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What is with...
All the posts about "rare strains?" How (medically) possible is it to have a strain undetectable by modern ELISA, rapid and PCR testing?
Western Blot Test for unknown HIV strains
Rick Sowadsky, MSPH
Senior Communicable Disease Specialist
Nevada State Health Division
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Questions:
Hi. As I understand it, Western Blot looks for specific HIV proteins like p24, p17, etc. So, wouldn't WB be a good test for detecting rare/unknown strains? I noticed that for the African lady who has a group O infection, her WB was indeterminate, while the Elisa tests were negative. Therefore, shouldn't both the WB and Elisa tests be performed to cover the case of rare/yet undiscovered strains, especially in the blood supply?
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Mr. Sowadsky's Response
Hi. Thank you for your question.
The antibody tests (ELISA, Western Blot, and IFA) are NOT designed to pick up different strains of HIV. They are designed to pick up various proteins found in most/all strains of HIV. The Group "O" strain is the rare exception. This extremely rare strain will sometimes not show up on conventional tests. However tests are now being modified to pick up even this rare strain. There are only about 100 people worldwide who have been found to have this unusual strain. Most of those people were found in Central and Western Africa. Because of the high risk for HIV and other bloodborne diseases in this part of the world, people who have lived in these areas (or had sex/needle sharing contacts with persons from Sub-Saharan Africa) would not be permitted to donate blood.
Western Blots are usually only done if the ELISA tests are repeatedly negative. In the case of the African woman living in Los Angeles, sometimes her ELISA tests were negative, but most of the time they were positive. When they did the Western Blot on her, this was done after a positive ELISA test. The Western Blot in this instance came back indeterminate (neither positive nor negative).
When we're dealing with screening for HIV, it would be extremely unusual for the standard antibody tests not to pick up an infection 6 months after a possible exposure to the virus (regardless of the strain). Doing Western Blot tests on every sample will not pick up rare or unusual strains any better than an ELISA test. In keeping the blood supply safe, we go beyond screening for HIV. In the USA, anybody whose even been at risk for HIV would not be allowed to donate. Because this woman was from Sub-Saharan Africa, she would never have qualified to donate blood.
When a person gets an antibody test, the first test that's usually done is the ELISA Test. The ELISA test is very good at giving a positive result in a person who is truly positive, but sometimes, it will give a false positive reading. Therefore, any time the ELISA is repeatedly positive, it has to be confirmed with a second, different test. The Western Blot is the most common confirmatory test (the IFA test is another confirmatory test). The confirmatory tests are very good at giving a person a negative result when they're truly negative. Therefore these confirmatory tests are good at ruling out false positives on an ELISA test.
So in summary, Western Blot tests will not pick up rare strains of HIV any better than the ELISA test. And in the case you referred to, most of her ELISA tests did come out reactive (including the test where they did the Western Blot). The antibody tests are not strain specific. They're designed to pick up most/all strains of HIV. The extremely rare Group "O" strain of HIV will usually show up on these tests, but not always. When it comes to blood donations, persons at risk for Group "O," or at ANY risk for HIV, would not be allowed to donate. And ALL blood donated in the USA is screened for HIV-1 and HIV-2, using the p-24 antigen test, the ELISA test, and when the ELISA test is repeatedly positive, the Western Blot test as well
Rick Sowadsky, MSPH
Senior Communicable Disease Specialist
Nevada State Health Division
--------------------------------------------------------------------------------
Questions:
Hi. As I understand it, Western Blot looks for specific HIV proteins like p24, p17, etc. So, wouldn't WB be a good test for detecting rare/unknown strains? I noticed that for the African lady who has a group O infection, her WB was indeterminate, while the Elisa tests were negative. Therefore, shouldn't both the WB and Elisa tests be performed to cover the case of rare/yet undiscovered strains, especially in the blood supply?
--------------------------------------------------------------------------------
Mr. Sowadsky's Response
Hi. Thank you for your question.
The antibody tests (ELISA, Western Blot, and IFA) are NOT designed to pick up different strains of HIV. They are designed to pick up various proteins found in most/all strains of HIV. The Group "O" strain is the rare exception. This extremely rare strain will sometimes not show up on conventional tests. However tests are now being modified to pick up even this rare strain. There are only about 100 people worldwide who have been found to have this unusual strain. Most of those people were found in Central and Western Africa. Because of the high risk for HIV and other bloodborne diseases in this part of the world, people who have lived in these areas (or had sex/needle sharing contacts with persons from Sub-Saharan Africa) would not be permitted to donate blood.
