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False Negative HIV ELISA test

3rd generation ELISAThere are such things as False Negative HIV ELISA tests but they are very rare.

I have been pondering whether or not to write this article for a long time.

I finally decided to do it in the name of scientific truth and complete transparency.

What I do not want to happen is for this article to feed the unreasonable fear and paranoia that is already out there.

I want to state categorically that I still believe the HIV Combo test is 100% conclusive at 28 days post exposure and the HIV 3rd Gen ELISA Antibody test is 100% conclusive at 3 months post exposure.

Click here for more info on the HIV testing Window Period.

Note that the cases mentioned in this article are extremely rare, literally 1 in a million.

With all that in mind, let’s get into the topic proper.

Introduction

In the 1980’s when HIV was first discovered, we needed a way to determine if a patient was infected with HIV or not.

Out of this need was born the first generation ELISA test which tested for the presence of HIV specific antibodies in the blood. Over the years, these ELISA tests became more and more accurate. However, they all depended on one thing: the assumption that a patient who is infected with HIV will develop antibodies to HIV so that it can be detected in the first place.

Click here for more info on the Different Generations of ELISA tests

It was soon discovered that this was not always a valid assumption. There were instances where a person was infected with HIV but yet the ELISA test showed that he was not. This so called ‘False Negative’ ELISA test was initially blamed on the HIV Testing Window Period – the time from when a person is infected with HIV to when antibodies to HIV become detectable in the blood. However, we soon discovered that there were other, albeit extremely rare, causes of a False Negative HIV ELISA test.

Causes: 1. Window period  2. Non-Clade B Hypogammaglbulinaemia  3. End Stage AIDS  4. Hep C co-infection 5. Unkown (Sero-Negative HIV Infection)

The commonest cause of a False Negative ELISA – the testing Window Period

Initially, all cases of false positive ELISA tests were blamed on the testing window period. Till today, testing within the window period is still the commonest cause of a false positive ELISA.

The newer generation ELISAs can detect IgM antibodies which are produced much earlier than the IgG antibodies detected by older generation ELISA tests. This has significantly brought down the window period but it still hovers between 6 weeks to 3 months.

Click here for more info on the HIV testing Window Period.

Newer tests including the P24 and RNA PCR has made the testing Window Period even shorter. Furthermore, these 2 tests are not dependent on the presence of antibodies and therefore will still be positive in people infected with HIV but do not develop antibodies (sero-negative infections).

Click here for more info on the HIV Combo test
Click here for more info on the HIV PCR test

Non-Clade B HIV virus

Once the issue with the testing window period was worked out, another problem arose.

As most tests were developed in North America and Europe, most of the focus was on detecting Clade B viruses which were the most commonly found subtype in these areas.

As such, some HIV ELISA tests that were developed were not so sensitive in detecting non-Clade B viruses.

This problem was quickly picked up and nowadays, HIV tests are all designed to detect non-Clade B viruses.

Hypogammaglobulinaemia, Agammaglobulinaemia

This is an extremely rare cause of sero-negative HIV infection (i.e. infected with HIV but with no detectable antibodies in the blood).

Hypogammaglobulinaemia in itself is a very rare condition in which patients have a (frequently genetically induced) inability to develop antibodies. It is rarer still to find such a patient and infected with HIV.

To date, I know of only 1 reported case in the NEJM in 2005.

Sero-reversion in End-Stage AIDS

We all know that HIV destroys the immune system and eventually leads to AIDS.

At the very late stages of AIDS, the patient’s immune system may be so poor that he/she is unable to produce antibodies anymore.

The antibodies that were present in the blood then disappear. This is what we call sero-reversion (the disappearance of antibodies) as opposed to sero-conversion (the appearance of antibodies).

Patients in these situations are always extremely ill and the diagnosis of a HIV infection is made by RNA PCR viral load test.

