[Question #4788] 4th gen ELISA HIV test 9 weeks vs. HIV-2

27 months ago

Dear Drs,
I posted a question few days ago regarding Syphilis testing. I am sure my new question is anxiety driven, but think answer from an expert would help.

Along my syphilis testing, I included some HIV testings, respectively performed at 3 wks (day21), 4 wks (day 31) and one more at 9 wks(day 63).
All tests were ECLIA / MODULAR ROCHE HIV1/HIV2 antibodies + HIV1 p24 antigen.
In France, a negative HIV1/2 AbAg is considered to definitely exclude HIV infection provided there is no exposure in the 6 wks.

I know that HIV-2 is extremely rare, but my question here is relative to 4th gen test ability to detect / diagnose HIV-2 and of the 100% certitude delay, regardless of the (low) likelihood to have been in contact with HIV-2.

1/ Is time necessary to develop antibodies against HIV-2 type greater or different than for HIV-1? Are they some HIV-2 specifics that would lead to later antibodies appearance / seroconversion compared to HIV-1?

2/ Compared to 3rd gen, 4th gen tests include HIV-1 p24 antigen search, improving HIV-1 early detection. Which improvement(s) brought to 4th gen testing allows to definitely exclude HIV-2 as soon as 6 weeks compared to previous 3rd gen tests and previous admitted definitive results timeframe with Ab only 3rd gen test?

3/ Does a 4th gen NEG test at 6 weeks also 100% exclude HIV-2?

4/ What about my 4th gen NEG testing at 9 weeks: does it 100% sure rule out all kinds of HIV kinds/types infection? Do ALL people would have developed antibodies whether it is HIV-1 or -2.

Many thanks for your answer.
Kindest regards.

Edward W. Hook M.D.
Edward W. Hook M.D.
27 months ago
Welcome back to the Forum.  I'll be glad to comment.  The French guidelines for HIV test result timing is the same as it is here in North America - six results are conclusive.  This is true both for HIV-1 and HIV-2.  In answer to your specific questions:
1/ Is time necessary to develop antibodies against HIV-2 type greater or different than for HIV-1? Are they some HIV-2 specifics that would lead to later antibodies appearance / seroconversion compared to HIV-1? 
No, they are similar.  The natural history (i.e. progression time course) of HIV-2 is somewhat different (less aggressive) than HIV-1 but the time for development of antibodies is the same.  

2/ Compared to 3rd gen, 4th gen tests include HIV-1 p24 antigen search, improving HIV-1 early detection. Which improvement(s) brought to 4th gen testing allows to definitely exclude HIV-2 as soon as 6 weeks compared to previous 3rd gen tests and previous admitted definitive results timeframe with Ab only 3rd gen test?
The main improvement in going form 3rd generation, combination antigen/antibody tests is the addition of the antigen which allows for earlier detection.  There may be slightly different changes to the antibody detection methods but what they may be is proprietary and not known to me.  

3/ Does a 4th gen NEG test at 6 weeks also 100% exclude HIV-2?
Yes

4/ What about my 4th gen NEG testing at 9 weeks: does it 100% sure rule out all kinds of HIV kinds/types infection? Do ALL people would have developed antibodies whether it is HIV-1 or -2.
Yes, the  results are conclusive at 6 weeks and beyond.  No need forfurther testing beyond six weeks.

I hope this will address your lingering questions and that you will now be able to move forward without concern.  EWH
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27 months ago
Many thanks for your answer.

To be honest, I understand rationale for 6 wks (compared to 3 mo) definitive results for HIV-1 because it benefits from p24 antigen detection. For HIV-2, I am not 100% reassured since while Sweden or Germany reduced to 6 weeks, they also state that because of HIV-2 longer window period and lack of data, 3 months should still apply if HIV-2 exposure is suspected.

1/ Based on your answer, I can understand, that HIV-2 will be detected by 4th gen with the same level of certitude than with 3rd ab only test, i.e. 100% by 8 weeks (not 3 months). Is that correct?

2/ Do you confirm you never heard of 8w+ seroconversion for HIV 1 or 2 and that my 9 week 4th test is more than definitive regardless of the nature of the exposure?

3/ My exposure was protected BJ with a minuscule "pinhole" hole on the side detected when water testing after encounter. I know saliva is not infectious, but had it been vaginal sex (it was not) would you consider the event as protected because of the almost non existant contact surface? I guess exposed surface and friction play a role in HIV transmission?

4/ Is there any difference in transmission risk/mode with HIV-2 compared to -1. I mean zero risk when being given BJ, for all known types of HIV?

5/ I was thinking of a test at 3 mo. to close the case but I am now afraid of false positive possibility. How often is that with 4th gen ELISA, 1 out of 1000?
(I found this kind of figure and find it enormous compared to the level of street it may generate waiting for confirmation WB)

6/If I haven't be subject to false positive so far (I took roughly ten times the same test/Roche modular Eclia, in the same lab over the past few years), could that tend to prove that I am not likely to generate false positive at my next testing?

Many thanks for your answers to my multiple questions that I will try not to further comment.










Edward W. Hook M.D.
Edward W. Hook M.D.
27 months ago
I'm sorry the you do not feel you can accept science-based, national recommendations.  To be clear, typically, antibody infection following any exposure that will elicit an antibody reaction begins around two weeks after exposure and is detectable 6 weeks after exposure. this is the case for HIV-1 or-2, syphilis, hepatitis, the influenza vaccine, etc.  This is a scientific fact.  As for your follow-up questions:

1.  Correct, see above.
2.  Correct for currently available tests.  Early on, with 1rst and 2nd generation tests, there were occasional (but rare) failures.  
3.  You are correct about the role of friction.  We discount the "water test" as it is inherently reliable in a used condom and the expansion due to the presence of water in a used condom may lead to pin-hole leaks.
4.  No difference that I am aware of.  
5.  The chance of a false positive test result is certainly less than 1 in 1000, probably substantially lower.  The Western blot is an out of date test.
6.  the fact that you have not had prior false positive tests does make it someone less likely, on average, that a repeat test would be falsely positive.  

I hope these further responses are helpful. EWH
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27 months ago
Dear Doctor.
Many many thanks for 200% clear answers which are conclusively reassuring to me. As said, and because your answers cannot be clearer to me, I won't further ask. All my blessings for this wonderful service and foe sharing you expertise. Kindest regards.

I let you close this thread.
Edward W. Hook M.D.
Edward W. Hook M.D.
27 months ago
Thanks very much for your thanks.  I'm pleased our Forum has been helpful to you.  Take care.  EWH---