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)

[FlGuy]

If you don't mind, I'd like to add a Part B to your question. It's related and has been on my mind.   If the intent is to get a pcr after tx ends and the meds have been discontinued, when is the best time to get such a sensitive pcr if the intent is to catch relapse as soon as possible.  Is the answer 1 week, 2 weeks - a monht?

[jmjm530]

PDS,

Let me make it simple first. If you want to privately get a readily available and sensitive test, either of the following will do just fine. Both have a sensitivity of 5 IU/ml.  My preference would be #2, mainly because that particular test is run exclusively at Quest's Nichols Institute at Cupertino, California, regardless of where the blood is drawn.

(1) Quest Diagnostic's "Heptimax".  

(2) Quest Diagnostic's "HCV RNA Qualitative TMA".

-----------------------
Less simple -- the test you've already taken should do equally as well if they will administer it right away, which is what you probably (and should) want. From what I understand, your "29" means you were detectible somewhere between 10 IU/ml and 30 IU/ml. But if it were me, at this point, why not go to another lab just for peace of mind (and clarity). Therefore one of the two tests I mentioned will do the trick.

-------------------------------

FlGuy,

If the intent is to catch relapse "as soon as possible", then you would want to test EOT and weekly thereafter, at least until week 4 or 6 -- as most relapses appear to occur within the first month after stopping the treatment drugs. If it's a case of judiciously spending your money, then I'd say test at weeks 2 and 4 as a compromise but I have nothing scientific to back it up. In any event, you would want the most sensitive test possible, such as one of the two tests I mentioned above to PDS. Some also test a couple of weeks before EOT, so in case of a positive they can continue on with the drugs if that is part of their strategy. In my case, I tested at weeks 2 and 6 -- the week 2 test was because I was getting antsy and week 6 because a negative 4 week post tx test is heavily associated with SVR, even more so I assumed at week 6. I had no plans to jump back into treatment however, regardless of results, so my concerns were different than yours.

All the best,

-- Jim

[neptune235]

Unless I'm mistaken, Qualitative tests are generally more sensitive than quantitative tests.

The TMA test is a qualitative test, and the level of detection is < 5 IU/ml.

I think ideally, one would want to run both an ultrasensitive qualitative test, and a quatitative test.  So...a good result would be UND from the qual, and 0 (or less than the detection limit) from the quant tests.

I missed the quoted thread by HR, but it sounds to me like he is talking about running a test at a certain specific lab that has a protocol that yields a very low contamination threshold.

Contamination is one way a false positive could be created.

[jmjm530]

Actually, some of today's quantitative tests are as sensitive as the qualitative tests. For example, Heptimax is a quantiative test (using tma technology) and is sensitive down to 5 IU/ml. As to running both a quant and a qual from the same blood draw, many would think that a bit belt and suspenders and possibly neurotic. That said, this is exactly what I did for my three month post treatment test. I ran both of the tests simultaneously I mentioned to PDS above. Of course, had one come out positive and one negative, I would have been in confusion h*ll :) Fortunatly, both came out non-detectible to the limits of the respective tests which was 5 IU/ml.

All the best,

-- Jim

[prettydamscared]

Good point and I now have another question too.  Is there any particular reason why people talk about getting a TMA at EOT.  Is it just because it's one of the most sensitive tests around and a good indicator of possible svr?

[prettydamscared]

Thank you both for your responses.  You did both make it simple which I appreicate and I now know how to proceed.

Charlotte

[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!

[Kalio1]

Im not sure how important the sensitivity of the test being matters be it down to 2, or 10 or 50. If you relapse, the most common way is to have the virus come back quickly and in plenty of numbers to be detectable by any of those tests. If it's back, it's back and that will be obvious. Some do relapse after the first few weeks or months and some just have a ssmidge of virus show up at first when they relapse but the majority would be detectible by most measures is what I was told.
I'd  time my EOT PCR test at 2 weeks past last shot and then at least another test at 12 weeks and again at 24 weeks. If you can get the doc to do it, I't try to get them weekly like Jm suggests if you plan on continuing therapy.

