[Question #3838] HIV Window Testing Period 4th Generation AG/AB Test

32 months ago
Dr. Handsfield, 

First off, I just want to thank you for all the work that you have done in the area of HIV and STD research. I have a brother that passed away from HIV and so it is a subject that is close to my heart.

My question is: could you provide more information about your statement: "About a year ago, a comprehensive review of the performance of all available HIV tests (in the US) was published, which concluded that in rare cases the Ag/Ab tests require 6 weeks for conclusive results. At that time we revised our routine advice to 6 rather than 4 weeks."

After reading your responses to many questions on medhealth and other health forums, I concluded that the 4th generation test was conclusive at 28 days or more. I recently took a 4th generation test (29 days post potential exposure) and tested negative. However, after seeing your revision, I am a little concerned again.  

Can you talk about these "rare cases" where a six week test is required? I have a wife and two kids, including an infant, and therefore want to be absolutely certain that I am HIV negative. Thank you and God bless. 

H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
32 months ago
Welcome to the forum. Thanks for your question, your confidence in our services, and your kind words about our work. My condolences to you and your family for loss of your brother.

There really is nothing know about the "rare cases" that take more than 28 days (up to 6 weeks) for positive results. References to the review paper you refer to, and to CDC's editorial concurrence with the report, are below. The serum panels used by test manufacturers, CDC, etc were collected from patients over many years, from HIV infected persons in whom the date of infection was believed to be known and several specimens were available over a few weeks or months. However, for reasons of confidentiality, those data bases contain no information whatsoever about the patients, their actual risk factors, or how accurate the estimates of infection date might be. From all we know about the course of HIV infection, the immune response to it, and so on, it should never take more than 28 days for the Ag/Ab tests to become positive. My guess is that the estimated infection dates were wrong in a few patients. It's also reasonable to speculate that some may have taken post-exposure prophylaxis but didn't reveal that fact (in the days before PEP was approved and recommended). But there is no way to know whether these or other unknown factors may be involved.

https://www.ncbi.nlm.nih.gov/pubmed/29140890
https://www.ncbi.nlm.nih.gov/pubmed/29140891

Anyone with a negative Ag/Ab test result 4 weeks of more after the last possible exposure should take that as extremely reassuring, with almost no chance they actually acquired HIV -- even if they have to wait a couple more weeks for an officially conclusive result.

Sorry that no more information is available, but I hope these comments are useful. Let me know if anything isn't clear.

HHH, MD

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32 months ago
Thank you for your prompt response doctor. Just a couple of follow-up questions:

1. Based on your response, would it be accurate to say that if I have been tested 29 days after a potential exposure to HIV (29 days being 100% accurate) and that I have never taken PEP, that my results from a 4th generation test are conclusive?

2. I have read in a prior post that neither you nor any of your colleagues have ever seen a 4th generation go from non-reactive at four weeks to reactive at six weeks - is this true? And if this is true, then why have you been motivated to revise your position on when the test is conclusive (from four to six weeks)?

I suppose I am feeling some guilt and anxiety from having sex with my wife after the results of my 4th generation test at 29 days. I assumed that those results were conclusive. However, after reading your revised guidance, I feel a heavy uncertainty looming over me. 

3. What is your opinion on BASHH/EAGA's position:  A negative result on a fourth generation test performed at 4 weeks post-exposure is highly likely to exclude HIV infection.  A further test at 8 weeks post-exposure need only be considered following an event assessed as carrying a high risk of infection.

This is yet another interpretation on how to proceed with HIV testing. I'm sure you can understand how so many different conclusive dates and window periods can be confusing to the average lay person. 

I apologize for compounding questions like this, but it is rare for me to have the opportunity to ask questions like these to someone of your esteem. I thank you for your time in answering my questions and concerns. 


H. Hunter Handsfield, MD
H. Hunter Handsfield, MD
32 months ago
I agree exactly with all three of your statements:  yes, yes, and yes. (BASHH is perhaps expressing a bit of British conservatism in extending to 8 weeks for especially high risk exposures; 6 weeks is our view.)

Of course I understand how this shifting advice is a problem, but only for a small minority of persons. 99+% of people tested for HIV don't know or care about any of this. They have a test, and if they are told "it's negative, you're good to go" never ask about window periods, follow-up testing, etc. Don't interpret the questions and discussions on this forum as typical. They are highly shifted to the very worried/anxious end of the bell shaped curve.

Anyway, I hope the discussion has helped with your "looming cloud"!
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