AIDS/Dr. Anthony Fauci (NIH, 1984)

In our program, “AIDS: Acquired Immunodeficiency Syndrome,” a part of the Medicine for the Layman Series at the National Institutes of Health, we’ll take a closer look at the latest information on this new disease. [ Music ] In the public interest Primark presents the following special program as part of its ongoing dedication to enhancing healthcare education and delivery through its subsidiary, the Hospital Satellite Network. [ Music ] [Doctor Linda Reid:] Hello, I’m Doctor Linda Reid. Welcome to the Medicine for the Layman Series at the National Institutes of Health. Today we’re going to be listening to Doctor Anthony Fauci. He’s going to be talking about AIDS, the Acquired Immunodeficiency Syndrome. Doctor Fauci is with the National Institute of Infectious Diseases and Allergy. Let’s find out why some people came to the lecture. [Student:] I came because I’m a nursing student at George Mason University and I’m co-facilitating a seminar on AIDS
with a friend of mine. We came together. [Dr. Reid:] Have you found that you’ve been a victim of discrimination? [AIDS Patient:] [laughs] Definitely. I have definitely been a victim of discrimination. I was fired from my job. I have been refused housing. Some medical care has been refused, but not here at the National Institutes. [Dr. Reid:] Are you worried about the future? [AIDS Patient:] [laughs] Definitely. Definitely. Right now I’m… while I’m on a research protocol at the National Institutes of Health, the government is paying for me to live in a hotel and my medical costs are covered. However, as soon as my protocol runs out I have no apartment to go back to, I have no job to go back to, and I am very scared about what’s going to happen to me. [Dr. Reid:] We’ve seen how AIDS can gravely affect those who have it and those who are at risk for it. Now, let’s take a look at another aspect of AIDS, research. In our cover story tonight we’ll talk with a leading scientist about his work in AIDS research. [Narrator:] In this lab at the National Institutes of Health, the new illness that has attracted much media attention called Acquired Immune Deficiency Syndrome, or AIDS, is being carefully studied. Since the disease was first reported in the United States in mid-1981, scientists have been able to make some important breakthroughs in the discovery of what causes the disease. [Dr. Anthony Fauci:] Well, the most exciting breakthrough is unquestionably the fact that in just a few short years from the recognition that this disease exists, scientists have been able to identify and isolate the underlying cause, or etiologic agent. And AIDS is caused by HTLV3. [Narrator:] The Public Health Service has received reports of about 5,800 cases of AIDS with a case fatality ratio of 45 percent. Doctor Anthony Fauci is hopeful that the answer to this dreaded disease may be in sight. [Dr. Fauci:] I believe now that we have the agent in hand that the amount of effort and energy that’s being put into it by biomedical sciences, that within a reasonable period of time we’ll have a lot of these answers. [Dr. Reid:] Well, it’s certainly nice to know that the future looks brighter. Now, let’s go to the lecture and join Doctor Anthony Fauci as he talks about AIDS. [Dr. Fauci:] This evening what I’d like to do is discuss with you a topic which I’m sure all of you to a greater or lesser degree are aware of. It’s a topic that has occupied the interest and energy of a substantial proportion of the biomedical research community here at the NIH and throughout the country and the world, most recently, and that is the subject of the Acquired Immunodeficiency Syndrome. I’m working directly on AIDS, both clinically and from a basic science standpoint, but it gives me a great deal of pleasure and excitement to talk about AIDS, because it really is one of the few, or actually one of the only subjects, of all of the subjects that we tackle throughout the years, where you really have to change your lecture every month because of the extraordinary advances and evolution of this syndrome. That has provided a great challenge for the scientists involved in this and has provided, in many respects, hope for the individuals who are afflicted with this terrible syndrome. What I’d like to do this evening is to review for you some of the most recent advances in AIDS as well as provide for you a background for understanding how we got to where we are today in our understanding of AIDS. So what I’ll be discussing is some historical aspects of AIDS, the epidemiology, or as we say, the profile of the syndrome, how it came about, the populations that it afflicts. We’ll talk about some of the clinical manifestations, or how the disease expresses itself in the patient population. We can now talk about something that I couldn’t talk about just a few months ago, and that is the etiology of AIDS and how an understanding of the etiology has allowed us to make great advances, not only within the syndrome of AIDS, but also in a number of other diseases that have immunological components to them. And then finally we’ll talk some about the treatment and prevention of this syndrome. Now, first of all we must have a definition of AIDS. And I will tell you right off that the definition that is given, although it is a good definition, in fact it’s an excellent definition, it has some serious flaws. And the reason for the flaws are that it’s an empiric definition that is based on the secondary complications that someone will get, who has AIDS, and let me explain what I mean. First we’ll go through the definition. It’s the presence of pneumocystis carinii pneumonia, or other opportunistic infections, or Kaposi’s sarcoma. Now for those of you who aren’t used to hearing that terminology, what it is is the presence of the disease in an individual that you would not expect to see