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With the first HIV test in 1985, doctors thought they had discovered an absolute oracle: Will the patient live or die? Celia Farber reports on a recent, controversial paper that says the so-called AIDS test is too flawed to be reliable.
Whether or not people ought to submit to taking an "AIDS test" has long been the subject of furious debate. The impact of the life or lives of the people who do take the test, if it comes back positive, is incalculable, since HIV is still largely associated with surefire death.
The debate about the HIV antibody test has been long, complex and anguished. No single diagnostic test in the history of modern medicine has had such a momentous impact on the lives of the individuals who rely on it. Since the beginning of the AIDS crisis, people have had very dramatic responses to the test, lapsing into severe chronic depression and anxiety, quitting, or losing their jobs, taking very toxic medications such as AZT and ddI, getting divorced, having abortions, taking their lives and sometimes even other people's lives, all based, not on diagnosis of AIDS, but merely a positive antibody test.
Given that the test holds such power, its flaws and shortcomings are extremely significant. Unfortunately, it is only now that this immensely important subject is being investigated.
An Australian research team has published a review article in the June 11 issue of Bio/Technology (E. Papadopoulos-Eleopulos, V. Turner & J. Papadimitriou, 1993, "Is a Positive Western Blot Proof of HIV Infection?", Vol. 11, pp 696-707) that calls into question the accuracy of even the most accurate of the HIV antibody tests, the so-called Western Blot test, which is said to be over 98% accurate. They state that the test is seriously flawed on several counts: that it is not standardized, that it cross reacts with non-HIV proteins, and that ultimately, it is not reliable proof of actual infection with HIV.
Through their sharp critique of the methods of testing for HIV, the authors raise astonishing points about the virus itself – what is known and not known, what is seen vs. what is assumed. In the end, we get a dazzling insight into the precarious and fickle world of retrovirology. How infinitely complex it is, compared to the simple terms in which we've come to think of it.
The article, entitled "Is a Positive Western Blot Proof of HIV Infection?" was published in the June 11 issue of Bio/Technology a science journal put out by Nature Publishing. The Australian researchers, Eleni Papadopoulous-Eleopulos, Valendar F. Turner and John M. Papadimitriou, conclude that "... the use of antibody tests as a diagnostic and epidemiological tool for HIV needs to be reappraised". "A positive HIV status has such profound implications", they write, "that no one should be required to bear this burden without solid guarantees of the verity of the test and its interpretation".
Eleopulos and colleagues examine both HIV antibody tests: the enzyme-linked immunosorbent assay (ELISA) test, the first test used to screen blood, which costs about $50, and the Western Blot (WB) which is used to confirm a positive result on the ELISA, and costs closer to $100. They sum up the problems with both tests by making four major points: The tests are 1) not standardized, meaning that different labs have different criteria for specifying what is negative and what is positive; 2) not reproducible, meaning the test fails when tested against itself, and repeated tests can be alternately positive and negative; 3) proteins that are thought to be exclusive to HIV may instead be cellular contaminants, or debris; and 4) there is no "gold standard", for the HIV test. Every diagnostic test must have a "gold standard", and in this case it would be HIV itself, but the authors argue, this is impossible since HIV has never been isolated in pure form without cellular contamination. Even the Polymerase Chain Reaction (PCR), the one test that looks for HIV genetic material as opposed to viral antibodies, detects only one viral gene, the researchers argue, not the virus in its entirety. The PCR is far more sensitive than the WB. It costs several hundred dollars and is not commonly used.
The first test developed for HIV in 1985, the ELISA test, was developed to screen out HIV from the blood supply. It is highly sensitive, and very nonspecific, which means it gives a positive result easily even when there is no HIV present. As many as four out of five ELISA tests cannot be confirmed by Western Blot.
The ELISA is still the only test that is used in the Third World, most notably Africa, where very alarmist projections about HIV in the population have been made. In the United States, no person is supposed to receive a result that is based only on ELISA, a test which is used primarily as a first filter for the blood supply. Instead, a positive test is given when a person has one or two positive ELISA tests, which are them confirmed by a single WB test. However, the Bio/Technology article details many cases of the test being inaccurate despite all these steps being taken. Often, a second WB contradicts the first one. For example, they cite data from a mass testing done by the U.S. Military which contained some startling findings. There were 4000 people who had two positive ELISAs followed by a negative WB (note: all of those 4000 would be called HIV positive in Africa and HIV negative in the West). But perhaps more startlingly, there were 80 cases of people who had two positive ELISAs and a positive Western Blot, followed by a negative followup Western Blot. In other words, those 80 people, had they not been a part of this particular, scrupulous study, would have been told they were HIV positive, since a single positive WB is all that is required, but in fact they were negative. How many other people who have been told, based on a single positive WB that they are positive, are really negative?