Western Blots are usually only done if the ELISA tests are repeatedly negative. In the case of the African woman living in Los Angeles, sometimes her ELISA tests were negative, but most of the time they were positive. When they did the Western Blot on her, this was done after a positive ELISA test. The Western Blot in this instance came back indeterminate (neither positive nor negative).
When we're dealing with screening for HIV, it would be extremely unusual for the standard antibody tests not to pick up an infection 6 months after a possible exposure to the virus (regardless of the strain). Doing Western Blot tests on every sample will not pick up rare or unusual strains any better than an ELISA test. In keeping the blood supply safe, we go beyond screening for HIV. In the USA, anybody whose even been at risk for HIV would not be allowed to donate. Because this woman was from Sub-Saharan Africa, she would never have qualified to donate blood.
When a person gets an antibody test, the first test that's usually done is the ELISA Test. The ELISA test is very good at giving a positive result in a person who is truly positive, but sometimes, it will give a false positive reading. Therefore, any time the ELISA is repeatedly positive, it has to be confirmed with a second, different test. The Western Blot is the most common confirmatory test (the IFA test is another confirmatory test). The confirmatory tests are very good at giving a person a negative result when they're truly negative. Therefore these confirmatory tests are good at ruling out false positives on an ELISA test.
So in summary, Western Blot tests will not pick up rare strains of HIV any better than the ELISA test. And in the case you referred to, most of her ELISA tests did come out reactive (including the test where they did the Western Blot). The antibody tests are not strain specific. They're designed to pick up most/all strains of HIV. The extremely rare Group "O" strain of HIV will usually show up on these tests, but not always. When it comes to blood donations, persons at risk for Group "O," or at ANY risk for HIV, would not be allowed to donate. And ALL blood donated in the USA is screened for HIV-1 and HIV-2, using the p-24 antigen test, the ELISA test, and when the ELISA test is repeatedly positive, the Western Blot test as well
You are mistaken a bit about your assessment of HIV mutations. HIV Ab tests test for proteins specific to HIV, however, there would have to be a major mutation, like very major, for the test to not pick it up at all. I posted this to Chris a few weeks ago, maybe it will provide some insight for you.
"I asked this question to my infectious disease lecturer and he said that although HIV mutates a lot, the tests today cover all strains because they test for antigens (basically HIV proteins that the body reacts to with antibodies) that are COMMON to all strains. The mutations usually are in smaller parts of the HIV virus that are not tested for anyway. I don't know if you have taken an evolution course, but in Darwinian evolution (the accepted mechanism of change in the biologic community), proteins that are vital to any cell or organisms (or virus!) survival are highly conserved, meaning that they do not change. They remain the same between species and over billions of generations. The point is, why would something change if it was so highly important and vital to the cells/organisms survival the way it was? The same is true for HIV. The proteins tested for on the ELISA/Western Blot are highly conserved proteins, common to all strains of HIV. HIV mutating these proteins would most likely be detrimental to the virus, hence the reason they are highly conserved. HIV has many, many, many other proteins that it uses, and they mutate frequently, but do not and will not affect the test result. Even if one of the big proteins that they tested for mutated, you would have tested positive based on the conserved proteins.
Another thing to consider about mutations is that the western blot and ELISA are based on antibodies. Antibodies are proteins in the host that respond to foreign proteins in an invader, such as HIV. I know you know this, but I say this just to illustrate my upcoming point. Antibodies bind to protein sequences, meaning it could be any number of amino acids either in sequence or in different parts of the protein that happen to touch when the protein folds. It is highly unlikely that HIV would mutate to such an extent that the antibodies on ELISAs and western blots would not respond to it. The odds of it mutating so much in one generation so as to completely change the whole amino acid sequence are infinitesimally small, especially in only a few generations. Any mutation that changed the proteins that are tested (which again, based on evolution, is unlikely) would at least be partially reactive with the antibodies used to test, which would not give you your consistently negative test results. You are right to think/say that even a new strain would be weakly reactive. In fact, it is likely that it would be indistinguishable from a positive test from one of the normal strains. ""
"I asked this question to my infectious disease lecturer and he said that although HIV mutates a lot, the tests today cover all strains because they test for antigens (basically HIV proteins that the body reacts to with antibodies) that are COMMON to all strains. The mutations usually are in smaller parts of the HIV virus that are not tested for anyway. I don't know if you have taken an evolution course, but in Darwinian evolution (the accepted mechanism of change in the biologic community), proteins that are vital to any cell or organisms (or virus!) survival are highly conserved, meaning that they do not change. They remain the same between species and over billions of generations. The point is, why would something change if it was so highly important and vital to the cells/organisms survival the way it was? The same is true for HIV. The proteins tested for on the ELISA/Western Blot are highly conserved proteins, common to all strains of HIV. HIV mutating these proteins would most likely be detrimental to the virus, hence the reason they are highly conserved. HIV has many, many, many other proteins that it uses, and they mutate frequently, but do not and will not affect the test result. Even if one of the big proteins that they tested for mutated, you would have tested positive based on the conserved proteins.