in someone who is otherwise normal immunologically. For example, if I said, “influenza” or “the common cold” or some other disease, you’d expect to see that in a normal population. In a population that does not have an immunological defect. But these diseases are present in individuals with AIDS but the most important component of this definition is that there’s an absence of a known cause of this underlying immune deficiency. In other words, they have a very severe defect in the mechanisms that protect them against these strange infections and against these tumors, which, one of which we’ll call Kaposi’s sarcoma. But we can’t figure out a reason why they have that defect. In other words, we didn’t give them any medications to get this defect. They don’t have any underlying tumors that might cause an immune defect. Now, for sure, this definition is going to change in the next several months or thereabouts, and the reason is that this definition does not account for the large number of individuals who have the immune defect, but have not yet gotten what we call the secondary complications; namely those infections or those tumors. For example, if I had AIDS…if I had the infection with the virus that causes AIDS, which we’ll talk about in a moment, but I hadn’t yet gotten an infection, by strict definition, from the Centers for Disease Control, I could not be classified as having AIDS. There are a lot of individuals that are out there that have the defect. The reason it’s important to recognize that is because the statistics that one sees regarding AIDS are based only on what I will call full-blown AIDS, and do not take into account the large number of individuals who have the defect already. Another very important aspect of this is that the transmissibility of the disease, you usually think of someone having AIDS transmitting the disease to someone else, when in fact, as I’ll discuss with you in a bit, the transmissibility might occur prior to the time that an individual develops one of these infections and is thereby classified as having AIDS. Now, now that we understand and appreciate and recognize the etiologic agent, and we’ll be developing tests for this, we might be able to better get a handle on the profile of this group of patients. [Music] Historically, we first recognized this disease actually as a new disease in 1981. The cases were first brought to the attention of the Centers for Disease Control, or the CDC, in 1979. In the summer of 1981 there were reports of unusual infections and/or tumors in otherwise healthy homosexual men. Now again, if I were giving you this lecture when we started working on AIDS a few years ago, I would be spending the first 10 minutes or so trying to convince the audience that we were dealing with a new disease. In fact, we don’t need to waste any time on that. This is a new disease, at least in the United States. Where it came from, we’ll discuss in a short while. But in the United States it’s new. And it’s very interesting and somewhat perplexing to have gone through, as an investigator, those early years in AIDS because when you’re dealing with a new syndrome like that and you don’t really understand it, anyone’s hypothesis about what this might be is held in equal respect to a well-thought out hypothesis. And I think that led to a lot of the misunderstanding, not only regarding AIDS in general, but regarding the entire homosexual population and how they may have been the early victims of this particular disease. And as I’m sure you’re all well-aware, there was an extraordinary amount of difficulty in that regard, particularly with the intensification of the already existing unfortunate discrimination against these individuals. I can remember in early, in the summer of 1981 when I first read in the report from the CDC of these cases of strange infections and tumors in patient, in male homosexuals in New York City area and in California, LA and San Francisco. I had thought initially that this might be a transmissible agent, but maybe it was some toxic substance, some drug or what have you, that they had ingested, but then when it became clear that such a large number of individuals, on both coasts, were getting it, we became rather suspicious that we were dealing with an infectious agent. And then as soon as the IV drug users became infected, and then hemophiliacs, with the common denominator of the possibility of blood-borne transmission in addition to sexual transmission, then it became clear that we were dealing with a very special, unprecedented situation, which we’ll have the opportunity to go through with you. [Music] What do we mean by risk groups? The risk groups are those individuals who, because of the epidemiology or the profile of the disease, appear to be at a particular risk of getting the disease. Now, if one looks at the profile in the United States, 71 or more percent of the individuals with this full-blown AIDS now are homosexual or bisexual men. Seventeen and a half percent of them are intravenous drug users. Four percent are Haitian. A little less than one percent are hemophiliacs, and about six percent of them don’t fall into any of the known above risk groups. This number is much less now because there’s been an expansion of the risk groups, which are related to now our understanding of the etiology and transmissibility of this disease. I’ll get to in some of the later slides how this disease, which we surmised early on,