[prettydamscared]

HR's post to MissMiss:

"9 month after SVr you need to use Labcorps NGI Ultraqual LC#140609. Nothing else and as sensitive as Heptimax. I have discussed prev. why NGis contamination issues are dramatically less than other labs and the whole facility is FDA certified. Since every contamination could destroy 512 plasmadonations and yet 1 slightly positive diluted in a pool of 511 negs MUST BE DETECTED, you can imagine the extremes which had to be established there."

I'm assuming there's no particular reason for HR to have suggested this test to use 9 months after svr other than the fact that MissMiss was going for her 9 month pcr.  Should I use the one suggested above by HR or is this a QUALITATIVE test?  Have to admit, I'm confused easily these days and don't have the energy to thoroughly research this.  I'm not even sure how important it is, i.e., is one drastically different from another.  I'm just confused over the 29 issue and no amount of explanation from my doctor fully allayed my concerns so just want to be sure I'm undedected at this point. (22 WEEKS) I would prefer to use LabCorp if possible because that's who my GP deals with and it would be easier.

Thanks in advance for any help.

Char

[mremeet]

Oh, one other thing I'm curious about re the often touted TMA - are low level qualitative tests more reliable than low level PCR quantitative tests? If low level qualitative tests have a higher margin of reliability/confidence, that might also be a reason why it's referenced so much as the apparent gold standard of HCV +/- referees.

Also char here's a couple of Labcorp sites you might find interesting:

Here's the test I used: (quant down to 2 IU/Ml)

http://www.labcorp.com/datasets/labcorp/html/chapter/mono/id004600.htm

And here's an ultraqual: (qual down to 2 IU/ml)

http://www.labcorp.com/datasets/labcorp/html/chapter/mono/id003400.htm

[jmjm530]

Actually, it's the higher level tests that have the most reliability as I understand it and therefore one reason Bdna's with a sensitivity of 615 IU/ml are often run first, alongside, or are automatically reflexed to the more sensitive tests -- to keep them honest so to speak. For example, if you were TMA negative but Bdna Positive, I wouldn't start popping the corks right away. One of the things I liked about Heptimax is that it runs a quant real-time PCR first which supposedly is extremely reliable. Only if the PCR is negative do they run the quantitative TMA. So, at least you're more or less assured you're non-detecible (or detectible) to at least 50 IU/ml which is the limit of the PCR part. By adding a qual tma to my own mix I was just keeping the quant tma honest but probably not necessary.

[Hepatitis Researcher]

When you strongly suspect to be negative by an ultrasensitive test then  you run a qual test like HCV NGIs Ultralqual ( Labcorp#140609) This will show you negative if you are below 2 international units.

If you think you are very low but not ultralow, then you order HCV NGI Quantasure ( LC#140639) that will give you a number from 2 iu to 2000000 iu. or not detectable below 2 iu.

Its a combo quant qual test. Max sensitivity combined with quantitation.

Why not always use the second one? Its more work and therefore more expensive.

[Imagine]

I guess my question would be is how many does it take to tango/replicate? The international unit is still a little confusing to me. If two people of the same genotype, same age, same stage, both are undetected at wk4 using the same pcr testing methods and remain so through 48wks, why then would one achieve SVR and the other relapse?

I am not sure if there is an answer but sure would welcome possibilities. It is something I really wonder about since I have relapsed. I know the why will not help me but it sure would satisfy my curiosity. Could it be the particular strain of say 1a that these two people had that makes the difference?

[motheroffour]

Will Quest labs automatically run the Heptimax?  My H has his bloodwork done at the local hospital but several blocks away is a Quest lab.  His doc doesn't care where he gets his bloodwork done.  The hospital runs a test that says  Mayo Clinic UND <615 but doesn't give you any more specific information.  He was UND <615 at 12 weeks.  If you go to a Quest lab do you have to request a specific test or is doc's lab slip with PCR checked enough info for them?  I'm very confused about these labs.  The docs says UND is UND and that's what the research proves out, but we can have whatever test we want as far as he's concerned a PCR is a PCR.  My insurance company says the same thing. Have there been studies that show a statistical correlation between UND <615 testers having a higher percentage of relapsers than UND< 5 or some other group tested to the lower numbers?  H's doc says "no" but if I can find one he would be interested in reading it.  He does appear to attend symposiums and attempt to stay on top of new trends and we're happy with him considering we live in a small town.  He's open to conversation and we've had several regarding "what" UND really is.  I'm the one that worries that H will be a relapser because of his liver bx (probable cirrohsis)

