HR, Jim, mremeet, Goofy Dad, anyone that has knowledge of pcr testing?

[prettydamscared]

Hi everyone,

Some of you have been following the saga of my "29" at week 12 as well as APK's.  I do think/hope my 29 at week 12 is an "artifact" or false positive but for my own peace of mine, I want to comfirm that by getting the most sensitive and accurate pcr test available.  Asked my doctor about it yesterday and the study can't provide one more sensitive than the one we've all been discussing but he told me I was welcome to get one on my own.

There's a lot of confusion in my mind surrounding these tests.  Searched the archives and found something Goofy Dad posted in Nov.06

http://www.natap.org/2005/HCV/122805_04.htm

Conclusions: Among patients treated with combination therapy for chronic hepatitis C, the TMA test detects HCV RNA in all specimens that are Amplicor-positive, as well as an additional 21.6% that are Amplicor-negative. The increased sensitivity of the TMA test can be helpful in identifying patients with low levels of HCV RNA who are likely to relapse when therapy is stopped. Furthermore, among patients with EVR and a negative Amplicor test at W20, persistent detection of HCV with the TMA test during therapy predicts failure to achieve SVR.

*FDA-approved for detection of HCV RNA as evidence of active infection.

Can someone explain to me like I'm five years old what the above means. Also, HR posted on 11/12/06 the following:

(Continued below)

[jmjm530]

It doesn't matter what kind of test you take EOT or post tx as long as it's sensitive enough. Ideally 10 IU/ml or less. The reason you here so much about "TMA" is because in general they are very sensitive. However, I believe there are equally sensitive PCR tests from LabCorp (HR will correct me if I'm wrong) for example, which are just as good. So you know, both of the tests I mentioned in the previous post use TMA technology.

[prettydamscared]

There's a lot to learn and I'm slowly, ever so slowly, getting there.  Geeesh, I just got diagnosed in April and feel like I've practically earned an hcv degree since then.

Thanks for all your explanations and help.  They are much appreciated.

Char

[neptune235]

Heh!  Yep...belt AND suspenders...just my OCD shinin' through!

[neptune235]

Ahh...I meant to add, at the conclusion of my second tx, 6months of peg and riba, I was 0 on my quant, and pos on my qual.  This was 4 years ago or so, and the detection limit of the quant was <600 (don't know what the limit on the qual was, but obviously, lower than that.)

[jmjm530]

Given the different sensitivities of the tests you took, taking both a qual and a quant made sense. In my case both tests had a sensitivity of 5 IU/ml so the reason I took two was not because of sensitivity but because I wanted to rule out lab error -- be it a false positive and equally important a false negative.

[mremeet]

Char, I think all the referenced study is saying is that using the most sensitive test available, both to validate EVR status and to verify UND status at the end of treatment, could be of critical utility to the patient undergoing treatment (not surprisingly). And the reason this is true, is because the referenced "normal" method of testing (via the Amplicor test) only had a sensitivity of 50-100 IU/ml, whereas the preferred (and recommended) method of testing was the TMA test with a much higher sensitivity of 5-10 IU/ml.

So all they're saying, is that if the relatively insensitive Amplicor test (as used for this particular trial) is relied upon solely, there will be a certain number of people who will fall between the cracks and relapse at EOT. By that I mean there will be a certain percentage of people who will test negative at the end of their normal (and prescribed) treatment cycle according to the Amplicor test, but in actuality will still have persistent low level virus present - which will then be responsible for their subsequent relapse. And if that fraction of "Amplicor negative at EOT relapsers" had been tested with the much more sensitive TMA test, then most of them would have been identified as still being actively infected (albeit at a very low level) at their normally planned EOT date. And if they were aware of their low level HCV+ status, they could extend their treatment for a longer period of time. This would obviously greatly enhance their probability of achieving an SVR, instead of relapsing like they otherwise would by choosing to conclude their normal course of treatment solely based on the less sensitive Amplicor test results alone.

So it's really just a common sense assertion that we should be tested with the most sensitive test available prior to halting treatment. Something I know you're already well aware of, and is sensibly why you're raising the issue now. My take on these VL tests is that their sensitivities have been evolving rapidly in recent years. Apparently just a few years ago, a sensitivity of 50-100 IU/ml (as for the referenced Amplicor test) was the (commonly accessible/used) cat's meow. And before that, even less sensitive tests were what was used. Our doctor mentioned that the original Pegylated IFN trials (several years ago) were conducted using a test sensitivity of ~600 IU/ml (if memory serves). So it seems to me that these tests have been evolving and advancing rapidly in their ability to resolve lower and lower viral levels in recent years. And I think the study you referenced above is just another informative stepping stone to make clinicians aware of the value of these more sensitive tests for the direct and very significant benefit of their patients (including us!).

Lastly, I think one other issue is very important that HR alludes to in his quote above. And that issue is not just the limit of detection, but the reliability/trustworthiness of the result. As we've discussed before, having confidence in the technician/facility drawing and handling our blood sample is as important as the quality of the processed sample at the lab itself. It's important to get the best quality possible through and through, so we can have the highest confidence in our results. Therefore, I think what HR says above is really important. The lab he references sounds like a very reliable lab that's being held to the very highest quality control standards. That sounds like a place where someone like me and you should get our bloodwork sent (taken outside of the study of course). By combining the most sensitive test available along with the most reputable lab available would be the very best way to have maximal confidence in the final "yeah or nay" concerning our HCV infection status...*especially* prior to EOT. I also think finding a reputable clinic with very competent/experienced phlebotomists is equally important. Unfortunately, I don't know who would be best for that job.

Talk to you soon, try not and worry. We're all going to make it!