Click here for more info on the HIV PCR test

Interestingly enough, when some of these patients are given HAART, their immune system comes back to life and they start producing antibodies again, leading to sero-conversion and positive ELISA tests.

Sero-reversion with HAART

Many people also ask about and are worried about sero-reversion with HAART.

This is extremely rare. There are 2 known case reports of such a phenomenon. This refers to months on HAART and should not be confused with PEP. So far, there have been no case reports of delayed sero-conversion or sero-reversion with PEP.

HIV and Hepatitis C Co-Infection

Co-infection with Hepatitis C can prolong the HIV testing window period up to 12 months.

Click here for more info on the effect of Hep C co-infection on the HIV testing window period

Unknown – Sero-Negative HIV Infections

This is what science cannot explain.

There are a group of people in this world, albeit extremely rare, who seem apparently normal in all ways but just do not develop antibodies against HIV when infected with HIV.

These people often progress rapidly into AIDS and are only diagnosed when they are in AIDS stage.

It is theorized that the problem is with the patients rather than the virus. This is because a genetically identical virus in a different patient can illicit an antibody response. In other words, if the same virus infects 2 different people, one will develop antibodies against it and not the other.

It has been theorized that this has something to do with the HLA make up of a person which determines how his/her immune system works. But to date, we do not really know what causes these patients to remain persistently sero-negative.

Although such cases has been described, they are very rare. Less than 1 in a million of HIV cases diagnosed.

How do we overcome this problem?

That is the golden question.

Unfortunately, many of these patients present in late stage AIDS because their diagnosis of a HIV infection has been missed all this while.

The 2 solutions we have are:

  1. P24 testing or Combo Test

These patients who do not develop antibodies against HIV will have a persistently high P24 level in their blood. So doing a P24 test will identify the infection.

This is very inline with the new HIV diagnostic testing Guidelines published in June 2014 by the US CDC which states that everyone should get a Combo test and not just an antibody test.

Click here for more info on the HIV Combo test
  1. RNA PCR (Viral Load) Testing

These patients who do not develop antibodies against HIV will have a very high HIV viral load. Often greater than 100,000 copies per ml.

There are 2 drawbacks with this test in Singapore:

  1. It is expensive ($600 to $700) in most clinics
  2. It cannot be done anonymously
Click here for more info on the HIV PCR test

In Summary

There are cases of people in this world who get infected with HIV but do not develop any antibodies. They therefore have persistently false negative ELISA tests.

These cases are very very rare.

There is no reason for you to doubt the ELISA tests that you have done. If your doctor tells you that your tests are conclusive and you do not have HIV, please accept that happy fact and move on.

If you cannot let go and require that added measure of reassurance, get a P24 test and/or an RNA PCR test.

If you still cannot let go, it is more likely you need psychological help rather than virological help.

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Related Articles:

HIV Window Period

HIV CMIA Test Accuracy

How long can HIV live outside the body

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Rapid Anonymous HIV Combo test at our Clinic

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About Dr. Tan
Dr. Tan graduated from the National University of Singapore in 2001. His residency was in the two largest public hospitals in Singapore; Tan Tock Seng Hospital and Singapore General Hospital.

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239 Comments

  1. Is a single non reactive 4th generation clia ab/ag test after 4 months of exposure conclusive?
    Do I need retest?

    • In my view, the HIV Combo test is accurate after 28 days. However as we are not privy to the details of how the test was conducted, we cannot verify the accuracy of your tests. Please seek clarification from the doctor who did the test for you.

      • Thanks a ton.
        It was abbot cmia test.
        My doctor still believes in 6 month guidelines.
        Do I need retest?

  2. i had a protected sex exposure with a CSW 3 years back and not sure if the condom broke

    My wife had a bout of fever, joint pains and rash after 3 months of my exposure. She has developed tingling pain over her body and a very painful heel for the last 18 months

    I am having a sore tongue for the last 1 year which is uncomfortable and manageable

    I did 2 Elisa tests in India and 1 rapid test 18 months after exposure and the tests were negative, Do i have HIV and need to test more as I am scred of the symptoms me and my wife are having . My exposure was in US and test in India ..is that nullifying my test results

    • Do you see a logical reason to doubt your test results? If not then you have to believe them that you are not infected with HIV.

