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Our platelet donors are drawn primarily from volunteers from Montgomery County. They too, over the years, have tended to be repeat donors and have been screened in multiple ways. The demographics are a slightly different. These donors have a slightly higher male to female ratio. They have a lower percentage of ethnic minorities. I honestly do no know the educational level, but they obviously are not as medically oriented as the population here in this institution.
Harden: Did a higher percentage of them turn out to be HIV-positive?
Klein: No, in fact, we have, I believe, only one in that group, again probably reflecting the fact that they are screened in multiple ways over the years and are volunteers.
Harden: As I recall, you not only followed your donor pool longitudinally, but you must also have followed the health care providers here in the Clinical Center who had had needlesticks and so on. Were you doing the laboratory work on that?
Klein: We collaborated on that, but we were not the lead group. Dr. David Henderson, in the Epidemiology Service, started those studies. We were obviously very interested in those studies and did all of the testing for them, and some of the counseling for the individuals. Unfortunately we had the first health worker in the hospital, and one of the first health care workers in the United States, to become definitely infected by a laboratory accident in our department. Ironically, it was a health worker who was a meticulous person and who did all the right things. She was handling a tube of blood from a known infected individual and was double-gloved. She removed the cap from the tube of blood–it was a rubber vacuum tube–and when she removed the cap, the lip of the tube broke off and the glass that was broken cut through her glove and cut her finger. Of course, we knew immediately that she was at risk and tested her. She unfortunately seroconverted in about eight weeks and sadly went on to develop the disease. So we were very much aware that this was a possibility and very interested, obviously, in what the risk was to our staff. As it turns out, the risk is relatively low, but we did not know that in 1985.
Harden: Your staff was, I presume, dealing with all sorts of different situations such as you described with vials of blood from infected individuals and with taking donors coming in, although with your population of donors it probably did not seem to be as great a risk.
Klein: That is right. I think we were able at least to say to our donor screeners and bleeders, that the people they were dealing with were relatively safe. They were probably safer than someone you might meet at a club at night in downtown D.C. But the patients in the Clinical Center–NIH was studying AIDS patients–were obviously a risk to the health care workers who were handling their specimens.
Harden: I comment on this because we have a friend who was a laboratory technician in our health maintenance organization. Apparently the organization did not tell the laboratory technician which blood was infected and which was not for a while. She was very worried about it.
Klein: We always told our staff that all blood was potentially dangerous. We told them that because of the hepatitis experience. We said, “Any blood that you see coming through here, no matter what we test it for, can transmit hepatitis, so you have to be careful.” In fact, smoking in the laboratory, ever since I arrived here, and I am sure before that as well, was grounds for firing, certainly grounds for removal from the laboratory. Eating in the laboratory was absolutely forbidden for any reason. Storing food in a refrigerator in a laboratory where blood might be stored again merited just about the most severe penalty for these kinds of actions. We realized very early that our staff was at risk for hepatitis and, in fact, many of our staff were infected with hepatitis B because, as it turns out, that particular virus is much more infectious than HIV is. But the fact that if you were stuck with a hepatitis B positive needle, your chances of becoming infected were somewhere between 15 and 30 percent–and because we did not know what the risk was from the AIDS agent–made us incredibly cautious about that in the very early days. It turns out, fortunately, that HIV is much less infectious, but unfortunately, of course, we saw the results of an exposure in our laboratory.
Harden: Can you give me a percentage for HIV?
Klein: Yes. About 0.5 percent of known positive needlesticks seroconvert. About 0.5 percent, 5 per 1,000, compared to, say, somewhere between 15 and 30 per 100 with hepatitis B.
Harden: From the time that the virus was identified, you had a known agent to react. Would you describe what steps you took with regard to collecting blood, and what experiments you were involved with?
Klein: I think I told you in the first interview that we did go back to our frozen specimens and we did find two donors who were positive. We followed the specimens of the recipients of their blood and demonstrated that, in fact, those donors had infected the recipients. We defined the period of latency between the time a patient was transfused and the time the test became positive, and that was about six to eight weeks.
The second thing that we were able to define from those specimens, was we had some individuals–donors–whose specimens tested positive by the ELISA test but did not test positive by the additional test, the Western blot. In fact the recipients of their blood did not become infected. That, again, was immediate, very reassuring information that these were false positives and that we were not seeing more real infections than we had thought. Those studies were very important.
I told you about the studies with the chimpanzees that were very important for a couple of reasons. They demonstrated, first of all, that blood transmitted the virus unequivocally to another primate, and they established the fact that the chimpanzee was a model for research.
After the advent of the HIV test another extremely important study that we jumped right in to was we said, “We would like to know the natural history, or what happens, with these donors who are positive.” All of the data that had been collected previously was from individuals, gay males, who had been picked up either because they had become sick, or because they were in a cohort of gay males that was being studied. No one had really prospectively followed healthy blood donors before.