started off in the male homosexual population in this country, not that there was anything intrinsically different or wrong or what have you about homosexuality, it was very simple; it’s straightforward epidemiology. You take an infectious agent and you introduce it into a population in which the spread among those individuals, if it’s sexual-contact spread, it’s a perfect setup to spread. In any event, what we had was a concentration of cases, as you’ll see here, in the New York Metropolitan Area , New York City and New Jersey, and in Los Angeles and San Francisco in California. Some of the data that I’ll be showing you now is based on the first 4,000 cases of AIDS in this country. Right now, in October of 1984, there are greater than 6,000 documented cases of full-blown AIDS in the United States. Now, this color diagram, with the darker areas being the most intense areas with regard to the populations involved, as you can see, now it’s spread into most of the states in the United States. As a matter of fact, it has spread throughout the world. But the earlier concentration in New York and California again merely reflected that since the majority of the patients at that time were male homosexuals, there is a great concentration of what has been called “fast-lane” homosexuals, and I’ll explain what I mean by that in a moment, here in New York City and in the two cities in California. “Fast-lane” is an unfortunate term that’s used to designate a large amount, or a great degree, of sexual contact, meaning large numbers of sexual partners, in many cases anonymous sexual partners. Now, people kind of get hung up on that with regard to the concept of homosexuality. And that’s unfortunate because all that is telling us is that if someone has multiple sexual contacts, and has a sexually-transmitted disease, that disease will spread within that population, and that’s exactly what we were seeing. And as you can see the breakdown of New York, San Francisco, Miami, etc. is right there. At the time that the disease was first recognized, we had no idea that this was a viral agent that was introduced into the population. So investigators, particularly the Centers for Disease Control, the CDC, tried to collect a wide range of epidemiologic data, namely, what is the profile of these patients? And the information merely bounced back as telling us what the profile of the risk groups were. For example, at the time this data was collected, we knew that the majority were male homosexuals, but there was a rather substantial group that were IV drug users. And if one looks at race/ethnicity, the reason we broke it down into race/ethnicity, we wanted to determine if there was any factor, genetic or otherwise, which would predispose someone to AIDS. As you can see, about 58 percent of the individuals were white, non-Hispanic. If you did a profile of the male homosexuals in New York and California, the majority of them would be white, non-Hispanics. There was a lesser group that were black, non-Hispanics and others were Hispanics. If you look at the IV drug users in those major cities, the majority of them would be blacks and Hispanics. So all we were seeing were profiles of the risk groups. The same held true if we tried to break them down by age. Most of the individuals were seen between the 20 and 49 year age group. All that told us is that is exactly the age group where most of the actively practicing male homosexual population in this country is. Again, merely a reflection of the epidemiology of the risk group, and didn’t really tell us much about the disease. Now, what about transmissibility of AIDS? Again, I need not go into the data explaining why we know now for sure that a) this is a new agent, and b) this agent is transmitted by sexual contact and by blood or blood products. Now, I suggested the hypothesis to you a few minutes ago that the disease started off in this country within the male homosexual population, and that’s exactly what happened. There are some theories of how it got introduced into the male homosexual population. If that is the case, which indeed it is, then the transmissibility will relate to the contacts within the male homosexual population as well as the overlap between the male homosexual population and other populations that became risk groups. And now that’s very clearly seen. Now, you keep getting asked, why the male homosexual population? Well, as I mentioned, for reasons that will become clear shortly, the virus was introduced into the population, and it’s a sexually transmitted disease. Therefore sexual contact spreads the disease. Since male homosexual individuals almost invariably, not always, confine their homosexual activities, or their sexual activities, to other male homosexuals, what you are going to have is a compounding and a spread within that group. There’s nothing intrinsic about homosexuality that would make them susceptible to the disease. If you want to create an analogy, let us say that this disease was transmitted by sneezing, which it is not, it is clearly not transmitted that way, then if you had the disease introduced into schoolchildren, schoolchildren would have it in a rampant form because they sneeze all over each other. Not to mention, people who ride the subways and elevators and things like that. That’s not the way this disease is spread. It is spread by sexual transmission and it was introduced into a population in which sexual contact is rather substantial with regard to numbers. The same thing holds true for blood or blood product, it can be transmitted by blood or blood products. So what is the link then with how the disease got out of the homosexual population into other risk groups? This is diagramed here on this slide because if you look at the male homosexual population, a proportion of them, a small proportion, but nonetheless a proportion of them, overlap with intravenous drug users. Since this is a virus, and the virus can go by bloodborne transmission now from the homosexual group to the needles of IV drug users. Hence you now have it in IV drug users who spread it among themselves by sharing the needle, which is contaminated by this virus. We know that individuals can be walking around carrying the virus and not know it. They give blood