Dr. James Curran on 30 Years of AIDS

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bjbj In 1981, I was chief of the research branch of the STD Control Division at the CDC. And we were studying gonorrhea complications, chlamydia, infertility, but also hepatitis B transmission among gay men. And we were working with the hepatitis division at CDC on a vaccine trial on gay men in five cities in the United States. We learned in late May 1981 that there were several requests for pentamidine isethionate, a drug to treat pneumocystis pneumonia, and distributed by the CDC, from doctors in California and New York. Dr. Michael Gottlieb, from UCLA at the time, worked with Wayne Shandera, an epidemic intelligence service officer in Los Angeles, to summarize the five cases that they had seen in that metropolitan area for a report in MMWR. I received the draft of the article because we d been working with gay men and STDs the week before it was to be published. Along with my other colleagues in STD research, we were floored that previously-healthy gay men were dying, or nearly dying, from such a rare infection, an infection which is usually a scavenger among people whose immune systems are compromised. Of course, from our point of view, from our STD lens, we immediately thought that this could be something related to sexual behavior and sexual transmission. When the first MMWR article was about to be published, the CDC called together a group of scientists, investigators, and administrators, and we formed a task force. And I was asked to chair the taskforce for the initial investigations. I was detailed initially for three months to head this group. The first thing that we did was develop a case definition for surveillance purposes. And then we deployed physicians and epidemiologists to all of the major cities of the country in search of cases. We also worked closely with state and local health departments to do this. And then, of course, by publishing the articles quickly, we were calling for additional cases reports. We were concerned to find out whether this was a new phenomenon or simply one that was newly recognized, and whether it was increasing in frequency and who was really affected. Was it truly all men? Was it truly all gay men? Were women also affected? Children? Was it occurring elsewhere than within the United States? Was it occurring in additional states? And so investigations could not be limited to a single group nor could it be limited to a single country or a single part of the country. So it was important not to presuppose that we knew what the distribution of cases were. It was important to come up with a definition which could be applied universally. And the definition was adopted throughout the world almost immediately. The case definition was very specific. It required a biopsy either for the infections or some other positive identification of serious or fatal opportunistic infections, or this rare cancer, Kaposi s sarcoma, that had been reported in young men. It also required a biopsy. We sent physicians to the 18 largest cities in the country to go through records going back five years, and we reviewed our own reports, and made many, many calls to public health officials, infectious disease doctors and cancer doctors within the country. Following a rapid deployment of the case definition, we did surveillance in New York and California and elsewhere, and came up with a follow-up report about one month later of cases of Kaposi s sarcoma and additional fatal opportunistic infections from New York and California. The Kaposi s sarcoma was an important clue because it had been seen as an opportunistic cancer in people with transplants, people who are on immunosuppressive therapy, and in severely malnourished infants in Africa, from studies done by the National Cancer Institute in Uganda. So there was some clue that Kaposi s sarcoma itself seemed to be an opportunistic cancer. And that tied together an epidemic of immune suppression, rather than an epidemic of infection or cancer. It became quite clear that immune suppression was central to what was being seen. What was unclear was what was causing the immune suppression, and whether the immune suppression itself was central to the condition, whether it was acquired -- it seemed to be acquired--and what was causing it. Many of us at the CDC who had worked on sexually transmitted diseases, and particularly hepatitis B among gay men, saw a model of a virus which was transmitted like hepatitis B, through sexual contact, through injecting drugs, or through transfusions as a model which best fit the epidemic. Whether this was a new virus or an altered virus, for example perhaps an altered cytomegalovirus, or whether it represented viral overload from multiple viruses was unclear at the time. But there were many people with other hypotheses, environmental hypotheses and others that were competing for time, and it was important to keep an open mind. I mean, for example, what if this were due to a drug? What if there was an external stimulus, perhaps isobutyl nitrite or amyl nitrite, one of the original concerns that these drugs had been used for recreational purposes by a select group of gay men. Wouldn t that have been wonderful? And wouldn t it have been awful to miss something that could have simply been removed