      • Sir,

        I am worried because of the symptoms which are persisting.

        I did the tests in reputed hospital in India

        Please advise if I need to move on

  3. Negative at 65days after exposure, PCR blood test at 8weeks, 4months and 8months where 0.03,0.04 and 0.05,all in mg/dl -5 do i retest?

  4. just ask

    this is a very serious question so i m wainting your scientific and logical answer doctor 🙂

  5. just ask

    if the 4th generation tests and combo are cocnclusive at three months why some doctors in the world insist on testing after long period like 1year 2 years etc..??pls answer

    • I do not know. You will have to ask those doctors why they think that.

      • just ask

        The all say that in some people rarely antibodies acts very late and that could take months to some years..what is your answer doctor? May something like that can be true by scientific view?

  6. please reply sir !

  7. I asked an hiv counsellor in ictc in India And he
    siad you have to test upto 1.5 years for
    conclusive hiv result ! Please help. I am very
    terrified ! Please tell me when can I get a fully conclusive result ! My fourth gen test was negative at 3 months however…..

  8. hello doctor
    i had protected sex with indian prostitute in her
    periods. after sex i noticed blood on my pubic
    area and pennis shaft after an hour later. i
    became very worried. i had cmia combo test 3
    months post exposure…is my test conclusive. im
    really wortied sbout delay seroconversion cases
    ….shloud i do pcr rna or dna test….pleases

    • I can only say superficially that the CMIA Combo test at 3 months is conclusive. However, I am in no position to verify the accuracy of your results. For that you have to ask the doctor who conducted the test for you.

  9. Dear Dr. Tan & Partners,

    Thanks for the informative website and services. I just wanted to ask if I can be confident of negative 4th gen combo test results after 26 days?

    Also, are NAT tests at 26 days 100% accurate at detecting HIV? Any chance for false negatives?

    Thanks.

    • And just as a follow-up question please–does the NAT test detect both HIV 1 and HIV 2? Thanks.

    • Officially the 4th Gen HIV test is conclusive at 28 days.

      • Dear Dr. Tan,

        Thank you for taking the time to respond.

        Just an additonal question, how many days after exposure is the NAT test conclusive?

        Thanks again.

  10. Please dr tan
    Rna pcr 18th day and ag/ab 18th day after expouser negative again 36th day ag/ab negative day 21 to day 25 I have got diareah and neauseah my test could be false negative sir please answer me

    • To me your tests are conclusive. Please verify this with the doctor who did the test for you.

  11. Sir – I had done unprotected sex and give her blow job between during sex and after that exploser17th day pcr rna and antibody test was negative sir this test will be conclusive please tell me sir

  12. Hi Doctor,

    What are the odds of a false negative result after 5 months? The test I did was for my army FFI (blood test) so I do not know the type of test performed.

    • If I am not wrong, the Army sends its HIV screening tests to Quest Lab which by default, runs a 4th Generation test. So there is no reason to doubt the accuracy of the test at 5 months post exposure.

  13. sir i have almost every symptoms of hiv like fever rash stomach pain weight loss mouth alser stomach grugalling red pink resh in stomach nail pail etc and many more but my haiv rapid test in 66 days and 120 days is negative and hiv elisa 3rd generation test is also negative. Do i need further testing? Now i am getting my weight. But syill i have rash in stomach and ulser in mouth. Please help me doctoe.

    • Do you have any logical reasons to doubt the accuracy of the test result? Do you think that perhaps you are one of the very rare cases of sero-negative infections? As much as I agree that that is a possibility, the likelihood is extremely low. Since you are still concerned, you should see your doctor for a further discussion. Perhaps he can conduct an RNA PCR test for you. Please see your doctor for further advice.

