[Question #4822] Low gamma globuline vs. test sensitivity

25 months ago
Dear Docs,
Following an exposure that I have been told is no risk, I took a long series of Syphilis (antibodies) and HIV (4th gen), up to 3 months which all came back negative (previous threads).
Case was close, BUT while archiving all my test results yesterday, I fell on a generic blood analysis results from last April 2018 I took before an IRM / radiology exam: the protein electrophoresis results report highlighted that for gammaglobuline I was slightly below “normal” values:  10.7% (normal frame indicated in the report for comparison being 11.1 to 18.8). By that time I asked two different doctors and both told me “nothing to worry about, if something would be wrong, you’d be constantly sick. Your immune system works”. A few months later (sept 2018), I took a “commitment” HIV, etc. test prescribed by my girlfriend gynecologist, and more recently the series of tests described in my previous threads.
Because all tests I have taken were antibody tests, I am again really worried. Would you please be kind enough to answer the following questions?
1/ Can this reported “hypogammaglobinemia” somehow affect reliability or window period of all my previous HIV/syphilis testing, the latest being negative at 3-month mark (HIV-1, HIV-2, syphilis), or of the previous ones? Including for tests which do not look for antigens (HIV-2, syphilis)?
2/ is this condition able to prevent or delay antibody apparition or to lower them below detection threshold?
3/ Because all were different doctors, I never asked about possible interference about this and STI/STD screening tests. Should I go to ask him or return to the lab and ask for their opinion?
4/ Is there any alternative testing method I should go for to ensure I am HIV / Syphilis / HepX / etc. free?
5/ are my 3-month test still 100% definitive?
Many thanks for your answers.

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
25 months ago
Welcome back to the forum, but I'm sorry you found it necessary after Dr. Hook's repeated, science based reassurance. I reviewed your discussion with him.

Testing for immunoglobulins made no sense, unless you are being evaluated for something other than HIV, syphilis, or other conditons related to sexual exposures. In any case, that result really isn't abnormal, just a minor lab test variation. Slight hypogammaglobulinemia is not immunodeficiency. People with such findings have entirely normal antibody responses. Further, there are NO medical conditions that affect the reliability of the current HIV blood tests, or the tests for syphilis. Early in the days of HIV antibody testsing, i.e. with the earliest tests, there were concerned that serious immune impairment might delay positive test results, prolonging the window period. However, that was always an issue only with profound immune deficiency, of the sort that occurs with advanced cancer, potent immune suppressing drugs or chemotherapy, and so on. There were few if any reports that it ever happened. And there have been NO such reports with the current antign-antibody tests. Your test results are equally valid as for any other potentially exposed perosn.

Those comments cover your specific questions, but here are my explicit replies so there is no possibility of misunderstanding:

1,2) These are the same question in different words. The answer is no. (You do not have a medical "condition". You have a minor, insignificant variation in a blood test that should not have been done.

3) Get whatever other medical opinions you wish. I am confident they will agree with my comments above.

4) No additional testing is necessary and there are no additional tests that would make any difference.

5) Yes.

I hope these comments finally settle these issues for you. It's time for you to move on and stop worrying about all this.

25 months ago

Dear Doctor,


Many thanks for your swift reply. I never intended to challenge answers I’ve been given so far and hope you believe I am not questioning answers I’ve been given by either you or Dr Hook.


I am myself quite disappointing to notice that I have not been able to move on following all the pieces of advice I’ve been given.


Regarding the “hypogammaglobinemia” I was concerned about, just for you to know, this exam was ordered last year by my physician independently from any STI/STD consideration as part of a very generic blood/serum check. You perfectly cleared my concern by confirming it is kind of minor deviation which cannot interfere or lower confidence in tests HIV tests I later took in different contexts.


Just because I want to close and leave everything behind me, from all answers I got from both of you, and though I thoroughly selected sources, I come to the conclusion that I’ve been reading too much.


The worst aspect of this is regarding HIV-2 because when reading all threads, it appears it has not been deeply studied and since there is no antigen detection to consolidate antibody aspect of the test, in the end, it looks “less reliable” to non-experts like me.


1/ I did not receive PostEP, did/do not take medications, I am not treated nor suffering for any chronic illness nor cancer (no chimiotherapy), and I am negative for hepC. I understood there is NO medical condition or “what if” scenario that would let think an expert clinician like yourself that HIV1 or HIV-2 antibody appearance may be undetectable at 3 months. Right?


2/ The once (or maybe still in force) US CDC recommendation for 6-months follow-up after high risk exposure is outdated since 1st / 2nd generation tests are no longer in use and the only (two?) cases of seroconversion after 3-months were documented back in the 1980s when 3rd / 4th gen tests were not in use. No other documented case since with 3rd / 4th gen. Am I correct?


3/ Was not my case, but assuming one had an high risk exposure in a part of the world where HIV-2 is more common (central Africa), and he come to your clinic, would you consider a 3 month neg with 3rd or 4th gen 100% definitive with no need for follow-up beyond three months as well? Is the 3-month worldwide (conservative) gold standard?


4/ I remember a thread on another platform where you said to a forum user with a NEG test at somewhat 7-8 weeks, that even if he had voluntarily injected himself KNOWN HIV infected blood directly in his bloodstream, you would not recommend further testing and consider these results as strictly definitive. That’s the kind of strong image that helps me moving forward. Would this image apply regardless of the kind of HIV types one could have been exposed, including if this injected blood was known to be HIV-2 infected?


5/ In the same way I found out French specific guidance addressing  medical professionals (e.g. surgeons) that got accidentally in contact with blood as part of their medical practice (provided they haven’t been put on PEP), that HIV test are definitive 3-month after exposure. Do you agree?


6/ My 3-month mark 4th generation HIV (and previous ones) NEG testing exclude any kind of HIV infections, and results I got so far are “SOLID ROCK” and definitive proof that I have not been infected with neither HIV-1 nor HIV-2 because even if no HIV-2 antigen is screened with 4th gen test, all HIV-2 infection will be picked up without remaining doubt at 3 months through antibodies.


Many thanks for your additional comments, after which I hope I will feel no need to come back and better be focus on resuling my life with my beloved one without further concern of passing her something.

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
25 months ago
1) Your summary is correct.
2) Correct. CDC no longer recommends 6 month testing. To my knowledge no documented failure of 3rd or 4th generations to seroconvert later than 45-50 days, and virtually all within 6 weeks.
3) yes, I agree.
4) all correct.
5) Correct. Actually, 6 weeks for the AgAb (4th generation) tests, and probably for the 3rd gen tests.
6) All correct, in fact at 6 weeks, not 3 months. 

That concludes this thread.  Please note the forum does not permit repeated questions on the same topic or exposure. This will have to be your last one; future new questions about this exposure and HIV testing may receive no reply and the posting fee will not be refunded. This policy is based on compassion, not criticism, and is intended to reduce temptations to keep paying for questions with obvious answers. In addition, experience shows that continued answers tend to prolong users' anxieties rather than reducing them. Finally, such questions have little educational value for other users, one of the forum's main purposes. Thank you for your understanding.