from the environment and prevent all future cases. I think throughout the country and throughout the world, we thought that the most important thing was to find out what was causing AIDS, and to do everything we could do to prevent it. Most of us at the CDC felt that it was probably caused by a new virus, but we were certainly open to anything that could have been the cause. I think the most important contribution in retrospect that the CDC made in terms of finding the cause of AIDS was convincing people that the epidemiologic pattern was true. And the case definition was highly specific. It took only cases which fit a rather narrow definition, with very specific means of diagnosis that had to be biopsy-confirmed. And they were such unusual cases that when the pattern went from gay men to injecting drug users and then finally to persons with hemophilia, there could really only be in a unifying hypothesis, a viral agent that could be transmitted through a variety of means. And this was very convincing to the scientists of the world who were looking for the cause. And that would drive them to search for such an infectious agent. We had hoped that if this was caused by a virus, it would have a natural history something like Hepatitis B, where people would be infected by the virus, and then they would have -- many would have a successful immune response and would then become immune to future infections. This is a pattern of many viruses. But there could be some people who have fulminant course who we were seeing as cases of AIDS that was often failing. We described the situation, because many doctors were seeing people with swollen lymph nodes, with thrombocytopenia, with other kind of milder conditions, which seemed to go away often. They would wax and wane. We describe this as the bottom of the iceberg, the base of the iceberg. With the cases of AIDS, it is the tip of the iceberg. And most of us were hoping that the bottom of the iceberg would be a much larger number of people who successfully battle the infection and who, importantly, would provide us with clues to develop a vaccine to save the others. I think the next thing that happened was that when the epidemiologic pattern was absolutely clear that this was caused by a transmissible virus. And I would say that that most convincing evidence were the cases in persons with hemophilia, who had received untreated blood products that had been pooled from hundreds of thousands of donors per year. That provided absolutely compelling evidence to everyone that this was something that was not only transmittable sexually, but could be transmitted in the blood supply. So on the one hand, we went from complacency and denial to panic. Can I get this from receiving blood or donating blood? If this is caused by a virus, may I get it by taking care of patients who have it, or by handling lab specimens from people who have it? Or will I get it by being next door and having dinner with somebody? So this gave us the opportunity, as well as the obligation, to do our best to craft prevention recommendations. The first ones were drafted by the CDC in late 1982. And they were advice for clinical and laboratory workers dealing with AIDS. Again, a year before the virus was discovered, there was advice on how people could prevent themselves from becoming affected and infected with the putative virus. And they were designed very much like recommendations for Hepatitis B precautions. And these precautions allowed people to work safely. The best advice we could. But also not to shun the patients or shun the work, because that was so important. In early 1983, the CDC drafted recommendations for the entire U.S. Public Health Service that were published in March 1983 in the MMWR. And these recommendations were recommendations against blood donation by groups that were highly affected by AIDS, recommendations on reducing partners and avoiding sexual contact with people who had AIDS, recommendations on blood donation and for the first time, autologous blood donation, to reduce the number of donations. And these recommendations actually look pretty good today even though they were made before the virus was discovered. The recommendations were picked up, not only by the World Health Organization, but also the AMA, gay physicians groups, the American Association of Blood Banks, the American Red Cross, and others. Again, the recommendations were made on epidemiologic observations before the virus was discovered. The setting in 1981 in the United States was that we had fairly high unemployment and inflation. Ronald Reagan had just been elected president and was concerned about reducing the domestic budget. So there were very severe fiscal constraints throughout the Public Health Service. Despite that, the Centers for Disease Control has always been known for its capacity to respond to public health emergencies. And that capacity attracts the type of people who are energized and motivated by new problems. So we had an enormous amount of internal energy without any money. So we couldn't -- we had trouble with travel budgets, we had trouble with supporting our colleagues in the community. But we had a lot of eager people who were able to work and willing to work many, many hours per week. Our taskforce probably averaged 80 hours per week, in terms of people. And