[Question #2384] Genuine Clarity

46 months ago
Hello Dr's,

I will get right to my questions along with history of testing.

Testing done- 9 4th Generation Lab Based tests through Quest - All negative, first test being 23 days and then throughout at different time intervals up to 20 weeks (5 Months) + One GP test at my doctors office, i can only presume it was an antibody only test as i noticed it said Single Assay (It also came back negative at 224 days (32 weeks)

1. I would like a little clarity on if i can absolutely be confident that my tests above are conclusive and definitive regardless of risk?

2. I have read and read and feel over the past 9 months that this worry in all honesty is the worst i have ever experienced. One of the things i read about is the term Seronegative- What does this mean from your perspective?

3. Do 4th generations tests eliminate the concern that one may have in regards to believing the may be among the 25 confirmed sero negative cases throughout history? From what i understand, Seronegative individuals do not form antibodies for some reason, is this the benefit of the 4th generation test?

Logically in my mind i understand the science behind the tests and i feel perhaps 99% of the population would have forgot about this long ago, however it seems i am obviously somewhat still obsessed with this worry. 

Hoping for some clarity, 
Thank you for your time
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
46 months ago
Welcome to the forum. Thanks for your question.

Perhaps we can start with some information about the current HIV tests. They are among the most accurate diagnostic tests ever developed, for any medical condition. Given enough time after the last possible exposure, i.e. 4-12 weeks depending on the particular test or combination of tests, the results overrule everything else. No matter how typical the symptoms, and no matter how high the risk of HIV at the time of exposure, it is the test results that tell the truth -- never the exposure, never the symptoms.  To your specific questions:

1. Yes, you can and should be absolutely confident.

2. Seronegative is not precisely defined, but in general medical usage (and my own perspective), it means a negative blood test for antibody to whatever is being tested. In somewhat broader usage, it means negative results in the blood for detection of the infectious agent, antibody to it, or both. But because there is no precise definition, different users may have slightly different meanings for the term.

3. I'm not aware of a report of 25 confirmed seronegative patients with HIV. However, I'm quite certain that these involved antibody testing only, not antigen, RNA, or the antigen-antibody (4th generation, "combo") tests. In other words, the answer is yes:  the 4th gen tests have resolved this issue. But it isn't just those tests. Most false seronegative cases were for the very earliest antibody tests used in the first few years of the HIV/AIDS epidemic (late 1980s, early 1990s). Few if any cases have been missed by any tests developed and used in the past 20-30 years, including the stand-alone antibody tests.

I agree your questions suggest you are obsessed quite irrationally with all this. As you apparently recognize, it is not normal to remain so uncertain or overtly fearful when understanding the science and following all the professional reassurance you must have had, even before my responses. I hope my comments finally settle it for you. However, I fear they will not. By their very nature, obsessions are typically not resolved by rational understanding and analysis. If you find yourself still dwelling on it, your next step should be professional counseling or other mental health care. I suggest it from compassion, not criticism. Whatever you do, stop wasting your money on any more HIV tests.

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


46 months ago
Hello Dr,

Thank you for the response, it is appreciated. In regards to your comments, i just have a few follow up questions.

1. The 25 seronegative cases i was referring to was based off this article i read: http://www.medscape.com/viewarticle/724575_3?pa=1h1E2MKxMjTh0wrBUwTaA5NZukw1U%2F08PWHX61qK2h9b1MNh4jSE7HOtKAR%2BczgrLCEJNCrbkqLWYvqLrhntWA%3D%3D

- I am not sure if this is confirmed cases or what

2. Can i also disregard any symptoms i may get now or in the future without worrying about my incident from 9 months back?

3. Would HIV 2 also be concluded by my 8 month antibody test or my 20 week 4th gen lab based test?

4. I've read that the 4th gen lab based tests are now conclusive at 6 weeks vs. the 4 weeks (Read on this forum) Have you ever witnessed sero conversion past the 6 week time frame unless of course they put themselves at risk again?

I'd just like to hear your response on the above and i am literally going to put a wall on my thoughts as they pertain to this worry.

Thank you for your guidance on this matter.
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
46 months ago
1) Thanks for the reference. The actual review article was published in the journal AIDS in 2010. All the 25 reported cases occurred before 2010, 16 of them before 2000, before development of the modern (3rd generation) antibody tests; and all the reports were about being seronegative for HIV antibody. Probably all the patients in the report would have tested positive with today's 3rd generation antibody tests and/or the 4th gen (antigen-antibody) tests. So the report is not relevant to the standard HIV tests used today.

2) Your tests results prove that no matter what symptoms you have now or may get in the future, they are not due to HIV from the event 9 months ago.

3) Yes, the 4th gen (and 3rd gen) tests detect HIV2.

4) It isn't the tests that have changed, just somewhat better understanding that rare patients take longer than 4 weeks to develop positive results. Most of these probably are in situations where the exposed person was taking anti-HIV drugs, which delayed development of positive test results. I have never personally seen nor even heard of anyone whose 4th gen test took more than 4 weeks to become positive, and for sure never 6 weeks or more.

Thanks for your thanks. I'm glad to have helped.

46 months ago
Thank you for the information on my follow up questions. Since i am allowed one last post i will take advantage of your expertise.

1. What makes the 3rd/4th gen tests different than the ones used in the case study (link) that i sent. Essentially just want to know if their ability to catch viruses has increased?

2. I guess my worry/concern still remains considering my partner sometimes gets a cough that persists/has itchy eyes/sore throat and that keeps my anxiety high thinking that i still may have HIV and for some reason my 13 tests have been wrong. Correct me if i am wrong to think this way?

3. Are there cases in which P24 could be missed, i presume it could happen on one or two tests but how likely is it to happen on 10 tests (all 4th gen) up to 1 day shy of 21 weeks. I also had an antibody test at 32 weeks as mentioned before

4. Can i fully move on with 100% confidence that i am conclusive negative

5. Is there any need for a further test (you've already stated stop testing) and i know the answer but i guess this shows my level of fear and irrational thinking around this.

Thank you Dr, i will not be returning to this site in the future and will never put myself in this position again.

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
46 months ago
1) I think you misunderstand the study. The authors did not evaluate 25 persons with HIV and didn't test them. They reviewed the existing medical literature for reports of people with HIV who were reported to have HIV with negative antibody tests. Since most of them were reported before 2000, they could not have been tested with 3rd or 3th generation tests. With the development of such tests, there have been few reports of people with HIV with negative blood tests.

2, 4, 5) These questions already were answered: re-read my main reply above.

3) It is the antibody itself that makes HIV p24 antigen go away. Once antibody has developed, the antigen part of the test becomes negative. If for some reason antibody doesn't develop, antigen remains detectable; if is absent, antibody will be detected. Therefore, once the test becomes positive, the test remains positive for life.

When you re-read my first reply, concentrate on the closing paragraph in my main reply above, about counseling being your next logical step. You don't say what your exposure was, but my guess is you are reacting emotionally to a sexual decision you regret. Professional mental health care probably will be needed for you to get beyond this.

That concludes this thread. Please do not be tempted to start a new one about the same exposure and HIV testing. Best wishes and stay safe.