transfusions. They give blood products that will ultimately be, later they are transformed into plasma products to be given to the hemophiliacs, who need those clotting factors to reconstitute their deficient clotting. Hence the disease can then overlap into the hemophiliac population. And as I’m going to show you in a moment, that risk group, of the four major risk groups, has expanded some for the reasons which I have just explained, namely contact between the original risk groups and other risk groups, which have now accumulated. And on this slide what we have is what we’ll call the expanded risk groups. We’ve spoken about the first, the second, the third, and the fourth. Now, the Haitian situation has created some controversy in this country, and the reason is that we have, public health officials have designated the Haitians as a separate risk group. Now, the objection to that and it’s a reasonable objection is that discriminates against Haitians. Why should you call the Haitians a separate risk group? We call them a separate risk group because only a very small percentage of the Haitian population, their AIDS can be explained by homosexual activity or IV drug use. So there’s something else going on there and we’ll get to that when we talk about what we’re calling now, the African connection. Transfusion related; again the disease is clearly transmitted from transfusions. Does that mean you should feel unsafe about getting a transfusion? No. Because the risk is so small that the chances of getting AIDS from a transfusion are less than the chances of somebody mixing up the blood and giving you the wrong blood and you’re winding up with a transfusion reaction and dying from it. So, the fact is, from an epidemiological standpoint we must be aware of that, but the risk is not great. So the fear of getting a blood transfusion is unwarranted. Female sexual partners of AIDS patients, or persons at risk for AIDS; a very important clue of the profile of that disease in this country, because the female sexual partners of bisexual males or of IV drug users have gotten the disease. What we haven’t seen, and it is probably the reason why this disease has not spread rampantly into other risk groups, is that we’re not seeing what we call back-transmission, or transmission from a woman back to a man, and that has an important implication that is different from what we’re seeing, as I’ll mention shortly in the African connection. Now, children in households of AIDS patients, we’ll get back to that in a moment. Certain black Africans, such as those in Chad, Zaire, etc. and persons in none of the above risk groups; this number nine is really rather small. Let’s take a look at some of these risk groups. Can it be transmitted by blood transfusions? Clearly we have documented a significant number of cases of transfusion-related AIDS. In other words, someone who was carrying the virus donated blood and that whole blood or blood products were then transfused into an individual who was not in any of the other risk groups. That individual two years, three years, and even as late as four or five years, comes down with AIDS. The question, that’s very interesting and important, is that blood was given to a large number of individuals. Why does only maybe one or two come down with AIDS? And the reason for that is probably related to what we call co-factors, or there are intrinsic or innate susceptibility to getting AIDS, which if you don’t have that, even if you’re exposed to the agent, you won’t get it. In essence, AIDS is a difficult disease to catch. It definitely is a difficult disease to catch. We know how it’s transmitted, but you can be exposed to that agent and not at all get the disease. Moving on then to other possibilities: what about heterosexual contact? I gave you the example of the heterosexual female partner of a male with AIDS. Heterosexual contact indeed is one of the major modes of transmission, for example in Africa. That’s different than in the United States. We don’t know why if a woman has AIDS in the U.S. population she will, at least by the data so far, not transmit the disease back to her male heterosexual partner. Now, there is a lot of hypothesis of why that is so, and again, we don’t know for sure. But one of the possibilities is that the disease, although it’s sexually transmitted, needs to enter into the bloodstream. Now, from heterosexual contact, from vaginal intercourse, it is unlikely that the agent can break through the vaginal mucosa. But that is not the case if one thinks for example of the anal intercourse that is the common practice in the homosexual population, which may be one of the reasons why those, that the small rents or tears in rectal mucosa may be a perfect entry site for the virus. Again, these are things that you’ll read about and that you’ll hear about. The proof of that is not really well-established. AIDS in infants. Now, you might remember some time ago when the newspapers broke that AIDS was seen in infants in households of an individual at risk for AIDS or who had AIDS. It was that which brought to focus the possibility and the conjecture on the part of the lay-press that perhaps AIDS could be spread by casual contact, namely by having an infant or a child in a home being rocked or put on the knee of an uncle who was an IV drug user and in fact was harboring the virus. That was very unfortunate because what that led to was a fear that maybe it was transmitted by casual contact. We know now, from the work of Bob Gallo and his colleagues, that if you examine the infants with AIDS, and their mothers, the mother in three out of four cases has the virus in an asymptomatic way. In other words, the child did not get it from casual contact or even close, intimate contact that you would give to a baby. The child got it either intrauterinely or perinatally because