we were energized and motivated by the severity of the problem and the newness of it, that this was obviously something new and it was something which was quite serious that deserved our attention. During the first three years of AIDS, from 1981 to 1984, at the CDC we were charged with recording the status of the epidemic. And we were always aware that the cases were growing very fast and being reported. We began by saying they were doubling every six months. And they continued to double every six months, which of course leads to very large numbers over time. And we were telling people that this was the tip of the iceberg, that there were many more people affected. Often we were accused of exaggerating the problem, calling too much attention to a problem which we felt was being ignored. In fact, each time that we would estimate the size of the problem, we were really underestimating it, while we were being accused of overestimating and exaggerating it. Before the virus was discovered, I was saying that there may be hundreds of thousands of people affected with whatever problem this was. And people were accusing me of aggrandizement and exaggeration. When the virus was discovered, we learned some very, very sad things that were part of the ultimate tragic truths related to HIV. We of course had collected thousands of specimens. And now, thanks to the scientists who discovered the virus and discovered the way to test for the virus, we could go back to our specimens and find out what we could about the natural history. We could give some life to the iceberg. What we found in our transfusion-associated cases, where there had been one blood donor who had been immunocompromised many years before-- he still had no symptoms many years later when we interviewed him-- we found that the person was asymptomatic when he donated blood. And we found that they were often still asymptomatic many years later, but in virtually 100 percent of cases, they remained infected with the virus. That is, very soon we found out that a positive antibody test meant life-long infection, which was almost always progressive over time. A really horrible thing. We were fortunate to have cooperation from the gay community in San Francisco and the San Francisco Health Department for our studies of Hepatitis B. And during those studies, we collected 7,000 specimens from gay men in the late 1970s. What we learned was that by the time the first cases were reported in that group of 7,000 men, more than 40 percent were infected with HIV in retrospect. And by the time that there were 25 cases reported, there were 5,000 men reported with HIV. That the virus precedes the disease in a community as it does in an individual. When those first five men were reported with pneumocystis from Los Angeles, there were over 250,000 gay men in the U.S. already infected with HIV. Virtually all of those men have now died. By the time the virus was discovered, there were more than 500,000 people in the United States infected with it and millions worldwide. And this has been true in every country. By the time the cases appear, by the time people become sick, by the time the wards become filled with people who are sick, millions are infected with a virus that will last for life. And absent treatment will be universally fatal. When the epidemiologic pattern became very clear -- that is, the cases of pneumocystis and Kaposi's sarcoma and other infections that were occurring were recognized first in gay men and then in heterosexual injecting drug users, and then eventually, in some of their heterosexual partners, and then finally in persons with hemophilia, there was a need to draft recommendations for people to prevent the disease. Because of the specific case definition, the patterns of a transmissible agent were so clear that it was easy for CDC to draft recommendations for prevention and to get rather rapid consensus from other public health service agencies on what should be done. And the recommendations then were adopted by the World Health Organization, the AMA, physicians who cared for gay men, blood banks, the American Red Cross and others. The initial case definition of AIDS was tracking the end stage of a syndrome, and it was very specific for purposes of determining patterns. Of course, when the virus was isolated, that allowed for refinement of the AIDS-case definition to be certain that the people were infected with the virus. Well over 99 percent of cases were also positive for HIV when the tests were done. So the HIV test was added initially to the case definition. The definition was revised later in -- two more times, to add other serious and life-threatening HIV-related conditions to it. And then eventually it was revised to take into account severe immune suppression, which again, tracking the end stage of HIV disease. What has been remarkable with our understanding of HIV infection is that the patterns of transmission have remained quite stable over time. It is virtually never transmitted through casual contact, and is transmitted through sexual contact or exposure to blood, or perinatally from mother to either her newborn or through breastfeeding to her baby. When the first cases of AIDS were reported in 1981, the country was in was being disciplined by the Reagan administration toward fiscal austerity, particularly