[motheroffour]

Thanks for the info.  I'm going to look for that Chicago paper.  An old beau of mine is a former NIH/Johns Hopkins HIV/HCV co-infectious disease specialist and I was sorely tempted to make contact after 20+ years to get some definitive answer to this testing question as it seems to be a sticking point with many of the mainstream docs.  I made a similar argument with the doc based on what I've learned here.  I'm considered an intelligent person ('though not a medicine "doc") and the doc conceded that the rationale/argument was sound, but felt simply that there was no substantive information to worry about searching for a more sensitive test. He simply deferred to whatever I felt "we" should do.   I'll add Heptimax to my H's lab and have him go to Quest lab (doc gave me his entire year's worth of lab slips and just calls me and tells me what he wants to run so the reality is I can write/X anything I want).  I'll sleep alot better if I feel that UND really is UND, right now I'm not convinced but I don't say a word to my H as he's feeling on top of the world (which in some respects he is at 13,000 ft. w/skis strapped to his feet right now).  I am continually impressed by the depth of knowledge and conversation on this forum.  I'm grateful to have stumbled on it.  I'm also cheered by the fact that our family doc grills me every four months when I'm in to see him about this disease.  I think he's feeling a tad guilty for not discovering this in my husband when his liver enzymes rose in 1988 and rose again in 1998.  If only I knew then what I know now...  sigh.....hopefully the family doc will be a smarter family doc.

[Sincebirth]

I have read this thread and will try to explain the kenetics of the viral decay and how it will relate to the PCR testing and sensitivities.  Then hopefully somebody like hepatitisresearcher can chime in and tell me if this is right.

It seems that there are 2 main slopes to viral reduction which are the following:

1-Initial quick drop in the first 24 hours of TX, this is due mostly to the initial kill of the virus directly and is due to the interferon mostly.  Usually a 1 to 1.5 log reduction.

2-The next stage of viral reduction is usually represented by a logrithmic decay of the viral load and is typically linear along the log graph.  This slope along with how long you treat will ultimately determine your chances of success.  I think the slope of this line is due to your body's ability to kill the infected hypocrites (sp) and this can range from individual to individual.

Now to the good stuff:

To get a sustain response you need to drop you viral count to nearly zero.  NOT YOUR BLOOD tests which only measure a mere fraction of the the amount of plasma in your body, but you whole body.

The amount of virus detected in your PCR represents a small fraction (1/10,000) of the viral copies in your total body. So say you have 9 copies (which is undetectable with a very sensitive test) you could have approx. 9 X 10,000 or 90,000 copies of virus in your system. That 90,000 needs to get pretty close to zero to get a sustained response. You need another 4 to 5 log drop of viral load to be clear.

So hypothetically speaking, the sensitivity of a PCR test to actually tell you if you are clear of the virus would in theory be 0.00001 IU/ml.  

So when we speak of a test that goes to 5, 10, 30, or even 50, all these tests are relatively the same number because they are within one log of each other.  

So to recap, somebody with a starting viral load of 1,000,000 would need an 11 log reduction to clear the virus.  A (10 iu/ml)test would only measure a 5 log reduction, And a (50 iu/ml) test would only measure approx. a 4.75 log reduction.  On a log scale these numbers are virtually the same.

Any thoughts?

I am also going 72 weeks.

[mremeet]

If your doctor is receptive to discussing the possible benefit of testing at the lowest level possible, then I'd simply print out the studies referenced above by PDS and HR and then hand them to your doctor on your next visit. Use a highlighter to mark off the most salient statements, including:

"Among patients treated with combination therapy for chronic hepatitis C, the TMA (5-10 IU/ml) test detects HCV RNA in all specimens that are Amplicor-positive (50-100 IU/ml), 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."

The benefit of a more sensitive test as described in this study seems pretty straightforward and common sensical. Hopefully your doctor will agree. And if he does you'll not only be helping yourself, but you'll be helping his future (and current) patients by bringing it to his attention as well. But even if he doesn't see the light, sounds like he won't object to you getting the more sensitive test anyway.

