 |
|
|
 |
|
 Interview with
Dr. Anthony Fauci
Head of the National Institute of Allergy and Infectious Diseases at the N.I.H.
Page 1
Page 2
Page 3
Page 4
CBS CARES: Are there any HIV/AIDS vaccines in development now that, in your opinion, look promising?
DR. FAUCI: There are a number of candidate vaccines that are in development for HIV/AIDS. But the development of an HIV vaccine is going to be quite problematic, basically because of the fundamental nature of the virus and its ability to elude the immune system's capability of eliminating it or protecting the body against the virus.
There are a number of candidates that are at various stages of clinical trials. Some vaccines are in very early development. Some are in animal models. And there are some that we have already started to test in human safety studies. But I have to caution that the task of developing an HIV vaccine is going to be formidable. It is more formidable than most, if not all, of the vaccines that we've been challenged with developing over the years.
CBS CARES: You explained the virus' ability to evade the immune system. Can you please elaborate on how this and other complexities of the HIV virus make development of a vaccine so formidable?
DR. FAUCI: Well, a number of reasons. The nature of a protective immune response to HIV is still unclear. Because in a very, very unique manner, unlike virtually any other microbe with which we're familiar, the HIV virus has evolved in a way that the immune system finds it very difficult, if not impossible, to deal with the virus.
Let me give you an example. If you look at the history of infectious diseases, even some of the great killers of history: smallpox, polio, measles--the types of diseases that have actually fashioned civilization because of their impact--the body is usually able to ultimately handle those infections.
For example, only about 15 to 25 percent of people who get smallpox die. The other 75 to 85 percent do very well and their body completely eliminates the smallpox virus. The same holds true for polio. Only a very small percentage of people who get infected with polio are not able to handle it. But, for 90-plus percent of people, their own body ultimately protects them against the complications of these infections.
And then, once the body meets with the microbe, it develops an immunity, which protects it against subsequent challenge. That's just not the case with HIV. Of all of the tens of millions, actually a total of over 60 million people who have been infected with HIV worldwide, there are virtually no documented cases of people, once they've had established infection, who completely eliminate the virus from the body. So, for reasons that are still somewhat puzzling, the body is incapable of completely handling the HIV virus. And, since that's the case, it is very difficult to contrive and develop a way to present the virus in a manner, which would induce a protective immune response.
So it's a very difficult scientific issue that is clearly more challenging than the scientific issues with which we faced when we successfully developed other vaccines. In addition, the virus has an enormous capability of mutating and escaping the body's immune defenses.
CBS CARES: Despite the unique complexities of the HIV virus, do you believe that an effective HIV vaccine or cure is viable in our lifetime?
DR. FAUCI: Well, anything is possible. But there are many challenges associated with that goal. Let us take therapy first. We have excellent therapies that are capable of suppressing the virus to below detectable levels over an extended period of time, particularly in individuals who start therapy with a very potent anti-retroviral therapy that immediately turns off virus replication to avoid the emergence of resistance.
What we have not been able to do is to completely rid the body of virus. And that's what you, technically speaking, call a cure--when a virus is completely gone so that when you stop medicine, the virus does not rebound. That has been a goal that has eluded us up to this point. Likely because the virus has a way of inserting itself into the genome of cells that essentially protects it from getting eliminated by the anti-retroviral therapy.
So you have a constant reservoir of virus. Functionally, it might be considered equivalent to a cure if the virus remains suppressed while a patient receives therapy. But in the stricter sense, it is not because in most of the experiences with people taken off therapy, even those who have done very well, the virus ultimately rebounds. So I'm not sure whether we're going to be able to ultimately cure the virus. But we very likely may be able to control it for prolonged periods of time.
CBS CARES: Why are antibodies essentially unable to control the HIV virus? Is it that HIV compromises B cells and the quality of HIV antibodies is therefore defective? Or is it that the antibodies just don't work against this virus at all?
DR. FAUCI: Actually the virus does not predominantly infect B-cells. It predominantly infects CD4-positive T-cells. B-cells are indirectly negatively impacted by the virus. But the virus doesn't directly destroy or infect B-cells. The issue is that the B-cells have trouble recognizing the components of the virus for which you would develop what's called a protective response.
When you vaccinate someone or when you get infected, the microbe is presenting itself to the immune system in a way that the immune system recognizes the important elements of the microbe and makes an immune response, both an antibody response and a cellular response, to ultimately contain the microbe. The components of HIV that the body's immune system would have to recognize in order to mount an effective immune response are virtually, in many respects, masked and unable to be seen by the immune system. So a person may get infected with HIV, but the immune system doesn't recognize the virus in a manner that elicits an ultimate protective immune response. So a successful HIV vaccine would require our doing something that is even better than what the body itself can do.