in the public health service and other domestic programs. The CDC and the NIH both were feeling quite poor. And there was essentially no direct funds for AIDS for most of that first year or two. When the scope of the problem became clear, then funding became available for AIDS: for prevention, for science, for research, and eventually for care. And that money was very important in mobilizing the public response and community response, both with health departments and with providers throughout the country. I think that the United States can be proud of many aspects of how we ve responded to AIDS. There was a rapid response in a fiscally difficult time by public health service scientists and investigators in working with people in the community to identify the problem and publicize it to the extent we could, when we were in an era of denial. And I think the initial prevention recommendations were extremely important in reducing transmission of the yet-to-be-discovered virus. We were instrumental in discovering the virus, and in developing the diagnostic tests and getting them on the market very, very, quickly to both protect the blood supply and to diagnose HIV infection, which, again, leads to further prevention. United States investigators supported by the NIH or at the NIH developed trials to test AZT as the first drug, and to test perinatal transmission prevention by giving AZT, again, to pregnant women, both during pregnancy, during delivery and to their newborns. United States investigators were very important in many of the other scientific discoveries, including the development of HAART and the ongoing research developments. The diagnostic testing has been revolutionized. Scientists from 20 years ago would have been amazed that we can measure viral loads, for example, with such accuracy. And they ve been very important in determining both abilities to prevent HIV as well as measuring the impact of treatment. The last two things I guess I would say are that U.S. scientists and investigators and the U.S. Federal Government has been instrumental in the global response. And this includes the elected officials who have sponsored our global programs, including PEPFAR, as well as the many doctors and nurses and administrators who have worked on the problem globally, and advocated for it. And then the last thing is that I think that the U.S. can be proud of the response of our advocates in the community. In my life I ve not seen a disease in which people who are infected with the virus themselves, despite suffering enormous stigma and illness, have been so important in the advocacy and partnership in dealing with the problem. And the country has, sometimes reluctantly, but often embraced them as part of the solution. And that was a lesson for all of us. There are many problems in the world which seem overwhelming. And HIV went from being a problem that was not recognized, a disease which had no cause, and then eventually when it had a cause, it had no treatment. And when it had a treatment, it was quite ineffective. It would seem to be difficult to stop transmission from a pregnant woman to a newborn. There s a lot of reasons to be skeptical. And of course, the world's problems often seem impossible to deal with. But they're only dealt with, really, one step at a time, by people who are motivated and committed. And who work together with each other, and who are willing to stand on the shoulders of the people before them. Fortunately, science and the community had dealt with problems before. The gay community had worked with scientists in Hepatitis B vaccine. Scientists had discovered how to measure the immune system, how to grow the types of viruses that cause this disease. And HIV has taught us that there are anti-viral treatments, which now can be used for hepatitis and for other infections. Our skepticism about our ability to make a difference has often been premature, because of the discoveries of others. After HAART became available, everyone said, It will never be used in the developing world. It's way too expensive. And there's still a long ways to go because of the size of the problem in many countries and the inadequacy of health care. But now, millions of people throughout the world During the first couple years of AIDS reporting, it became clear that the problem was occurring in Haiti, and from cases reported in Europe from immigrants from Central and West Africa, there seemed to be many more cases. Along with investigators from the National Institute of Health and the Institute of Tropical Medicine in Belgium, Dr. Joe McCormick and Sheila Mitchell from CDC first went to Kinshasa, in the country that was then called Zaire, to see the extent of the problem there. They were amazed by talking to doctors and seeing patients there that the condition was extremely common in Kinshasa, and warranted much further investigation. So we recruited Dr. Jonathan Mann, who was working in New Mexico at the time, to head up a project along with Dr. Skip Francis from NIH and colleagues from Belgium, and Dr. Bila Kapita, who was the chairman of medicine at Mama Yemo Hospital in Kinshasa, to begin a project in 1984 which was called Projet SIDA. Projet SIDA soon became the largest research project that CDC had ever conducted in Africa and the largest that anyone was conducting at the