[Question #6033] "Second" HIV Window Period

Moses Isaiah
18 months ago
Good day Doctors:

I've returned with another question. I should preface my question that I have been following Dr. Hook's advice of only reading reputable sites regarding HIV such as the CDC's website. 


"We describe an HIV-1 primary infection with a second diagnostic window of 18 to 34 days on a fourth-generation immunoassay, which would have been missed using some current algorithms. Caution must be exercised when fourth-generation HIV-1 immunoassays are interpreted in isolation, and additional testing should be considered depending on patient risk assessment."

There was also a footnote: "The Abbott Architect HIV Ab/Ag Combo remained nonreactive from day 7 through 24, becoming reactive at day 35." Also, I observed that the Determine HIV 1/2 Ag/Ab Combo remained only turned reactive on day 49. That said, here is my HIV exposure and test history:

17 July 2019 - Possible exposure to HIV, presumably partner had a high viral load.
14 August 2019 (4 weeks post-exposure) - SD Bioline HIV 1/2 3.0, nonreactive
29 August 2019 (6 weeks post-exposure) - SD Bioline HIV 1/2 3.0, nonreactive
09 September 2019 (54 days post-exposure, around 8 weeks) - HIV-1 Antigen and Antibody/HIV-2 Antibody Screening Test, nonreactive

This worries me because, despite the CDC's guidelines, this particular study suggests that there may be a significant window period, at least for the Abbott Architect test, which may be my test (the doctor did not tell me which "brand" they used). Dr. Hook and Dr. Handsfield dismissed the notion of a "second window period" as an internet myth, but finding this particular study is making me doubt the conclusivity of my 8-week 4th Gen HIV test. 

Thank you for clarifying, doctors!
Moses Isaiah
18 months ago
As supporting details, I'm quoting another passage from the article:

"Although it is generally regarded as rare, there are many published cases where at least one fourth-generation assay has failed to diagnose an HIV-positive patient on at least one test date. In some cases, this may be due to the presence of a second diagnostic window, defined as a period where a fourth-generation assay becomes nonreactive after the antigen component drops below the limit of detection and before the antibody component exceeds the limit of detection. One case report describes a permanent failure to detect antibody with two fourth-generation assays in an HIV group O infection. Other cases are possibly due to a primary diagnostic window caused by relative insensitivity of the antigen detection component compared with assays such as those for RNA detection (4) or for p24 antigen. The literature describes numerous cases where fourth-generation assay failures could conceivably be due to a second diagnostic window."

In 2005, a similar study was published by Speers, et. al titled "
Combination assay detecting both human immunodeficiency virus (HIV) p24 antigen and anti-HIV antibodies opens a second diagnostic window" (Speers, et. al. 2005) where the "second" diagnostic window was during the first nine (9) days:

"Although it is likely to be rare, this phenomenon has also been reported for other fourth-generation HIV immunoassays and has implications for the reported diagnostic windows of these assays."
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
18 months ago
Welcome back to the forum.

Thanks for the case report. You have researched the topic of secondary window with the AgAb (4th generation) HIV blood tests more thoroughly than I have. But here are some factors you may not have considered. First, report of a single rare case doesn't mean it's a common or worrisome problem. Indeed, the authors would not have reported this patient unless it were unusual. Second, it's 5 years old and on a quick literature search, I find no other reports since then. Third, the prior reports suggest that the problem has not been consistent between the various AgAb tests, and when test manufacturers become aware of problems with their tests, they often tweak them to correct the problem. For example, a couple of years ago there was a brief time when the Abbot Architect® test was having a problem with the antigen portion of the test, so it really behaved as if it were a standalone (3rd genration) antibody test. However, Abbott quickly corrected the problem, and the test now performs as designed. Similar corrections may have occurred with other tests; most such tweaks are kept confidential by the manufacturers.

I am unaware of any HIV testing services or experts who have ever had a patient who exhibited a secondary window. And if it still occurs on rare occasions, almost certainly even the second window is closed by 6 weeks and certainly by 8 weeks. Your apparent symptoms also do not concern me. The symptoms of acute HIV infection result from the body's immune response to HIV. Therefore, everybody with symptoms caused by HIV has a positive antibody test (including the AgAb tests). Even on rare occasions when time to seroconversion may be longer than average, a negative test more than a few days after onset of symptoms proves the symptoms are not due to HIV.

The bottom line is that your test results are valid:  for sure you do not have HIV. But of course you are free to get retested as frequently and at whatever intervals you like. Your doctor's advice to be tested once more after 12 weeks is not unreasonable, given your exposure to a known infected partner -- even though it is over-conservative. If you decide to do that, I am 100% confident that result will also be negative. It is clear you did not catch HIV.

Finally, in response to your question, I have emailed a nationally renowned HIV testing expert for his comments about secondary windows. I'll post a follow-up comment after he replies. In the meantime, I hope these comments are helpful and reassuring, as intended.

HHH, MD
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Moses Isaiah
18 months ago
Thank you for the reply Dr. Handsfield. Though I have to say while I did not initially mention of any symptoms, I do have the occassional pains in several places where my lymph nodes are (however my infectious disease doctor checked them and told me they were probably psychosomatic).

In the meantime, I can wait for the additional details. I hopeit only serves to strengthen my tests’ conclusivity, particularly my last 4th generation one. Thank you for the reassurances, doctor. 
H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
18 months ago
You described symptoms that concerned you in your previous thread.

The HIV testing expert responded to say that a secondary window with AgAb (4th generation) testing is extremely rare, and may no longer be a problem at all. The most recent case, i.e. the link you provided, was of a sort that probably applied to only a single brand of test (not he one you had, Bioline); and that even that test may no longer be a problem. Further, in the recent report and the prior ones that publication refers to, other tests easily resolved any uncertainty that briefly was present due to a secondary window.

Which brings me to my final advice and suggestion:  Most phyisicans caring for a patient with a high risk exposure, such as unprotected anal sex with a known infected partner, would have done a test for HIV RNA in blood ("viral load" test). That test is most useful about 2 weeks after exposure, which might be why your doctor didn't do it initially. At this point, it really doesn't matter, except possibly for reassurance:  if a viral RNA test were done now, it would prove with 100% certainty you do not have HIV and are not experiencing a secondary window. However, your current results are so reliable that this test is not necessary from a medical perspective. On the other hand, in proving you don't have HIV, you would no longer need another AgAb test at 12 weeks or any other time. You might discuss this with your doctor.

That completes the two follow-up comments and replies included with each question, and so ends this thread. Please do not be tempted to ask a third question on this exposure and your concerns about HIV testing. The forum does not permit repeated questions on the same topic or exposure., and future new questions along these lines will be deleted without reply and without refund of the posting fee. This policy is based on compassion, not criticism, and is designed 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.

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Having said all that, I thank you for raising this issue, which has elevated my expertise on the topic. As a result of this discussion, I and Dr. Hook will acknowlege that secondary windows have rarely occurred, although they remain (and always were) exceedingly rare and not pertinent to the large majority of questions we receive on this forum.---
Moses Isaiah
18 months ago
Thank you doctor for the reassurance and the reply. Have a great day!