CBS CARES: In the press release for your presentation at the 2004 World AIDS Conference in Bangkok, you seemed to describe HIV as an immune activating disease?
DR. FAUCI: Right.
CBS CARES: Has there been a change in your thinking in that, until now, it seems that HIV has been viewed--at least in the U.S.--as an immune suppressive disease?
DR. FAUCI: No. Actually it's both and it's somewhat paradoxical. The ultimate effect of HIV is to suppress the body's immune system by destroying a very critical cellular component of the immune system, namely the CD4-positive T-cells.
But, one of the ways that HIV disrupts the immune system is by creating a state of aberrant or inappropriate immune activation in which the entire immune system is turned on. But because it's turned on in an inappropriate fashion, the ultimate effect turns out to be immuno-suppression as opposed to an appropriate specific immunological response.
CBS CARES: So, it's essentially an issue of timeline…some of the time HIV causes an overactive immune system and other times it results in immune suppression?
DR. FAUCI: It's a question of degree of activation and persistence of activation. When the immune system functions normally, it recognizes a foreign antigen. That could be a microbe. That could be a tumor. It could be something like that. Any of those things that are recognized as foreign.
And it ultimately turns itself on for a limited period of time, makes the appropriate specific response and then reverts back to its baseline, relatively resting state. That's the immune system functioning normally. If the constant bombardment of the virus turns on the immune system in a manner that's highly intense and highly persistent, it doesn't give the immune system room to respond in a normal manner to the stimulus that you're trying to protect against.
CBS CARES: Well, to the extent that HIV overactivates the immune system, do you see any role in the future for treating HIV patients in the U.S. with immune modulating or immune suppressive drugs like prednisone or cyclosporine?
DR. FAUCI: Well, those drugs have been tried, in various degrees, in animal models and even in human studies. So far, they have not been successful. However, I still think it's an open question that should be pursued as to whether or not we can selectively tone down the aberrant immune activation to the point where you get a beneficial effect, but not so much so that you suppress the immune system to the point of making matters even worse.
So you're walking a fine, delicate line when you're talking about immunosuppression or blunting immune activation as a therapeutic modality. It is something that, in principle, has some basis, but must be explored with great caution. And there are some clinical trials looking now at ways to blunt the aberrancy of the immune response without blunting the important components of the immune response that are necessary to contain the virus.
CBS CARES: We understand that NIH is experimenting with use of interleukin-2 in patients as a way to stimulate production of CD4 immune cells to replace those killed by HIV?
DR. FAUCI: That is correct.
CBS CARES: Since, as you explained earlier, the HIV virus has an affinity for attacking and destroying CD4 cells, is it possible that, by creating more CD4 cells through use of interleukin-2, the ultimate outcome could, ironically, be acceleration of HIV disease and, consequently, a weakened immune system?
DR. FAUCI: Conceivably, but that's the reason why interleukin-2 is generally administered simultaneously with medications that block the ability of the virus to replicate. So that you could get the best of both worlds where you're amplifying the immune system without necessarily turning on the virus replication. Because the virus replication is being held in check by the simultaneous administration of anti-retroviral therapy.
CBS CARES: Are these replacement CD4 immune cells, produced through use of interleukin, qualitatively as good as natural CD4 cells or is there a functional difference?
DR. FAUCI: Well, thus far, the ones that are produced appear to be functionally normal. The open question is would you have what we call the repertoire of the CD4 responses. Namely, the breadth of recognition capabilities. Is that going to ultimately be restored? And that's something that's under active study right now. But by all other measures, the CD4 cells appear to be relatively normal.
CBS CARES: NIH seems to have shown great interest in testing genetic profiles of HIV-positive patients through HLA typing. Can you please explain what HLA typing means and could this advance knowledge and treatment of HIV? For example, is it possible that new drugs or vaccines could be developed from what you learn?
DR. FAUCI: Well, it's probably more related to the nature of the immune response. An HLA typing is sort of a genetic profile. There are certain antigens that define what make me different from you from a genetic standpoint that relates to the immune system. HLA are molecules on cells that are important in the recognition and the ultimate triggering of an immune response.
There are certain genetic profiles that are more prone to one type of an immune response against a particular microbe versus another. And that's the reason why people with different HLA backgrounds have different responses and different propensities to a number of different diseases. What investigators are trying to do is to try and learn if there is any association between certain HLA profiles and the ability to contain the virus so that that could serve as an insight into how one might control the virus through immunological means, even in those people who don't possess a particular genetic background. So it's really a window into understanding the nature of a relatively protective immune response.
Page 1
Page 2
Page 3
Page 4
|
|
|
|
|
|
|