the mother had the virus. So that brings us then to a question that is very important and that is asked constantly of me and my colleagues in this area. Can AIDS be transmitted by casual contact? And we’ve learned to never say never and never say always in medicine, but we’ve also learned to look at the scientific data and the scientific data is overwhelming that in fact AIDS cannot be transmitted by casual contact. In other words, a waiter, someone in the elevator, someone sneezing on you, or even someone embracing you or hugging you or holding your hand is not going to transmit AIDS. So the fear of individuals who either have AIDS or are at risk group for AIDS transmitting AIDS is an understandable fear, but really might translate into uncalled-for discrimination, which unfortunately has been the case. And that’s an issue that I really must emphasize over and over again; that there is no scientific evidence at all that it can be transmitted by casual contact. Now, what about the geographic origin of AIDS? What I’m going to tell you in the next couple of minutes and in this next two slides
is scientific data, and I’ll tell you with the data, and then some speculation. The scientific data is that AIDS exists in Africa, in central Africa, particularly in Zaire. It exists in a rather substantial way. The incidence of AIDS in Zaire is as great as it is, per 100,0000 population, as it is in San Francisco. If one does epidemiologic study by examining the sera of individuals in Africa, we know that the disease existed there in the early 70s, before it existed in the United States. Is then central Africa the source or the origin of AIDS in the United States? I don’t know that. Now we’re talking about hypothesis. Let me tell you another fact. In the late ’60s and early ’70s, thousands, not a few, but thousands, of Haitians came to Zaire, particularly in Kinshasa, the capital, to work as technical advisers for the Zairian government. After several years there, because of the nationalization of much of the industry, they were essentially kicked out of Zaire and came back to Haiti, to the United States, and to Canada. Is that a possible connection? The answer is yes, because it is very likely that the male homosexuals in New York City, who frequently travel to Port au Prince in Haiti for vacations and for sexual contacts down there, picked up the virus in Haiti and then, because of the mobility of the population between New York and the West Coast, there was spread back and forth from the West Coast. In addition, the early cases in Europe, in France, the early cases in England and in Germany, can be clearly traced to homosexual contacts from individuals who resided in New York. But there’s also a very important clue there because most of the cases in Belgium in fact were among black Africans who had come from Zaire and had gone to Belgium for medical assistance. As you probably know, Zaire was formerly the Belgian Congo. So there’s a great deal of link between Belgium and Zaire. That was the first clue that perhaps the disease might have originated there. So we don’t know really scientifically where it originated, but a series of circumstantial happenings strongly suggest that this may have been the original focus and how it happened to get introduced into the male homosexual population. [Music] What about the clinical manifestations of AIDS? In other words, what happens to individuals who get full-blown AIDS? Well, first of all there are what we call opportunistic infections, and I’ll explain that in a moment. Then there is tumors called Kaposi’s sarcoma, which we’ll explain. There’s an interesting syndrome called chronic lymphadenopathy. There are certain other tumors and there are what we call autoimmune phenomenon, which merely reflect an aberrancy of the body’s immune system. What do we mean when we say opportunistic infection? An opportunistic infection is an infection which occurs in a person whose defense mechanisms are impaired, hence the microorganism uses the opportunity to invade the person because of the weakened defenses. In other words, it takes the opportunity, hence it is an opportunistic infection. You wouldn’t expect to see that infection in individuals who have normal immunity. And here are some of these opportunistic infections. They have very strange names that I’m not going to run through, but I’m going to give you some examples of them. It’s important to realize that these were big, red flags for us early on in our study of AIDS, because you would not expect an otherwise healthy individual, like a healthy young homosexual man, to get any of these things unless something was very, very wrong with his immune system. The first is a particular type of pneumonia, which is called pneumocystis carinii pneumonia, which is caused by a protozoa organism that is ubiquitous, it is all over, it’s in my lung. The reason I don’t have pneumocystis carinii pneumonia, because my defense mechanisms are keeping that organism in check. If I were to take drugs that would markedly immunosuppress me, there would be a reasonably good chance that I would get that pneumonia. That’s what happens to the AIDS individuals, as I’ll show you when we talk about immunology. They’re substantially immunosuppressed. What about this microorganism? It’s called mycobacterium avium intracellulare, again a bizarre illness. I have been doing infectious disease consults in this building for the last 16 and a half years and I have seen one case of mycobacterium avium intracellulare in cancer patients who we immunosuppressed with chemotherapy. We see it all the time now in our patients with AIDS. Here’s an individual who has oral thrush, or candida, in the mucosal membrane of their mouth. It can also affect the esophagus. This is an x-ray of an esophagus in which we poured dye down the esophagus, and what you see, it’s