Though it is not necessary to perform a test in order to diagnose AIDS, a positive test does confirm, according to Centers for Disease Control (CDC) regulations, an AIDS diagnosis. In the absence of a positive HIV test, conditions get treated for what they are; with a positive result, they all get labeled AIDS. The definition of AIDS includes some 25-30 different symptoms that occur in the presence of a positive HIV antibody test. What few people are aware of, however, is that the test is not an absolute, and there is a broad gray area that many people may fall into. For instance, many people fall into a never-mentioned category technically called WBI, or Western Blot Indeterminate, which means they hover between a positive and a negative result, and whether they are told they are positive or negative may depend on which lab tests their blood.
In both tests, ELISA and Western Blot, a patient's blood is added to an antigen preparation and supposedly, if HIV antibodies are present, they will react with the HIV proteins. But the Bio/Technology paper raises some disturbing points about the difficulty of developing a truly accurate diagnostic test, particularly when the microbe in question, HIV, is barely present in the blood.
HIV has been notoriously difficult to isolate, which is defined by Eleopulos as "separating the virus from everything else". Consequently, The Western Blot detects patterns of proteins thought to be specific to HIV. These are specified as 'p' for protein, followed by a number which represents a molecular weight. HIV is recognized by proteins p24, p17, gp41, gpl20, etc. These proteins have been said to be exclusive to HIV, but Eleopulos and colleagues demonstrate that they are not. One protein in particular, p24, is "currently believed to be synonymous with HIV isolation and viremia". But Eleopulos and colleagues detected p24 antibodies in a number of people who do not have HIV, including 13% of healthy patients with generalized warts, one out of every 150 healthy people with no afflictions, and 41% of patients with multiple sclerosis, among others. Conversely, p24 is not found in all HIV or even AIDS patients, they point out.
A major problem with the Western Blot that has never been assessed before is the fact that it cross reacts with other microbes. People who have certain autoimmune disorders, lupus and rheumatoid arthritis for instance, have been known to test positive for HIV even though they are not infected. The Bio/Technology paper demonstrates how the test can cross react with other microbes, including ones as common as malaria and TB.
Eleopulos, Turner and Papadimitriou report on a paper that examined a tribe of Amazonian Indians who have no contact with anybody outside their tribe and who have no incidence of AIDS, yet, 3.3-13.3% were HIV positive by Western Blot. "The above data", the authors speculated, "means either that HIV is not causing AIDS" ... "or" ... "the HIV antibody tests are nonspecific".
The study also details the fact that people with severely depressed immune systems, hemophiliacs and blood transfusion recipients for example, may test positive because they have so many foreign proteins and antigens in their blood. Receiving foreign cells or proteins from another person has been shown to cause immume disruption regardless of whether or not HIV is present.
The Bio/Technology paper specifies the vastly different criteria used by different institutions to interpret the WB test, and points out that an antibody test can only be meaningful when it is standardized, that is, "when a given test result had the same meaning in all patients, in al1 laboratories, in all countries". They sent one blood sample to 19 different laboratories, which all showed it to be HIV positive, but with wildly different band patterns. (With WB, individual proteins are recognized visually as colored bands). In another instance, a blood sample was sent 89 times to three laboratories; one pattern was reported 64 times, another pattern 19 times, yet another pattern 4 times, and once the sample tested negative.
The Food and Drug Administration (FDA) has the most stringent criteria for the WB interpretation, followed by the American Red Cross, and the Consortium for Retrovirus Serology Standardization (CRSS). According to the Bio/Technology paper, less than 50% of all AIDS patients have a positive WB when the FDA criteria are used. If the criteria of the CRSS are used, the percentage of positives goes up to 79%.
I asked a few scientists to comment on the Eleopulos paper, all of them signatories in the Group for the Scientific Reappraisal of the HIV Hypothesis. Dr. Charles Thomas, a former Harvard biologist, and founder of the Group for the Scientific Reappraisal of the HIV Hypothesis, said he thought the Eleopolus paper was "absolutely stupendous". "I think the HIV test has now been substantially challenged, and should be withdrawn from the market until these questions are resolved", he said.
