New Momentum for AIDS Research:
The amfAR Interview with Anthony Fauci, M.D.

October 2011 - Since 1984 Anthony Fauci, M.D., has served as director of the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health, where he oversees an extensive research portfolio aimed at preventing, diagnosing, and treating infectious diseases including HIV/AIDS.  Dr. Fauci is also a key advisor to the White House and U.S. Department of Health and Human Services on global AIDS issues and was awarded the Presidential Medal of Freedom in 2008. 

amfAR: There have been major developments in HIV prevention research in recent months. What do you think it is going to take to realize the potential of this research and what are the major challenges that stand in our way?

Dr. Fauci:  I think we have to look at prevention as an issue that has evolved over several years.  From the first day, we suspected we were dealing with a sexually transmitted disease, even long before we identified the virus.  We knew that safe sex practices and behavior modification were at the core of prevention, but getting people to change their behavior is very difficult to do.

Over the last several years, we have begun to look at prevention not as a one-dimensional issue but rather as a combination of modalities.  We had the 076 study of mother-to-child transmission prevention followed by the short version of that study with single dose nevirapine.  Over the last few years, we have discovered that male circumcision is extraordinarily effective in preventing acquisition of HIV infection among heterosexual men.  And then we had the topical microbicide breakthrough.  We now have the PrEP [pre-exposure prophylaxis] study for gay men and the PrEP study for heterosexual couples.  And we have the game-changing HPTN 052 study, which has really taken down the boundaries between prevention and treatment by establishing that treatment is prevention.  We now have within our armamentarium the tools that, if implemented and adhered to properly, can turn around the dynamics of the global HIV pandemic.  That is true even in the absence of a vaccine.

What we really need to do right now is implement these tools.  Implementation in an arena of constrained resources, particularly in the developing world, is going to provide a serious challenge.  But it is a challenge that we need to rise to and meet. 

amfAR: How do you assess the prospects for vaccine research?

Dr. Fauci:  I can tell you that a few years ago, I very conservatively said I was not sure that we would actually be able to develop an HIV vaccine because there was no proof of concept that any product could actually have an impact on acquisition.  Then we had the RV 144 trial, which─even though the results were modest at best with only a 31 percent efficacy─I feel represented a proof of concept.  So while it is impossible for me to predict when we are going to get a vaccine, I think we can say, not with absolute certainty but with some degree of confidence, that we will ultimately develop a vaccine to prevent acquisition of HIV infection.  I certainly am much more optimistic about it now in 2011 than I was five years ago.

amfAR: Can you tell us in broad strokes about the NIH/NIAID strategy on cure research?

Dr. Fauci:  To me the definition of a cure is to have a person be disease free in the absence of therapy, and this can happen in two ways.  The first way is complete eradication of the virus in the body.  We clearly do not yet have in our armamentarium of drugs the agents to completely rid the HIV reservoir of any trace of the virus.  We have to develop innovative approaches for that.  I think pure eradication will be a very difficult task.

The other type of a cure is what I have referred to over the years as a functional cure.  You do not necessarily eradicate every vestige of the virus from the body, but you try to develop a situation where you do not have any good targets for the virus to replicate in.  Alternatively and probably with less difficulty, you can treat people early on in the course of their disease so that their HIV reservoir is very small, and then you enhance  the body’s own immune system, such as with therapeutic vaccination,  to keep whatever virus remains in the body in check even after you discontinue antiretroviral therapy. 

And so cure means being disease-free without noticeable virus replication in the absence of therapy.  We are pursuing with our research agenda both eradication and functional cure.  We have made a considerable investment all along in research pertaining to the kinetics of the HIV reservoir.  And we have now committed $14 million a year over five years to [cure-focused research at] the new Martin Delaney Collaboratory because we really want to try to galvanize and catalyze the field.

amfAR: Not long ago cure was kind of a dirty word─a fantasy─in AIDS research.  Was there a moment in time when you woke up and thought, maybe this is possible after all?

Dr. Fauci:   It was not an “Aha!” moment where all of a sudden something happened.  It was just my own experience as a physician, where I and many others were seeing so many patients who have been followed for years and whose virus is extraordinarily well contained.  The studies of the reservoir showed that the earlier you treat, the smaller the reservoir.  Patients were doing so well on antiretroviral drugs, and so the next logical question was could we ultimately take them off drugs without relapses that we consistently saw when we tried to discontinue drugs in the past.  It was just a gradually growing confidence in the capability of drugs to suppress this virus in a way that allows people to live a really, really long time. 

Also─looking from a broad 30,000-foot policy standpoint─with much greater numbers of people living with HIV today than ever before, it would be wonderful, given the constraints on resources, if we could get some of these people off therapy.  Perhaps we could accomplish this with a different class of drugs or with a different approach.

amfAR: How do you see advances in cure-focused research reaching people in resource-limited settings?

Dr. Fauci: That is going to be a challenge, and it depends on the type of cure that we develop.  We have a moral commitment to treat as many people as we can.  But it is not incompatible to attempt to develop a cure at the same time as you are trying to treat as many people as you can in the developing world.  I do not think that cure research is diverting away from the implementation of treatment programs.  You do not want to pit basic research to try and find a cure against the efforts to try and get as many people on treatment as possible.  We are pursuing both approaches.

amfAR: There is a lot of debate right now about PrEP and its implementation.  When many people in developing countries still don’t have access to antiretroviral drugs for treatment, how do you reconcile using ARVs for prevention with PrEP?

Dr. Fauci: That is a reasonable question, which is why I hold the opinion that PrEP is not for everyone.  It is not one size fits all.  There are certain groups of individuals whom you might want to target with PrEP.  PrEP is not for every country or every situation within a country.  It should be used selectively in targeted populations where you can get the most benefit.

amfAR: What is your biggest concern about the possible impact of budget cuts for HIV research at NIH?

Dr. Fauci: We have been fortunate, even though there have been great budgetary constraints, that we have not been hit hard by actual cuts.  I am hopeful that this will continue.  I believe there will be budget constraints for the next few years, and I will continue to try to make the case as forcibly as I possibly can that, in the arena of HIV, money invested in research now will ultimately save us a considerable amount of money in the future. 

And the history of AIDS science has proven me correct over the years.  An enormous amount of money is already being saved now as a result of the transforming advances that we have made not only in treatment but also in some of the prevention modalities we spoke about in the beginning of the interview.  I think that makes a very strong case for the investment in HIV science.  Not only is it important in saving lives and preventing infection, but it is also going to save a lot of money in the future.

amfAR: And speaking of the future, a final question─ given everything you know about research and the epidemic , how are we going to bring this global HIV epidemic to an end?

Dr. Fauci: I do not have a crystal ball, but I think we have some road maps.  Number one: We have extraordinarily effective therapy.  Number two: We now have scientifically proven, highly effective modalities for prevention.  Number three: We now know that treatment itself can serve as a major form of prevention.

I think that if we get global, political, local, government, and private sector commitment, we can actually turn around and end this AIDS epidemic.  I think we can do it, but we need that commitment, which is going to save not only a lot of lives but also a lot of money.  The pandemic is not going to go away by itself.