What really is UND?

[BelB64]

I follow EVERYTHING I can about Hep C as I have a relative with it and I wonder about the following: When is UND REALLY UND? I ask this because when one is deemed UND 6 months after tex the chance of this reversing is quite low. Why then when one is UND after 4, 6 12 or 20 weeks into tex is there is a possibility of relapse or breakthrough? If there is no virus then there is no virus. Is UND at the earlier stages not really UND? Wouldn't it be great if there was a viral test that was SO sensitive it could measure the virus to the smallest possible measurement. Then whatever the measurement at true UND after tex could be compared to measurements during tex. If someone at week 7 for instance measured the exact measurements as someone who has officially cleared , they could possibly stop tex early.

[BelB64]

Thanks for all your input

[Rockerforlife]

You sure cleared up my question...thanx.

[portann]

The link you sent is really good. I found a newer 2007 study on the site that confirms the 2000 one:

Abstract
The efficacy of interferon therapy for hepatitis C virus (HCV) infection improved remarkably. However, virologic relapse occurs in a substantial proportion of patients with virologic response (defined as an HCV RNA level below 50 IU/ml at the end-of-treatment). A highly sensitive RT-nested PCR assay capable of detecting almost a single copy of HCV RNA and a real-time RT-PCR assay to quantify HCV RNA down to 120 copies per ml were developed. The RT-nested PCR assay showed that 1 IU of HCV RNA is equivalent to 12.2 copies. For 28 patients with virologic response (12 relapsers and 16 sustained virologic responders), week-4 and end-of-treatment plasma samples were retested. At week 4, HCV RNA was detected by the RT-nested PCR and qualitative COBAS Amplicor HCV version 2.0 in 8/9 (89%) and 6/9 (67%) samples from relapsers, and in 4/16 (25%) and 2/16 (13%) samples from sustained virologic responders, respectively. End-of-treatment samples with HCV-negative by the qualitative COBAS Amplicor were positive by the present assay in 4/12 (25%) of relapsing patients and 0/16 (0%) of sustained virologic responders. The viral levels detected by the present assay in the Amplicor-negative samples were 3.5-17.3 copies/ml, which is below the detection limit of COBAS Amplicor. In conclusion, the highly sensitive RT-nested PCR assay can predict sustained virologic response at week 4 and virologic relapse at the end-of-treatment more accurately than COBAS Amplicor, suggesting its usefulness in monitoring antiviral therapy for HCV infection. J. Med. Virol. 79: 1113-1119, 2007. © 2007 Wiley-Liss, Inc.
(http://www3.interscience.wiley.com/search/allsearch)

I'm definitely worried. I think I'll order pizza.

[portann]

Thanks, guys.

I always did intend to travel four hours return to get a more sensitive test during tx but never mustered up the initiative. So here I am, heading into week 42 and only ever tested down to 50 at weeks 4, 12 and 24. Laugh!!

At any rate, the meds don't seem to bother me as much these days as the uncertainty of the outcome. It really was a hell of a lot of work, this treatment, so I'd hate to think I blew it because of the wrong test.

Anyway, the deed is done and the cards are dealt.

Port

[geterdone]

I follow EVERYTHING I can about Hep C as I have a relative with it and I wonder about the following: When is UND REALLY UND?

*UND = non circulating virus in the blood stream.

I ask this because when one is deemed UND 6 months after tex the chance of this reversing is quite low. Why then when one is UND after 4, 6 12 or 20 weeks into tex is there is a possibility of relapse or breakthrough?

*Why then when one is UND after 4, 6 12 or 20 weeks

Because the meds are at maximum strength or close to it with in the first four weeks of treatment or longer depending on a host of variables but taking the 4 week mark and UND means there are no circulating viruses floating around in your blood system. Does that mean you are free of the virus, No. The virus may be imbedded (or hiding) in you organs and/or peripheral blood but not in the circulating blood. Being UND later than 4 weeks means that the virus may be occult strands or it could be that the Viral load could be higher and takes longer to eradicate or you may be insulin resistant or a host of other reasons.  

