuts?’ But the president said, ‘Yes, I want to do it.’
How did you come up with the target numbers for treatment, care, and prevention, and for the price tag of PEPFAR?
We consulted with a lot of people. It wasn’t just me and Mark Dybul. It was Mark and I and a couple of modelers and we were relying heavily on the advice of African colleagues who were already doing it, people like Peter Mugyenyi of Uganda. He had a model that had a central core of treatment, with clinics, and it became less sophisticated care as you went out farther and farther from the center, but everything was linked together. We also picked countries in which we would get at least 50 percent of all the infected people in the world. We figured out that of those people, about one-third of them would require therapy right now given their stage of infection. So in the beginning, the budget was heavily weighted toward therapy early on – more than 50 percent was for treatment; just 20 percent was for prevention. But now as we get better prevention modalities, prevention is becoming a greater share of the pie.
In looking ahead, what are the unmet needs now?The challenges are really in the arena of prevention. For every person we put on treatment, two or three people get newly infected. But if we have a microbicide, a moderately effective vaccine, treatment as prevention, voluntary medical male circumcision, the possibility even of a cure for HIV, there’s a lot of things going on now that are both exciting and challenging.
I see unmet needs in two ways – unmet scientific needs and unmet implementation needs. One is as important as the other. The implementation need now has an impact on the scientific need. We’re starting to see that the earlier you are put on therapy, not only is it better for that person’s own health, but it possibly creates a decrease in transmission overall. We are starting to get very good cumulative data on discordant couples – where the infected partner is treated and not only is it good for them, but it prevents them from infecting the HIV-negative sexual partner. We have cohorts in cities, like Vancouver and San Francisco, where they are universally treating everybody and you see a correlation between treatment and the levels of infection in the community.
Of the scientific challenges, the Holy Grail is going to be a vaccine. I don’t think, and my colleagues agree, that there will be a singular prevention modality. If we are going to put an end to HIV/AIDS, the dynamic will be a combination of prevention modalities. It could be topical microbicides, pre-exposure prophylaxis, male circumcision, and even a vaccine that is a bit more effective than the 31 percent we got from the Thai trial.
The other one is trying to find a cure for HIV – the most daunting challenge of all. I have an idea we might be able to cure at least a fraction of people. It’s probably too much to ask that we will have a universal cure for HIV. But in some, we will likely be able to discontinue therapy with a certain fraction of new drugs, working by different mechanisms than the current drugs, by starting people early on therapy so the reservoir of the virus becomes much lower.
Obviously, increasing treatment, and using it as prevention, is going to cost a lot more money than is being talked about today.Yes. It depends when you want to spend the money. You can spend it now and put your arms around the epidemic and change the kinetics of it so you don’t have 1.8 million people dying every year and 2.8 million people infected every year. You need to seek, test and treat, and link all of them to care. If you don’t put in the money now, sooner or later you are going to have to pay at the end of the spectrum. And if you do that, at the end of the day, the amount of money spent is going to be much more. I am totally sensitive to the financial constraints we have, but I believe in the big picture of things, investing more money now is the way to go.

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