difficult if you haven’t read these before, but this should be a very smooth surface because your esophagus is very smooth, which allows the food to go down there in an almost imperceptible way. Here are what we call scalloping of the esophagus. That’s due to the invasion of the mucosa by the candida microorganism. And also there’s a disease called cytomegalovirus, which is a virus that isn’t the cause of AIDS, but it’s one of those opportunistic infections that comes in and attacks an individual. And here is a photograph of the eye of a patient of mine with AIDS, which as you can see is what we call chewed up. And I’ll show you what we mean by that when one compares it with a normal retina. See the smoothness and the easy ability to look at the blood vessel. This is what it looks like in an AIDS patient. The virus has infiltrated the cells of the retina. What about tumors in AIDS? Well, Kaposi’s sarcoma we’ll explain in a moment, and diffuse undifferentiated Hodgkin’s lymphoma. Now what do I mean by that? All that means is that there’s a particular type of a tumor of a particular type of a cell that is seen in these individuals with AIDS. These are the typical skin lesions of Kaposi’s sarcoma. Now, what is Kaposi’s sarcoma? It’s a tumor of those cells which make up blood vessels. What we call them, endothelial cells. The disease is usually confined to the skin, but in AIDS patients it spreads to all organs of the body. Ten percent of Kaposi’s sarcoma in non-AIDS patients spreads elsewhere. 75 percent of AIDS patients who have Kaposi’s
will have spread if you do not check the disease, and this, Kaposi’s can really come in very strange places. Here it is in the eyelid of an individual. There is a syndrome that’s related to AIDS called chronic lymphadenopathy. And all that is is swelling of the lymph glands, either in the groin, in the axilla, in the neck or cervical area. If I were giving this lecture eight months ago I would have a slide that had a question: what is the relationship of chronic lymphadenopathy to AIDS? Is it related? Well, we now know from virus isolation that greater than 85 percent of individuals with this syndrome have the virus in them. The real question that we don’t know the answer to now, in October of 1984, is what proportion of those individuals will ultimately go on to develop AIDS. The key, or the secret, to protection against full-blown AIDS may be in these chronic lymphadenopathy patients. In other words, why aren’t they all getting AIDS? We’re studying these individuals to try and determine what component of their immune response is keeping the AIDS virus in check. We do know, with regard to my question of the relationship of persistent lymphadenopathy to AIDS, that from 2.5 to 17 to 19 percent of those individuals, over a two to three year period, will develop AIDS. We don’t know what the five and ten year figure will be. Now, what about the fatality of this disease, before we get onto the etiology and immunology. The number that is given by the Centers for Disease Control, is approximately 43 percent of all the patients. But if you break them down from individuals who were diagnosed in 1979 and look up to the point of individuals who were diagnosed this year, one can see that there are very few, if any, individuals still alive who had the disease back in 1979. Obviously there are a large number here, 80 percent of them are alive, who were diagnosed in 1984. Right now, the ultimate mortality of someone who has full-blown AIDS, namely already has the secondary complications, might approach 100 percent. Now, when you say that, you go now, “Wait a minute, there are a lot of people out there who have AIDS. Are they all going to die?” The answer to that is we don’t know. But that’s the way the research is going now. That is the reason why we are furiously looking at means, be them direct attack on the virus itself, or attempt to reconstitute the immune response with various factors, such that we can curb this very high fatality rate and we won’t have 100 percent mortality, and we have a lot of hope that in fact, given the work that’s going on now, we might see a realization of that hope in some time, hopefully very soon. [Music] What about the etiology of AIDS? I’ve been alluding throughout this entire discussion to this virus that causes AIDS. What about this virus? What is it? I’m sure you’ve heard about it in the paper. We call it the human T-cell leukemia lymphoma virus, or HTLV3. And the reason we call it that was that a few years ago Bob Gallo, from the Cancer Institute here at the NIH, had discovered that a virus, a retrovirus, as we call it, and that’s what it is, a retrovirus because it has a particular type of an enzyme in it, which gives you a reversal of the usual genetic process of propagating itself, was causing this HTLV1, was causing adult t-cell lymphomas and leukemias that were endemic in Japan, in the Caribbean, and in certain southeastern states of the United States. In fact, a variant of this HTLV1, which we’ve been calling HTLV3, is in fact the etiologic agent of AIDS. An agent was discovered in France, which the French call lymphadenopathy-associated virus, or LAV. It’s the same thing as HTLV3. So the virus in Europe, in Africa, in the United States is the same. Here is a schematic diagram showing you that this virus has a propensity to attack a particular type of cell. That’s a really, truly critical point because before we knew what the virus was, the only thing we knew was that our patients had a selected defect of a particular type of a cell. And it was a T-helper cell. I’m going to explain what I mean by that in a moment. That was the clue for the individuals who were doing the virology to look for a virus that infected T4 cells, or helper cells. Now, we already knew from Gallo’s work that lymphoproliferative, or adult t-cell leukemia, was