[Question #7235] false negative 4th gen test

5 months ago

Thank you in advance for your help. Straight male who in 2014 had a high risk exposure. This was virginal sex with woman of African origin while on holiday in Spain. Complete condom tear only noticed at end. 100% exposure. Earlier that year I also had virginal sex with CSW (I am uk based) condom used no tear. No other exposures since. However, after that incident in 2014, I stupidly only took an approved 2nd gen home finger prick test and  continued with my partner afterwards ( I really don't know why I didn't go the hospital). Apart from a UTI in 2017, which cleared up with antibiotics , I have been well. But then in feb this year, I got a cough, bad chest and cold, which kept me off work for 3 days, and lingered for about 7-10 days afterwards. However, after this, thick white coating on tongue, red spots underneath, some pain. After research realized oral thrush, which is late stage HIV infection. It persists to this day. I have only seen Dr virtually and he prescribed x2 daktarin gel and then x1 nystatin, but have not been back since. Since then my health has been downward spiral. I have pain in my lower back and sides (kidney), which I had urine dip stick test which didn't show anything, sore throat on and off  for months, feeling dizzy, and some skin infections, and lots of spots with puss. I am not sleeping for the last 6 months. As the Sexual health clinics were closed due to covid, I did another two 2nd gen self test, which were both negative, but have no faith in, and eventually saw HIV Dr in June at hospital and got 4th gen lab test for hiv, and test for hep b, hep c, and syphillis. All came back negative. I told him of exposure and oral thrush, but he said to see my local Dr about it. I was surprised because oral thrush red flag As there is no walk in service it is appointment only, and they won’t see me again as test was negative and no further risks. However I doubt the results due to number of reasons: I could have been exposed to HIV2 which is prevalent in Africa and much harder to detect. I think I am late stage HIV with oral candidiasis  and I have suffered seroreversion (my antibodies no longer detectable). I am one of those rare cases of seronegative patients (I do not produce antibodies) . About 35 documented cases of seronegative cases in 2019 medical journal.

I am worried as my partner has been feeling fatigued for weeks now, has persistent cough and has foot fungal problems. I know I have passed it onto her and do not want her to get ill, so I need to know what is best test to take next? Another 4th gen to rule out lab error? I have booked an hiv-1 rna pcr test, which expect to be returned ‘positive’ but if hiv-1 virus is not detected what test can I take rule out hiv2? Please, I am losing my mind and need to be on ART as soon as possible. 

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
5 months ago
Welcome to the forum.

Some questions can be answered accurately based on only the title of the question. That's the case here:  false negative 4th generation HIV tests are exceedingly rare, if they occur at all. I am unaware of any credible reports that this ever has happened. I am not aware of any scientific report of 19 such cases and I suspect you're misinterpreting it. If you would like to provide a link or otherwise identify that report, I'll be happy to look at it.

Looking at your question, the main issue here is your belief that oral thrush always is due to HIV/AIDS. It is not; it happens frequently in healthy persons. I've had it myself. The HIV blood tests, especially the antigen-antibody (AgAb, "4th generation") tests, are among the most accurate diagnostic tests ever developed, for any medical condition. The results always overrule symptoms and exposure history:  no matter how typical someone's symptoms appear to be for HIV or AIDS, a negative AgAb test shows that something else is causing the symptoms. (And by the way, even if you somehow failed to produce antibodies, the antigen component of the test would be positive.) And beyond the apparent oral yeast infection, the other problems you list are very common in people without HIV and are not reliable indicators of HIV infection.

I would have recommended against an RNA test, but as long as it's scheduled, you probably should go ahead -- expecting it to be negative and perhaps helping convince you that you don't have HIV.  So do your best not to worry in the meantime!

I hope these comments are helpful. Let me know if anything isn't clear.

HHH, MD
---
5 months ago

Hi Doctor,

Thank you for your quick response. I want to say I totally respect the answer received from such an esteemed expert, and do not wish to question it, especially as a non-medical\scientific professional, but I still have doubts.

