Testing types and subtypes, unusual people

Dear Dr. Handsfield,

I have read posts on this forum and noticed that your and Dr. Edward Hook's professional advice has helped people all around the world about their concerns on HIV testing and prevention. Specially some blog format answers of you could have lighten on unclear concepts like "window period" which are very appreciable.
When somebody tests nonreactive after the window period, two major concern may remain.
1) types and subtypes
2) unusual response to hiv

I know that most important line of testing for hiv is testing for antibodies. I also know that these are in two main categories, third and fourth generation tests and they are very sensitive and accurate.
In one of your answers in this forum you have described that these tests cover all types and subtypes of hiv but extremely rare ones can be detected by PCR RNA.
Also CDC indicates that these tests covers "nearly" all types and subtypes.
My main questions are:
1) Are third and fourth generation tests cover all types and subtypes including CRF subtypes?
2) If there is any extremely rare type or subtype which is not detectable by antibody tests, what is their rareness in terms of figures and percentages and is that belongs to any special geographic region?
3) When would you suggest PCR RNA testing for people in addition to third or fourth generation tests to detect extremely rare types or subtypes?

Another question is about unusual response of people to hiv.
1) Which people have unusual response, ie not producing antibody, very late antibody producing, etc.
2) How these people could be diagnosed?
3) Is there any clue to find them?

Your detailed answer on these issues, as before, could open the information space to breath better and If they would be in a blog type answer, it could help the most.

Thanks and appreciate all of your endeavors on this forum.

Best Regards,
Mike

[Edward W Hook, MD]

Welcome to the Forum and thanks for your kind words.  We try our best to help.  I'll address your questions below but please understand that the amount of space we can allocate is constrained by character limits recently set in place (with our encouragement) in order to allow us to address more questions in the limited time we have available.  

I'll go to your questions in a moment but first I will share a bit of our perspective on questions about unusual situations.  Your question is a version of what we call “what if” questions in which clients ask how can we be sure that they were not infected.  The fact is that science continues to provide new knowledge and new facts however, with the exception of very uncommon (there's that qualifier again) breakthroughs, this knowledge accumulates in very small steps which have relatively little impact to the advice provided to the average person.  Unfortunately the internet and the understandable tendency of scientists to promote the importance of their own work both work to feed the insecurities and concerns for most people.  There are exceptions to virtually every rule but they are, fortunately,  very, very rare.

Further, please note that current tests including both 4th generation tests and PCR achieve increased sensitivity for infection by testing not (or not only) for antibodies but for the virus or virus components, removing the issue of antibody response from consideration.  When persons have HIV, unless they are on therapy (and therefore are not infectious for others) the virus is present.

[Edward W Hook, MD]

Answer to your first and second questions below- ran out of space.

As for your questions:
1) Are third and fourth generation tests cover all types and subtypes including CRF subtypes?
Tests for HIV are designed to detect shared components of the virus and tend to cross react. While one can never say never, when unusual subtypes are present they typically provide at least "indeterminate" if not positive results.  Results that are indeterminate are then further evaluated.  Current testing just does not miss a meaningful proportion of infections.

2) If there is any extremely rare type or subtype which is not detectable by antibody tests, what is their rareness in terms of figures and percentages and is that belongs to any special geographic region?
If you read this question and think about it, you will appreciate that it cannot be answered.  You basically asked "if there are undetectable subtypes, how common are they and where are they?".  I can assure you however, that they are not common enough for virtually anyone to worry about.

3) When would you suggest PCR RNA testing for people in addition to third or fourth generation tests to detect extremely rare types or subtypes?
We do not recommend PCR tests for routine HIV diagnosis for the reasons we have outlined before and which I will not repeat.  When we evaluate indeterminate infections or carry out research, PCR is one of many tools that we use.

[Edward W Hook, MD]

Your other question was:
Another question is about unusual response of people to hiv.
1) Which people have unusual response, ie not producing antibody, very late antibody producing, etc.
2) How these people could be diagnosed?
3) Is there any clue to find them?

People who do not produce antibodies are very, very rare because their inability to produce antibodies cause them to die soon after birth.  Fortunately, this problem is quite uncommon.  People who do not produce some element of antibodies are typically discovered when other problems such as recurring life-threatening infections bring them to professional attention.  Again, for anyone who has reached adulthood to worry about such problems is not typically worried.

I hope these comments are helpful.  Follow ups will be limited.  EWH

[thankuverymuch123]

Dear Dr. Hook,

Instead of just labeling people "Worried Well", your great answers really works to diminish my concerns.
Just hope you a life full of health for you and your family.

Warm Regards,
Mike

[Edward W Hook, MD]

Glad I could help.  EWH