[motheroffour]

Agreed mrmreet.  I guess somewhere deep inside of me I just want to be right and "win" this one with the doc (and for my H's future well being)  so I'm looking for intelligent support for my argument! I'd pretty much convinced myself I was right and was thinking I'd write up the lab slip as such.  The tenatious pig headed part of me wants the "young whipper snapper doc" to concede and he just won't bite!

[mremeet]

He may not admit that you're right to your face, doctors have pride and ego like anyone else. But inside he'll know you're right, and much more importantly he'll probably incorporate what he learned from you into his future practice - hopefully for the benefit of all his patients.

[Hepatitis Researcher]

First ; TMA = Transcription Mediated Amplification, an in vitro amplification method of small stretches of RNA that uses RNA Transcription rounds for its amplification cycles.

  PCR = Polymerase chain reaction. It uses up to 55 rounds ( cycles) of a molecular biology reaction that starts with a small specific  stretch of DNA e.g. 100 bases long that are part of the viral genome and duplicates that starting material in each round again and again so that in the end a relatively gigantic amount of that specific stretch the " amplicon" is made, still "proportional" to the starting amount, so by quantitating the end product so can quantitate the starting amount = the virus by comparison with a standard that you have equally amplified.
With HCV , a RNA virus, the RNA is first reverse transcribed into DNA, then PCR is used.

A qualitative  test is nothing more than a TMA or PCR where:
1. a much larger amount of serum (starting material to investigate) is being prepared and
2. then the amplification process is driven to the extreme, to detect any copy of a virus present in the starting material. This way you obtain highest sensitivity, but you loose quantitation above the detection limit, because you literally "overamplify". Often even a single copy of the virus in the starting material of 1ml of serum will be detected.
Everything has to be optimized to achieve this result. This is called " Robust single copy PCR".
Sometimes HCV is so intensely lipidated, that the ultracentrifugation step used to pellet it down from the starting serum, despite lowering specific gravity of the serum,cannot cath this virion - it floats, because it contains too much fat. Thats why the sensitivity limit is "officially" 2 iU = 5 copies(virions)/ml.



In quantitative PCR we simply use much less starting material and less and less cycles to obtain amplification strength that allows quantitation in the desired range.

[Imagine]

Sorry, I probably should have opened another thread for my question but since the discussion was about PCR testing I squeaked in here.

[Hepatitis Researcher]

"The docs says UND is UND and that's what the research proves out, but we can have whatever test we want as far as he's concerned a PCR is a PCR. My insurance company says the same thing".

So like <600 iu has about the same meaning as < 2 iu ????

UND is UND ???

Obviously very, very wrong. It is nice to know that you have at least 300 times less virus in your blood when you are "UND" with the more sensitive test then with the crude test.

As I had posted before... ; A study presented at the Chicago AASLD (abstract # 2442 late breaker) conference comparing the predictive power of the then 400copy cutoff Amplicor with the 5 copy cutoff NGI test at week 4 gave 45% versus 92 % predictive power for later SVR..

Even with the very best test, if neg or non detected : It does not mean you do not have virus in your blood still circulating!It just means - with the very best test - that the one little Milliliter that we have tested did not contain more than 5 virions ( or 1). But you have 5000ml of plasma and much more interstitial fluid that still possibly contains virus.

If a patient has such a rapid decline that he is UND with a supersensitive test at week 4 then this means that the slope of the decline is steep and we EXTRAPOLATE from here on that by continuing treatment in the same fashion for 24 or 48 weeks, that the virus will further and further and further decline NOW ALL INVISIBLE AND UNTESTABLE but still real and deciding SVR or not.

If we had no more virus in the body once "UND" we could stop treatment right then.

[jmjm530]

Quest probably has close to a dozen different tests for Hep C. Have no idea what test you might get if your doc simply checks "PCR". Not a great idea. However, if the word "HEPTIMAX" appears on the rx or requistion form, then there will be no confusion. There is only one Heptimax test.

Hope it all works out.

-- Jim

[Hepatitis Researcher]

Your above comment is mostly a good description of the viral kinetics. When it comes to the levels below UND we are somewhat in unknown territory.




""""
1-Initial quick drop in the first 24 hours of TX, this is due mostly to the initial kill of the virus directly and is due to the interferon mostly. Usually a 1 to 1.5 log reduction.""""