Another thing to consider about mutations is that the western blot and ELISA are based on antibodies. Antibodies are proteins in the host that respond to foreign proteins in an invader, such as HIV. I know you know this, but I say this just to illustrate my upcoming point. Antibodies bind to protein sequences, meaning it could be any number of amino acids either in sequence or in different parts of the protein that happen to touch when the protein folds. It is highly unlikely that HIV would mutate to such an extent that the antibodies on ELISAs and western blots would not respond to it. The odds of it mutating so much in one generation so as to completely change the whole amino acid sequence are infinitesimally small, especially in only a few generations. Any mutation that changed the proteins that are tested (which again, based on evolution, is unlikely) would at least be partially reactive with the antibodies used to test, which would not give you your consistently negative test results. You are right to think/say that even a new strain would be weakly reactive. In fact, it is likely that it would be indistinguishable from a positive test from one of the normal strains. ""
Not necessarily. As in Any Test, You Have to Know what to Look For in the First Place.
Hence Different Assays for Viral load HIV-1 and HIV-2. Apparently It's not easy to Get Viral load tests for HIV-2 as it is for 1. Tests have to be programmed to Know what to look for. I'm Guessing PCR is More Accurate as mutation would have to affect more than the antigenic sites, so it would become a totally different animal. Reverse transcriptase is an enzyme, that would be positive anyway. You'd have to speak to a Immunologist
Hence Different Assays for Viral load HIV-1 and HIV-2. Apparently It's not easy to Get Viral load tests for HIV-2 as it is for 1. Tests have to be programmed to Know what to look for. I'm Guessing PCR is More Accurate as mutation would have to affect more than the antigenic sites, so it would become a totally different animal. Reverse transcriptase is an enzyme, that would be positive anyway. You'd have to speak to a Immunologist
all the talk about "rare strains" is coming from those who do not accept the fact that they were not at risk and do not have HIV.
Point : = Modern Tests 99% Accurate for 99% Strains.
If they werent, How would you know you Had HIV. There would be a Huge Epidemic!
Were talking EXTREMELY RARE cases.
Just saying, even in these cases, HIV Can be Detected by Other Methods if there was a Known Exposure and Obvious clinical Symptoms and Other things ruled out.
There are usually other clues. It's been Gone over a LOT Here!
If they werent, How would you know you Had HIV. There would be a Huge Epidemic!
Were talking EXTREMELY RARE cases.
Just saying, even in these cases, HIV Can be Detected by Other Methods if there was a Known Exposure and Obvious clinical Symptoms and Other things ruled out.
There are usually other clues. It's been Gone over a LOT Here!
Really didn't understand your post Isaac, sorry. I'd assume that HIV antibody tests would pick up HIV antibodies regardless if you're not within the window period.
Antibody test are VERY Specific for Antigens. If that Antigen is Different Via Mutation. They Therefore are Not Detected. However, Using P24/DNA PCR Can usually Find Some Infections Antibody tests don't. CD4/CD8 ratio's and other indicators Could suggest HIV, but Not Conclusive. Extremely Sensitive tests Not Available Can detect reverse transcriptase enzymes.. I'm sure Manufactures do their best to update their tests. However, Even rare strains would be picked up. It would be EXTREMELY Rare for Mutant to Be so Different I Concuded. DNA PCR would detect genes Common to Different Strains. It would Have to Be HIV-3 But they would Know about it By Now.
Problem is Most exposures, we never find out if they actually were exposures.
Problem is Most exposures, we never find out if they actually were exposures.
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