time in the African continent. Dr. Mann worked there for two years and then was recruited by the World Health Organization to begin the global program on AIDS at W.H.O. And during his life, both at W.H.O. and afterwards, he was the most well-respected advocate for seeing AIDS as a problem related to social justice. I began thinking about or working on this problem about 10 days before the first cases were reported in 1981. So I m still the director of Emory Center for AIDS Research, getting ready for grant renewal, a proposal. I m actively involved in projects in the community here in Atlanta, as well as in India and the continent of Africa and throughout the world. Our priorities at Emory Center for AIDS Research are to work on prevention from a number of different scales: prevention related to behavioral aspects of transmission, understanding behavior in discordant couples of gay men or discordant couples that are heterosexual; the intersection between testing, treatment, and behavior, because all of these things involve behavior; the development and testing of vaccines; and the development of curative therapy. So we have scientists at Emory who are engaged in what I think are many of the most important and crucial aspects of the problem. HIV infection is an infectious disease but it s also a chronic disease. And it s gone from what initially was epidemic-- that is, something which was occurring in greater frequency than expected and growing very rapidly, to something which is now part of our environment, unfortunately. It is the fourth leading cause of death in the world, the leading cause of death in the continent of Africa, leading cause of death among gay men in the world, and it s something which -- for which there is going to be no short-term solution. As with dealing with other chronic diseases, there s no room for burnout. And because the problem will not burn out. Those of us who have devoted much of our professional lives to this have to seek renewal, we have to make sure that we re not running on fumes, and we have to be committed to a problem which will outlast us. When I become skeptical, when I say, s going to be very difficult to develop a vaccine, I don t see how it s possible, or How can we ever cure HIV? I think back 20 years or 30 years when people said we would never find the cause of this disease, there would never be any drugs that could treat such a viral infection, we ll never be able to determine viral load, it s not going to be possible to stop a pregnant woman from transmitting it to her child. And so the skepticism that I feel is beaten down by the accomplishments of the past, and also the enormity of the problem. The biggest challenges that AIDS causes haven t really changed, although there s an appetite always for quick solutions and the newest findings. But the biggest challenges remain the same, from my point of view. We have a lifelong infection which is silent in most people until they become desperately ill many years later. And it s transmissible during a time when it s silent. So the problem is that throughout the world most of the people who are infected with the virus don t know it. Even in the U.S., 20 percent of people who are infected are unaware of their infection, and they re responsible for, perhaps, 50 percent of the transmissions or more. Throughout the world in developing countries, the people who don t know they re infected transmit the vast majority of infections. That is the central biggest problem from my point of view, this inapparent transmission and inapparent infection that exists in HIV epidemic. But in order to change that we have to have targeted approaches to testing, and we have to have ways to provide services and care for the people who are detected to be positive. I mean, can you imagine if breast cancer were transmissible, and we had a program to do mammograms for everybody, but we couldn t treat the cancer if we found it? Well, that s the similar problem we have with HIV. Or if somebody was a drug user, and they had breast cancer but you couldn t treat the drug use or the breast cancer, because they were related to each other. So the linkage between prevention and care is extremely important. Now biologically, of course, the biggest problem with HIV is that there s no vaccine and there s no cure. So if we had a preventive vaccine that could prevent infections from occurring, and this vaccine would last for a very long period of time, that would be a tool that could radically change the course of the epidemic if it were applied appropriately. Similarly, of course, curative therapy would be a real breakthrough, because it would reduce the number of transmitters as well as saving the lives of people. So these remain the biggest goals, I think, in prevention and care, and the enemies are the silent infection, discrimination, and scarcity of resources throughout the world. 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Channel: HIV gov
Views: 26,936
Rating: 4.5406699 out of 5
Keywords: James Curran Oral History, HIV, AIDS, AIDS.gov, 30 Years of AIDS, Emory University, HIV.gov, Dr. James Curran, History of AIDS, History of HIV
Id: a8Gwl4dHR3A
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Length: 35min 36sec (2136 seconds)
Published: Wed Jun 29 2011
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