Firstly, in terms of the reports, I probably need to clarify. It was not about faulty 4th gen tests, rather reports on 35 persistently negative or intermediate results in HIV seronegative (or seroreversion) individuals. I think they all refer to antibody only tests and WB, and span a timeframe from 1994-2017, which I admit is a very small number for the number of years and tests. I think most (if not all) had late stage HIV\AIDS. Here is the link:

https://ideas.repec.org/a/abf/journl/v20y2019i2p14877-14882.html

and the PDF:

https://biomedres.us/pdfs/BJSTR.MS.ID.003423.pdf

Also, this article from HIV Dr in Singapore regarding false ELISA tests, although he acknowledges they are 1 in a million cases:

http://www.drtanandpartners.com/false-negative-hiv-elisa-test/

In terms of my prognosis, I must admit that Oral Thrush was the main driver, as lots of the literature points to being most common late stage HIV infection, and very common in HIV positive individuals. All the HIV websites I looked at seemed to suggest people were tested and diagnosed through oral thrush, and that unless you have taken antibiotics (which I hadn’t) or smoked a 100 cigarettes a day, then you had to be severely  immunosuppressed  to get it! I admit I didn’t sleep for a week after that, and that convinced me of HIV infection, but I have had other symptoms over the last few months as well as the ones I mentioned, such as lots of heartburn\indigestion, trouble swallowing, which may, in fact, be systematic candida? Plus dental issues. Together with my partner’s symptoms, it is a troubling, but somewhat compelling case.  

I guess I am worried that a) one 4th gen test isn’t enough. I always worry I could be that 'outlier', that 1 in 1000 that is not picked up. Although the two finger prick home self-test kits also check for hiv1\2 ab, and claim 99.7%  specificity, I am not convinced by them, and I am worried that condom split with woman of African origin in 2014, from continent with high very HIV rates, and high HIV2 rates, that I was exposed to HIV2, and the tests in Europe may not be sensitive to this? As well as the other reasons I have outlined (especially sero-reversion late stage HIV).

I guess after 6 months I am past the stage of ‘Am I infected?’ to ‘how do I get it detected?’.I just don’t want me (or my partner) to end up in A&E really ill and on death beds before I\we get diagnosed.  In terms of the RNA, I have paid to take this with private Doctor. To be fair, after the online consultation, he didn’t recommend the test, based on what I said, even though he said it would cost him money. He was just as confident in the 4th Gen test at public Hospital.  

I should get the results within 3\4 days of taking the test. I am not holding out much hope. However, if it is negative, as it is checking only HIV1 it probably still won’t be the end of my worries! Thank you for your time and expertise.

 

 

 

  

 

 

 

 

 

 

 

 

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
5 months ago
Thanks for the additional information and clarifications. Indeed, in rare cases HIV infected persons fail to produce antibody (at least the antibody detected by the standards tests; I believe they all make other antibodies). That's one of the beauties of the AgAb tests:  without p24 antibody, p24 antigen persists in the blood. As I said in my initial reply, I am unaware of credible rerports of failure of the AgAb tests when done sufficiently long after the last possible explsure (~6 weeks, or longer following PEP or PrEP that doesn't work). In other words, to my knowledge it is not true that 1 in a thousand (or any at all) have false negative AgAb tests. Your single negative test is conclusive. I'm guessing your 1 in 1000 figure comes from one or more AgAb test producers. Such statements result from a statistical calculation, not actual documentation based on patient experience. Anyway, you've had several such tests -- all negative!

And it is correct that when oral yeast infections (thrush) occur due to HIV, they are an indication of severe immunodeficiency and prolonged infection, i.e. overt AIDS. As a consequence, thrush is almost never the only or main symptom; it occurs in people who are otherwise obviously ill, usually with weight loss, unexplained fevers, and other opportunistic infections (certain pneumonias and cancers). Oral yeast in someone who is otherwise outwardly well is rarely if ever due to HIV.