Dr. Robert Root-Bernstein, a critic of AIDS scientific literature and author of Rethinking AIDS (FreePress) was more reserved. "I agree to a point – just because you have a positive WB doesn't mean you have HIV. But that doesn't mean you can throw out the whole thing either. What I'm seeing when I read the literature is that almost everybody who has antibody by WB has a positive PCR or co-culture if they go on to take those tests. And those are the papers that are ignored in here. This is a point on which I disagree with Peter Duesberg [who says that antibodies mean the infection is defeated]. I'm more than willing to admit that there are people who don't have virus but they have the antibody, and theoretically that could be a lot of people, but if you look at the studies that have been done, it appears that almost everybody who has the antibody actually is infected and does have a low level infection. I think that a positive HIV test is still a strong predictor for getting AIDS".
Root-Bernstein, in his book, has put forth that AIDS is a multifactorial syndrome, or possibly an autoimmune disease. "To be real convincing", he continues, "Eleopulos and colleagues would have to come up with a more accurate marker for AIDS. I'm still an agnostic about whether or not HIV is the cause, but it certainly is a good marker for it".
Dr. Peter Duesberg counters, "If a virus is to be claimed for a disease you want to see the virus, not an antibody against the virus. An antibody is not a virus and it's not a predictor for disease, it is only an indication that the virus has been neutralized, in some cases a long time ago. If you try to diagnose polio, hepatitis, measles you can find the virus, you don't have to mess around with antibodies. Only in AIDS do we focus on the antibody". Professor Alfred Hassig, who was head of the Swiss Red Cross Blood Transfusion Service for thirty-seven years, commented. "I think she [Eleopulos] is perfectly right. Every test in serology, immunology has false positives and false negatives. But Western Blot had been taken as a holy measure, and that is very unfortunate for the person getting the result". Root-Bernstein feels differently. "By the time you've got symptoms, does it really matter whether you've got HIV or not? You still have to be treated for AIDS. The big issue there is what we think is causing AIDS. I tell people to go see Dr. Joe Sonnabend [a New York AIDS physician]; he won't treat the HIV, he'll treat everything else. I think that's perfectly reasonable."
"The other thing is, I've got a file that keeps growing, that there are people who are positive by ELISA, Western Blot and PCR, who have low T cell counts, and they lose all those things. They seroconvert to HIV negative by all tests, and their T cells stabilize or go up. They're usually people who alter their lifestyle. It's important to point out is that even if you are positive that dosen't mean you will get AIDS. At least in a small percentage of cases, people can spontaneously eliminate an HIV infection". The suggestion that people "change their lifestyles", is one of the most inflammatory, frowned upon ideas in the AIDS debate. I asked Root-Bernstein to be specific.
"All the cases I've read are in one of two groups. Either limited exposure, like a girlfriend of a hemophiliac who leaves him or they start practicing safe sex, or they're gay men or IV drug users who quit. Quit the drugs or for gay men find a stable sexual partner and practice safe sex. As I said in my book, I don't think there's anybody who gets AIDS from a single exposure to HIV. Even if you look at the transfusion cases, most of those people got 20 units of blood. Most people are constantly reinfected".
"I think she [Eleopulos] makes some very excellent, important points", says Dr. Peter Duesberg of UC Berkeley, famous for his views that HIV doesn't cause AIDS. "She is correct to say that it is not chemically pure, that it is contaminated with human cellular proteins, and who knows what effect that has on the test result".
Duesberg, unlike Root-Bernstein, can see no value in the HIV antibody test, accurate or not. "With all other viruses the antibody tests, if they are done at all, are only there to show that you are immunized, you don't need another shot", says Duesberg.
When asked what the response in the scientific community to the Bio/Technology paper has been, Harvey Bialy, the editor of the study and scientific editor of Bio/Technology, said, "essentially none. I expected letters denouncing it, but I haven't received a single one". "None of the testing companies have withdrawn their advertising", Bialy said with a laugh.
"It sort of makes no difference what the truth is because the antigen test for the p24 antigen has been thoroughly discredited and is still used". "In this field [AIDS] what the facts are is irrelevant", says Bialy. "All people will say is that by pointing out that the antibody test may not be accurate you're encouraging people not to use condoms. No matter what you say which legitimately criticizes the science of AIDS, the accusation is always that you're encouraging people not to use condoms". I called Australia to speak to the research team, but they had been besieged by interview requests, though interestingly, not a single one from the American media.
The debate about this paper will probably be protracted. Some will denounce it as nonsense, others will follow its leads. But it certainly ought to have a sobering effect on HIV testing and the hysteria that goes with it. "Why does this paper matter?" Root-Bernstein asks rhetorically, "It matters to all the people who test positive for HIV by Western Blot and assume they have AIDS and are going to die, or that they have to take AZT. She [Eleopulos] has convinced me that the tests are not as good as most people think they are".