  14. hi doc me again .. doc my exposure was insertive vaginal sex….. i got hiv test at 4.25 months and then at 167 days(23 weeks and 6 days) and my test result is negative ..in my early post you said that you dont have hiv….so can i move on with my life? is my negative hiv test conclusive? and do i need to retest?plz doc reply plzzzzz.

    • and it was unprotected insertive vaginal sex

    • plz doc its my last question… can i move on with my life ? is my 167 days negative hiv test conclusive? you said you dont have hiv….so it means i dot have to test again at exactly 6 months right doc? can i move on with my life? please doc answer its the last question i am asking from you .. plz answer doc

    • and doc i am going to marry now …. so my 167 days test is conclusive? or i need to test at exactly 6 months again? plz answer … you said you dont have hiv … so can i move on with my life and marry and make love with my wife without condom? do i have to test again at exactly 6 months?

  15. hi dear doctor , i had unprotected insertive vaginal sex with my ex girlfriend , she had boyfriend before me and she had unprotected sex with him , i tested anti hiv antibody test in the first affilliated hospital of xinjiang medical university,xinjiang,urumqi,china at 110 days (more then 15 weeks or more then 3 and a half months) and my test result is negative…so my negative test is conclusive? or do i have to retest at 6 months? as i heard some people seroconvert at 6 months…. ?what to do i am confused

    • It really depends on what test was done for you. As a general rule, all modern HIV tests (3rd Gen ELISAs) are more than enough to be conclusive at 3 months post exposure.

      • so if it was elisa 3rd generation then my test is conclusive? and what if it was 1st or 2nd generation elisa? if it was 1st or 2nd generation do i have to test at 6 months again?

        • As long as it is an antibody test, it is conclusive. (ELISA is an antibody test).

          • hi doc me again …just last question please answer.. is my negative hiv test at 167 days conclusive? can i move on with my life? you said that you do not have hiv… so can i move on with my life? do i need to retest? please waiting for ur answer .plz doc

      • what if it was 1st or 2nd generation elisa? if it was 1st or 2nd generation do i have to test at 6 months again?

      • and tomorrow will be 5 months and 3 weeks(164 days) so if i take test tomorrow at any antibody test will it be conclusive or still have to take test at exact 6 months?please reply doc.i am really tensed..

      • and doc i heard that 6 months is for those people who are immunosuppressed , or chemotherapy ,or antiviral drugs …. ad for normal people is 3 months is it true? and doc …….. i just remember and calculated the test i did before was after 4.25 months means 17 weeks…. so is it conclusive at 17 weeks or 4.25 months?

        • Yes it is conclusive. I do not think you need a re-test.

          • hi doc me again…. sorry just want last answer from you ,..is my 167 days negative hiv test conclusive? do i have to retest? you said that you do not have hiv …so can i move on with my life? plz reply do i have to retest or not? plz answer …its last question

      • dear doc plz reply me

  16. Dear Doctor,
    I would like to enquire something about HIV risk. 7 weeks ago I went to a massage centre in Malaysia for a 4 hands massage(2 ladies). I din’t know that these are dirty massage until the massagers offer sex services during the massage. They provided hard body to body massage to me nakedly and I refuse for further sex services immediately after they mentioned to me. I think they are most probably hiv+. I am worrying non-stop after the incident and think that they might intentionally passed their blood to my body cuts or scratches during the hard body massage as I have many cuts on my body due to mosquito bites. I had low grade fever starting from 5th weeks, average : 37.2c to 37.6c daily starting in the evening. I regretted a lot and swear that I will never visit any massage centre anymore. I have performed few tests as follow before the 3 months cut off period :

    1. Hiv duo ag/ab (10 days after exposure)
    2. Hiv finger prick rapid test (4 weeks)
    3. Hiv finger prick rapid test (6 weeks)
    4. Hiv duo ag/ab (50 days after exposure)

    All results came out negative, I am still paranoid for the final test in accordance with 3 months guideline . Could doctor please advise me whether my previous tests are conclusive or I must wait for 3 months to go on with my life?