So we called up the Regional Red Cross and we said, “We would like you to send up any true positives that you have, and we will repeat the testing if you do not want to do additional testing. As controls we would also like to follow some of these people we think are false-positives, some of the ELISA repeat reactives that are Western blot negatives. We want to know whether these people go on to get the disease.” The Red Cross agreed to do that. As I said, we had very few in our NIH donor population, but the Red Cross had hundreds. They asked everyone who was positive whether they would be willing to participate in the NIH study. By participating in the NIH study they would come to NIH, be retested, have a battery of other tests, have a complete history and physical examination done by a physician, and they would be followed every six months. They would not be treated with anything because there was not anything to treat them with. About all the benefit they would get out of this was that they would receive the information that was available as soon as there was information available, because at that time the federal government was really on the cutting edge of everything, and people looked to NIH for information. About half of all the positives agreed to do it. The other half did not want to do it.
Harden: Was this the Washington D.C. Red Cross?
Klein: The D.C. Red Cross. There were about 170 people who were true positives, and we got another 60 or so who were false-positives. We could have gotten many more of them, but that was a sufficient number for the study, and this was a major undertaking for us.
We did something that was a first-time-ever at NIH, I believe, which was novel and difficult, and that is, we established a totally separate numbering system for these individuals outside of their hospital records so that no one could retrieve the results. I am sure that you recall the hysteria involved with identifying a person who was positive for the AIDS test, and there were federal regulations about releasing the identity or invading the privacy of an individual. We were able to set up a system where subjects were followed at NIH, but were followed with a completely different numbering system. They did not have a hospital number, and could not have their information retrieved by anyone but a small, select set of investigators. Going through the IRBs (Institutional Review Boards) and the ethics committees, this was very difficult to do. There were many arguments about how this should be set up and whether it should be set up, but it was, and it remains until this day.
Those true positives and false-positives have been followed now since March of 1985. This is the largest series. The individuals were seen every six months. Specimens of serum, cells, and nucleic acid were frozen away, so that should additional testing be useful for the effort against AIDS, we would have those specimens over time in an interesting cohort of individuals. It has been a very helpful study from a variety of standpoints. First of all, it did define the fact that people who were false-positive by this assay did not get sick; that their immunologic status did not change; that they remained entirely normal. You could only say that after following a group for about five years. Prior to that you could guess. From our refrigerated and frozen specimens you had a pretty good idea. But this was the first prospectively followed cohort, so they did not get sick. The true positives, of course, did, and about 16 percent per year developed frank AIDS.
The other aspect that was important was looking at the demographics of the people who came into the study, again realizing that this was not a randomized group but a self-selected group. We did not know what made one person say, “I am never going to call them at NIH.” But what we found out was that a high percentage were African Americans. This does not seem surprising in 1993, but in 1985 there were people who were saying that black Americans did not become infected this was a white, gay male disease.
Harden: You are certainly aware of the Tuskeegee syphilis experiment?
Harden: There is a group at the University of Maryland which published a paper in the American Journal of Public Health in 1992 saying that part of the reason African Americans may have said that they did not do this was a left over fear of being in federal government studies. Apparently there was even an impression that the federal government has given the men at Tuskeegee syphilis. Did you hear anything like this, or about this?
Klein: Not from our group of individuals. At the time, of course, we had to talk to all of our donors about the rumors going around that HIV was a virus developed by the CIA. One rumor was that it was developed up in Frederick, that it had gone to Africa first via the CIA, second via vaccines that had been used for polio testing in Third World countries. We did hear all of these rumors, but none of the people that came to see us really believed any of those things. A high percentage turned out to be gay males and they were black gay males. But at the time–it seems foolish today–people felt that if you were black you were somehow protected. That was actually being said. While we had never believed that, here were data to look at. Now, our sample was clearly biased in that it came from Washington, D.C., where a high percentage of blood donors was likely to be African American. If you were young, black, and certainly if you were a gay male, you were at risk in our sample.
We had an opportunity to follow these people over time and see what happened to them in terms of their immune status, in terms of developing frank AIDS, and, unfortunately, in terms of dying. What we found, as you might guess, is that about 12 percent per year of those who developed AIDS died.
As we continue this study now, of course, these individuals have been offered AZT or ddI, and they have been offered participation in other NIH therapeutic studies when those have become available. There has been some benefit to these individuals whom we have followed over the years and have been so helpful to us.
We found out a lot about their sexual practices. One of the things that was very unfortunate, and again seems hard to understand in 1993, was that when we started our studies we desperately wanted a psychiatric component to the study and were unable to get one. We wanted psychiatrists involved for two reasons. We wanted to find out something about why these individuals had donated blood, since they were being screened with questions and so on and still had donated. We also wanted to have that as a resource, realizing that a positive test result is a tremendous psychological blow for someone. We could not find a group within the federal government that was interested in following these individuals. We tried people at NIH, and the Department of Defense, and we simply could not find anyone who was willing to devote the resources in 1985 to a brand new cohort of individuals about to be told that they had AIDS, or a virus that frequently resulted in AIDS, and that they were going to be followed prospectively along with controls. To this day I feel that this as one of the great lost opportunities to find out about peoples’ attitudes, how they were affected initially and how they changed over time.
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