caused by this virus, so therefore a major effort was directed at determining if a variant of this virus could actually cause depletion of lymphocytes, or acquired immunodeficiency syndrome. And as it turned out, a variant of that virus, in fact, caused the syndrome. We have to understand some basic fundamentals about the immune system. There are major components of the immune system. There are cells called B cells. We call it B because it’s bone marrow derived, or bursa-equivalent. It’s a technical term that merely connotes that this cell has a certain derivation, but its function is what’s important. It makes the antibodies, those proteins that attack microorganisms. B cells produce antibodies. We need them for our defenses. In addition to B cells there’s a very interesting kind of cell called a helper cell. The reason we call it a helper cell, it is because it is responsible for helping, not only this B cell but all other cells, perform their function. It’s the catalyst that makes the immune system go. It’s the focal cell that orchestrates the immune system, this T-cell. It’s called T because it’s derived from the thymus gland. And it is a T4 cell because it has a designation of a monoclonal antibody that can recognize it, or some technique that we use to identify it, and it has inducer or helper function. In addition to balancing immune response, we have suppressor cells, which can actually dampen down the immune system. So we have B cells making the antibodies, T-cell doing the orchestration, suppressor cells keeping the lid on things so that the immune system doesn’t run away with itself. When it does, as a matter of fact, that’s how you get autoimmune disease, which is a different topic that we don’t have time to discuss this evening. With that as a very basic background of the immune system, how does HTLV3 affect these human t-cells? Well, it selectively infects the t-cell. It has hat we call a tropism for it. If you put a lot of cells in the tube and you throw in HTLV3 it’ll go right for that T4 cell and infect it. It has an affinity for the helper cell. It seems to leave the suppressor cell alone and it damages, but does not immediately kill the cell, but ultimately depletes the cell. This T4 cell, as I alluded to earlier, is the critical cell. What it does is that it’s responsible in a direct or indirect way for virtually everything the immune system does. It induces suppressor cells. It induces killer cells. You don’t have to remember all this, just merely get the concept that if, teleologically, I wanted to pick out the one cell that if I damaged that cell I would do the most damage to the immune system I, as an immunologist, would pick out the T4 cell. That’s exactly what this virus did. It picked out the T4 cell and it created a tremendous amount of damage in the immune system. Now, in the peripheral blood of man, about 60 percent of the cells are helper cells and about 30 percent of them are suppressor cells. What happens in AIDS is that we start losing these helper cells. And if you look at the profile immunologically of any of my AIDS patients, what you’ll see is that they’re markedly deficient in their T4 or helper cells. Now, the immunological abnormalities in AIDS. First of all, as I mentioned just now, there’s a quantitative t-cell defect. Now, I can’t expect anybody except an immunologist in the audience to be able to understand what this profile is, but there’s something in it that I chose to show you, even if you don’t understand immunology. This is a computerized technique of writing out the amount of cells that an individual has in their blood. This is the background, as you can see there’s nothing there. This is the T4 blip on the computer of the helper cells in the normal, healthy individual, who is the identical twin, by the way, of this patient with AIDS. If you look at the AIDS patient, this individual has virtually no helper cells. The suppressor cells are normal, normal blip in each individual, the normal individual and the individual with AIDS. There’s a functional t-cell defect. In other words, this helper cell here, which I’ve schematically diagrammed as being infected with this HTLV3, generally tells this B cell what to do, tells some of the other cells what to do, usually there are about two of these to every one of these. What happens in AIDS? These get depleted and these fellows take over. What else do we see in AIDS? There’s a B cell hyperactivity. In other words, there’s factors likely that are released by this infected t-cell, which trigger that B cell. In addition, the B cell itself, we know now, might be susceptible under certain circumstances to infection with this HTLV3. What does that mean with regard to the patient’s ability to respond to a particular stimulus? That is suppressed because the B cell, which is supposed to recognize these foreign antigens, doesn’t do it anymore because it’s remarkably weakened because it has been, one, either infected with the virus, or, as I mentioned earlier, it requires a good healthy t-cell to kind of push it to do what it wants to do. What it needs is help from the t-cell. That’s why we call it a helper t-cell. But the helper t-cells are gone in this patient. So the B cell cannot respond well, another insult to the immune system. Also the monocyte, which is a cell that’s responsible for killing a lot of infections. This is blocked in AIDS patients. How can that be? Well, by a number of mechanisms. This T-helper cell–here he comes again–that cell is responsible for telling the monocyte what to do. If I get infected; for example I made the analogy of the pneumocystis carinii pneumonia in my lung. Why aren’t I getting pneumocystis pneumonia? Because my T-cells are telling my monocyte to make sure that those pneumocysts don’t grow very much. Now, if I don’t have those t-cells, the monocyte’s not gonna