*If there is no virus then there is no virus. Is UND at the earlier stages not really UND?

No, the initial Viral Load has been knocked down below the detectable sensitivity of the PCR being used as explained above. The real work begins for the most part after UND is reached, the mop up of the cleaved virions and any occult virus or other resistant mutants that have not been eradicated in the initial phase of eradication which is why treatment can go as short as 24 weeks and as long as 72 weeks and beyond.

*Wouldn't it be great if there was a viral test that was SO sensitive it could measure the virus to       the smallest possible measurement.

The most commercial PCR to date is the one that goes down to <2 but it would be great if there was and absolute 0 test.

*Then whatever the measurement at true UND after tex could be compared to measurements during tex.

You will always carry the antibody of hepc and the virus itself but the immune system for the most part will keep it in check.

*If someone at week 7 for instance measured the exact measurements as someone who has officially cleared, they could possibly stop tex early.

No, but some lucky ones have been able to stop early and go on to SVR but I am sure they sweat the bullets in the waiting period. But unfortunately most are not lucky enough to achieve the feat.

[Rockerforlife]

It only makes sense to me if you have a the higher sensitivity tests <2 to <5....your odds of staying are better....

[apache1]

hey portann, here ya go

Here is one abstract I bookmarked for future reference...wish I did this to more abstracts. My bookmarks under my health folder is off the page lately. Got to figure out a new organization system for my hcv related topics,

http://www.ncbi.nlm.nih.gov/pubmed/11003628?dopt=Abstract

apache

[mikesimon]

No. Many people are undetectable per a very sensitive test and go on to relapse. This fact used to enter into discussions about occult virus but I don't think that it's determinative or really relevant to that issue. Why people relapse is an issue that to my knowledge has not be resolved but if there was any virus remaining after treatment then replication would result in relapse. Perhaps it is that simple - the tests don't have a zero sensitivity - they do not say that no virus remains. But I don't believe for a second that it is occult virus that is the cause of relapse.
Mike

[portann]

Does that mean that 65% of the relapsers had no detectable virus with the more sensitive tests but relapsed anyway? Would that would mean that 65% relapsed from occult virus?

If anyone has the link to that study, I would appreciate it very much.

TY,
Port

[Marc1955]

Wow, it's going to be hard for me to find the study at this point. As I recall, the number was 35%. That is, 35% percent of the relapsers in fact had low but detectable levels of virus.
If I find the link, I'll post it.

[portann]

Marc: "A study was conducted a few years back in which they ran blood samples that had previously been shown as UND at <50 through a more sensitive test. A sizable percentage of the relapsers in fact has detectable virus, but at less than the 50 iu/ml threshold."

Do you know what the 'sizable' percentage was? Thirty or forty percent?  Would you have a link to the study?

TY

[Rockerforlife]

Again....this virus does whatever it wants....it out right evil....seems like  more add more that to beat this is just a roll of the dice and hope we dont turn up snake eyes

[Marc1955]

There are two separate issues: nygirl17 is correct – less sensitive PCR's can show a false UND. A study was conducted a few years back in which they ran blood samples that had previously been shown as UND at <50 through a more sensitive test. A sizable percentage of the relapsers in fact has detectable virus, but at less than the 50 iu/ml threshold.

However, that being said, a certain fraction of people who are shown to be UND using even the most sensitive tests relapse after concluding treatment. People mistakenly think that when you eliminate the virus from your blood you've eliminated it. This unfortunately is not the case.

[nygirl7]

But a more sensitive test (<2 or <5)  might have a better chance of PREDICTING a relapse than a <615 or <50 tests"

Yes.  Had my doctor given me the <615 test at week 4 I would have believed I was UND and it would have altered my entire course of treatment (extension, double doses).  But because he gave me the most sensitive test it was clear I was NOT UND at 4 (count of 411) or 12 (count of 419) but then at week 24 with my <2 test I was UND all the way down.