    I sincerely wait for doctor answer, thanks.

    • First of all, you are not at risk of HIV in the first place. There was no penetrative sexual acts involved based on your description. Body to body contact, regardless of whether you have cuts or wounds or not, does not put you at risk of HIV.
      Based on your test results, you do not have HIV. If you are still concerned, please go ahead with the 3-month test.

      • Dear doctor,

        Thanks for your reply, my concern is whether the ag/ab test on 50 days is conclusive or not? Do I need to wait for 3 months to test again? I am suffering for waiting on that. Please help to answer doctor, thanks.

  17. Hi doctor

    Had 7 negative test 5 combo. Tested at your clinic om 15th day 25th day and 38 th day
    Also had negative 3rd generation Elisa at 40 days and negative 4th generation Elisa at 45 days.

    Still have a movable swollen lymp node under jaw only can feel when I touch . it makes me still worried.

    Tested negative fr all other std at 6 weeks

    What is the probability fr the results to change later at 3 months.

    Should I believe the results or shd still keep testing until 6 months. Do you still feel I am at risk.

    My exposure was a condom break with a person of unknown status one time vagina insertive

    What are the chances fr the results to change later.

    Regard

  18. Any answer please

  19. Hi Dr Six Six Long

    I had unprotected sex in few seconds and I had elisa test for antibody after 18 & 45 days and also I had combo p24 test for antigens and antibody after 26 & 32 days
    All are negative
    Does this test are conclusive?
    Do I need a further test?
    Regards

    • Sorry for writing Uncorrected name because my keyboard is changing the liters automatically
      I meant Dr liong
      Does my test are conclusive?
      Do I need a further test?
      Elisa Ab 18 & 45 days after exposure
      Combo Ab&Ag 26 & 32 days after exposure

    • Hi. Your ELISA tests at 18 and 45 days were not conclusive because ELISA test is only conclusive after 3 months. Your combo tests were conclusive.
      I do not think you need a re-test.

      • Thanks doctor
        After the unprotected vaginas sex I had influenza for 10 days and I had pain in my legs
        Are you sure I don’t need to any further test?
        I don’t know about the lady she working in massage center

        • HAving influenza and pain in your legs does not mean you have HIV. Thousands of people get infected with influenza every day. If you are concerned, go and do a re-test for the peace of mind.

          • So what is the possibility to result will be change after all this test?
            Today I completed 65 days
            Can I do elisa test?

            I am scared for changing of result

          • Today I went to laboratory and I had combo test after 66 days post exposure
            Just I call and ask about the result they said it’s normal
            So.does it conclusive?
            Do I need a further test?

  20. Dear Dr Liong

    I have tested for HIV antibodies exactly 3 weeks after high-risk exposure with the 4th generation test.

    I wonder what the likelihood of my 3 weeks turning out to be a false negative..

    Your response is very much appreciated.. Thank you.

  21. Billz

    Hi dr… Sii sik liong
    Thanks for great info…. I’ll do a 6 months test to be sure… So is 6 months combo test will be fully final in my case or hv u seen anyone take any longer than 6 months with hiv combo test in worse to cases..& one more thing dr my test looks p24 antigen as we’ll .. Which is a part of virus itself I think is that would be positive if no antibody produced by my body…thanks again and plz reply u r a big support for me plzz…

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  1. HIV Testing Fast Facts Infographic | HIV - […] 12 weeks (3 months) post exposure. This is because of the possibility of sero-negative infections. Click here for more…
  2. HIV 4th Generation Test Singapore | HIV - […] rare cases of people who are infected with HIV but never produce any anti-bodies. These are called sero-negative infections…

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