Finally, I agree with the online physician you contacted. The AgAb tests (also the earlier 2nd and 3rd generation lab-based antibody tests) are highly automated and pretty much foolproof in any and all labs that perform them, whether an academic medical center, a private or public hospital, or a commercial lab.

Therefore, you can expect a negative RNA test. And your current test is effective in detecting HIV2, which is very rare anyway in most of the world. In the US, for example, most HIV2 infections are in immigrants from areas where it is common (central west Africa) or their sex partners. Very few cases are found in people with the standard sexual risk factors.

Threads are closed after two follow-up comments and replies. Let's hold off on further discussion until you've had the RNA test, at which time I'll be happy to answer any remaining quesitons.
---
---
---
---
5 months ago
Hi Doctor Handsfield,

I want to start off by stating how helpful this service is, and how grateful I am to be able to converse with such an expert as you. I am really grateful. I also want to thank you for your patience dealing with 'laymen' like me, who scour the internet then question the medical and scientific tests and opinions with research via Google! It must be tiresome when people like me are sending you links and journal articles disputing the above as if you don't know a thing or two about the subject yourself! 

As it is my last question I will try to use it judiciously. As you know, I have had a couple of 2nd gen home finger prick self tests (April this year), which were negative after 6 years potential high risk exposure.   I have also taken a 4th gen HIV lab test at Sexual Health Clinic in UK (June this year) that came back negative but I was worried due to symptoms and late stage HIV  that I may be a rare HIV seronegative infection or that seroreversion had taken place due to late stage illness and\or rare HIV2 infection. As you know, I went for a private HIV-RNA PCR test (against Dr's advice) and I have been avoiding the results for days as I was so convinced it would be positive. I have got them back (and will question this at the private Dr's where I took the test) but although the results came back negative (just as you said-phew!) and I am confused about the test. 

Now I don't know if this just relevant to the test itself, or the UK, so you may not be able to answer, but the results state:

MPX- HIV1/2 -HBV-HCV-PCR

HIV1\2 PCR: Negative
HCV PCR : Negative
HBV PCR: Negative

I am unsure what this test is testing  (yes, I should have clarified this with the Dr). Can I rule HIV1 out (unless I am an elite controller-but that is another worry!!?) Is this testing for HIV2 also?  If so, what is it looking for? I am sorry Doctor but the last 6 months have been hellish.  If there is another more conclusive test I can take for HIV2 then please let me know. I am not suggesting you recommend it, but I can't move on with my life at the moment. As you know my exposure was with female of African origin, and my limited knowledge is that HIV2 infections naturally have a lower viral load. As a colleague of yours posted in a reply to another post , I may be wanting to get among the 'weeds' in terms of HIV testing and false negatives, but I am really worried about this for me and my partners health.

Again, thank you in advance for your time and expertise.


H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
5 months ago
There's a lot here, especially for a follow-up question. But to the specific questions I discern:

"MPX etc..." means you had a multiplex PCR that looked for DNA (or RNA) for HIV1, HIV2, and the hepatitis B and C viruses. The negative results mean you are not infected with any of those 4 viruses. Note that this is the confirmatory result you were looking for for HIV2. 

You conclusively do not have HIV1 or HIV2.  You can rule both of them out. There is no more conclusive test available or necessary for either HIV1 or 2. That HIV2 often has a lower viral load does not have any effect on test performance or reliability. Elite controllers have low levels of immune deficiency and low speed of progression of immune impairment, but absolutely no difference in test performance in diagnosing HIV.

That you "can't move on with [your] life at the moment" is a cri de coeur that indicates a level of emotional distress that demands professional counseling. It simply is not normal to remain as anxious and fearful as you are in the face of the overwhelming scientific evidence that you do not have HIV and the repeated, reasoned, science-based advice and reassurance you have had from your doctors and this forum. I advise mental health evaluation and care from compassion, not criticism. Please take it seriously.

That concludes this thread. I hope you are able to move on with no further "yes but", "what if", or "could I be the exception" sorts of thoughts or questions. But I doubt you will, based on all you have said. Hence my advice about counseling. Good luck with it.
---
---
---