UND and it's sensitivity is one of the most important factors there is. (At least to me who would have most likely not gotten SVR because I would not have known to extend to 72 weeks).

[charm27]

Really liked your explanantion in laymans terms with regard to Thomas's english muffins! Excellent!

However if they were generic muffins there would be less nooks and crannies! ( still the same outcome though) LOL

Seriously...you gave an excellent answer.

Charm27

[apache1]

Rocker,
No

No test will change if you are going to be svr or not.
But a more sensitive test (<2 or <5)  might have a better chance of PREDICTING a relapse than a <615 or <50 tests.

Maybe in certain situations, depending on what you do with the results of the test, this could maybe help you achieve SVR.
If at 12 week test (or eot) you showed minimal vl on a very sensitive test, (that does not show up on a less sensitive test) you might be able to tweak soc to a longer duration, or maybe add Alina, or up the riba, extra inf, etc, to help you clear the very small amount of remaining circulating virions.

apache

[Rockerforlife]

Are you saying the more sensitive the test is,odds are  SVR increased ?

[apache1]

Well said Marc. Flguy

BelB64,
All viral load tests are not created equal.

Imho it is very possible for a test to miss a very small amount of circulating copies.

Only 1vial = 1 ml of blood is tested. It could be clear...or it could contain just 1 VIRION even if it is tested to be <2 iU/ml
Or like HR said, figure a very small fish pond with 100 fish in it. Now you scoop a bucket out and no fish, scoop out 10 buckets now you got one fish.

So if you get one fish(virion) per 10 buckets(10ml) then compute that by 1800 ml of serum in our bodies, and you get maybe thousands of virions circulating even if you are under  <2 VL test. Now imagine a <615 test, how many fish(virions) could be swimming around in serum?

The more accurate/sensitive the test, the better the chance you are
'more UND'

Some older test go only to <615 uI/ml

others go to <50
others go to <15
others go to <10
others go to <5
others go to <2

Quest advertises their Heptimax <5 test as being able to accurately predict relapse in a percentage of PCR HCV negative patients. I am sure the <2 NGI LabCorp test would do similar compared to less sensitive tests.

apache

[Rockerforlife]

UND and SVR(cured) are not  really the same ....to be SVR(cured) you have to be UND for 6 mouths.

[FlGuy]

When I read your question I was going to draw a comparison to an historic event that begins today.  With the question 'Is there another earth-like planet in the universe?' you really can't know unless you look at the entire universe. But, you can make guesses. If there are a 100 Billion stars in the Milkey Way and there are billions of galaxies in the universe, you could probably take a guess that the chances of another earth is a distinct mathermatical possibility.
The blood draw to determine the presence is a very small amount of the blood floating around in you.  In fact, the results are reported as the number (or units) in a milimeter of blood. And, you have about 5,600 milimeters of blood floating around in you that are not tested. Plus a lot of other places for the virus to hang out.
But, the plantet-start-galaxy-universe example is bad analogy, although though-provoking.
A better example is to think of your body, relative to virus detection and virus hiding,  more like an English Muffin.  If you slice an English Muffin and put it on your kitchen counter you could try to count all the nooks and crannies.  You come up with a number.  You ask your spouse to count all the nooks and crannies too.  Would he or she come up with the exact number as you?
Now, leave the English Muffin on the kitchen counter for a few months.  After about 12 months pick up that dry and brittle English Muffin and crumble it in your hands until all the dust and crumbs fall in a pile back on to the counter. How many nooks and crannies are there now?

[Marc1955]

This is one of the most confusing aspects of the HCV treatment. When one is undetectable, that means that no virus can be detected in your blood stream. However, mutant strains of the virus can still be residing in your liver. When you stop treatment, the mutant strains revert and the HCV quickly reestablishes itself.

So the issue is not really the sensitivity of the viral tests. The current tests are very sensitive. All treatments that I am aware of for HCV involve staying on the medication after the virus is cleared from the bloodstream in order to purge those mutant strains that might be lurking in the liver.