know that and I’m gonna get pneumocystis carinii pneumonia. That’s exactly what’s happening in AIDS. In addition, in our body, there are a number of cells, which we call killer cells, that are responsible for killing either virus-infected targets or tumor cells. They’re our way of surveilling. They look around. They want to see if there’s a virus around. If there is, they attack it. They look around to see if there’s a tumor around. They attack it. The same problem exists. These cells don’t do very well unless that T4 helper cell is prodding them on. So although we have normal numbers of these cells, they’re not hearing any information. They’re not getting marching orders from the T4 cell. So what this slide here does is that it essentially summarizes how this focal cell here, which is infected with the deadly virus, is responsible for the activity of almost all of the other cells that have something to do with immunity in our body. For example, the B cell, as I mentioned, just to review for you, the B cell cannot do any of the things it’s supposed to do. The monocyte macrophage can’t kill because it’s not getting the signal. The T4 induction of other cells, such as the natural killer cell, they don’t work right. Other T4 cells, which are supposed to do other things immunologically, don’t work right. Other cell types such as suppressor cells, in other words, this hypothetical scheme, which is no more hypothesis, explains the apparent paradox of the immune defect. What is that paradox? You have one cell that’s infected specifically with a virus that has a given function. And yet, when you look at the immune system it is globally wiped out. So how can one cell cause a global wipeout of a system that’s made up of so many different cells? And the reason is that those different cells are critically dependent upon that one cell that’s the victim of the virus. Now, what about the treatment and prevention of AIDS? That is a very difficult problem. Prevention by public health awareness of contact; the male homosexual community has responded in a most encouraging and extraordinary way of educating themselves and their brethren about the dangers of certain types of contacts, of anonymous contacts, and preventing the spread among themselves. That is an important point. We’ll get to in a moment vaccination, which is a potential, a real potential, for prevention of this disease. What have we been doing and what have been some of the very discouraging results, which although they are in and of themselves discouraging, have nonetheless provided information which we feel will be the foundation for investigation, which we hope and believe deep down will not be as discouraging as we have experienced in the past. First of all what you have to do is you have to treat the opportunistic infections and/or Kaposi’s sarcoma. We’re doing that. We tried immunological reconstitution with bone marrow transplants and lymphocyte transfusion. It did not work. Why didn’t it work? It did not work because the virus was still in the individual. Immunological enhancement. We’re now trying factors that are made by the lymphocytes, giving them to individuals for a number of reasons to try and boost up their immune response to perhaps curtail the virus in a way that we don’t think will completely eliminate it, but curtail it enough so that when we develop an agent that has specific activity against the virus, namely something that can kill the HTLV3, then we can combine that with these reconstitution experiments, which will hopefully no longer be experiments, but will be common practice. And those two things together might then rid individuals who are already infected with the virus by a combination of killing the virus and reconstituting the immune response. And finally, as you I’m sure have read in the papers, given the fact that we now have the virus in our hands, it is quite possible, in fact it’s invariable, that we will develop a vaccine for AIDS. The question that remains to be answered is will that vaccine be effective in protecting individuals against infection with the virus? And we don’t know that, but that’s exactly where much of the research is going on at the present time. In summary then, we have discussed the broad implications, clinically and otherwise, of the Acquired Immunodeficiency Syndrome, AIDS. We know now that it is caused by an infectious agent, that it’s a transmissible disease, and that it works its damaging effects by specifically modulating in a negative way the immune system. We don’t know a lot about AIDS but we also know an incredible amount about it from our experience over the past three or four years, and hopefully our recent advances of being able to isolate, identify, and characterize the agent, together with the advances in understanding the natural history and pathophysiology of this disease, will allow us over the next year to come back to you and tell you that we now not only have hope and hypothesis, but that we have a real prevention and indeed a real cure. Thank you. [ Applause ] [Dr. Reid:] Let’s recap the most important points from the lecture. Thank you for joining us. I’m Doctor Linda Reid for the Hospital Satellite Network. [Music] [Chime] [Narrator:] The preceding program has been a presentation of the Hospital Satellite Network. [Chime]

5 thoughts on “AIDS/Dr. Anthony Fauci (NIH, 1984)


  2. As someone who has been working in this field for the last 10+ years, it's really incredible to see what was already known in 1983 and how fast researchers were able to figure this out. Dr. Fauci, as usual, has done an outstanding job explaining this complex topic. This was really a pleasure to watch and, seeing how far we've come and how much we've learned, I feel very hopeful about the progress to come towards an AIDS-free future.

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