If you had a means to stop the production of new virus entirely you would get in the logarithmic y / linear x-time scale plot a straight line down to zero. Existing virus in the blood has a half life of 4 to 6 hours. So until de nove production becomes relevant again ( at a lower level) you are mainly seeing the exponential decay curve simply by removal of circulating virus ( this is not killing by interferon, simply removal as usual, as you had it before treatment). The de novo blockage at this level  reflects the "direct antiviral effect of IFN", combined with intensified cytokine responses by the resident immune cells, thats mainly NK,Tcells and dendritic cells.

Once you have dropped to a level whereby the virus is still replenished by de novo production, the slope will turn to a more flat second line which is indeed reflecting the further reduction of viral production by eliminating infected hepatocytes.




""""
2-The next stage of viral reduction is usually represented by a logrithmic decay of the viral load and is typically ALSO linear along the log graph. This slope along with how long you treat will ultimately determine your chances of success. I think the slope of this line is due to your body's ability to kill the infected hypocrites (sp) and this can range from individual to individual.""""

Yes this second process will probably determine the ultimate outcome in each particular patient. What we do not know is if this process indeed proceeds to Zero or stops at a smaller amount of infected hepatozytes that have inside virus that has escaped by virue of epitope mutation or cytokine blocking mechanisms, but the memory cells remaining in the liver provide enough long term local "antiviral milieu" to block a new rise of the infected remnant population.



"""To get a sustain response you need to drop you viral count to nearly zero. NOT YOUR BLOOD tests which only measure a mere fraction of the the amount of plasma in your body, but you whole body."""

That is one - the "older" theory. With several studies finding remnant virus in SVR livers it might be more as i outlined abvove.  

""""The amount of virus detected in your PCR represents a small fraction (1/10,000) of the viral copies in your total body. So say you have 9 copies (which is undetectable with a very sensitive test) you could have approx. 9 X 10,000 or 90,000 copies of virus in your system. That 90,000 needs to get pretty close to zero  WE DO NOT KNOW HOW LOW IT HAS TO GOT   to get a sustained response. You need another 4 to 5 log drop of viral load to be clear.

So hypothetically speaking, the sensitivity of a PCR test to actually tell you if you are clear of the virus would in theory be 0.00001 IU/ml.

So when we speak of a test that goes to 5, 10, 30, or even 50, all these tests are relatively the same number because they are within one log of each other.""""



IF YOU LOOK AT THE 4 COPY AND 400 COPY UND DIFFERENCE YOU HAVE A TWO LOG DIFFERENCE. That is enough of a difference to gauge the different  steepness of the initial decline to allow meaningful extrapolation.

"""So to recap, somebody with a starting viral load of 1,000,000 would need an 11 log reduction to clear the virus. A (10 iu/ml)test would only measure a 5 log reduction, And a (50 iu/ml) test would only measure approx. a 4.75 log reduction. On a log scale these numbers are virtually the same. ""

I agree that the difference between 10 and 50 on the overall log scale becomes almost irrelevant. but between 615 and 2 the log difference and the reflection of the reductive power of the treatment is real and can be estimated with good predictive power.

[jmjm530]

Yes, by all means make your arguments, but the bottom line is to make sure "Heptimax" is written on your husband's lab sheets so he will get one of the most sensitive tests available.

[FlGuy]

The comments made by sincebirth and HR has been my general understanding which I’ll paraphrase (maybe inaccurately) as nuke ‘en, watch them die a natural death and for the ones remaining, disable the ability to reproduce.  The slopes make sense to me and the ones that can’t be counted are the ones that are the issue.  Now I’m wondering if the approach I’m using this tx will address all the aspects of complete viral elimination.  Having double-dosed Peg the first 4 weeks and pre-dosing riba for one week before first injection, I got to und at week two.  After week 4, I’ve been on SOC  180peg/1200 riba.  So, now I wonder if the aggressive approach taken in the early weeks of tx have any bearing on the continuing need to limit replication.  I realize that by eliminating many fast that there are fewer to cause replication (fewer parents, fewer offspring sort of). Have I achieved only shock and awe, or really have done something early on that will be worthwhile to the longer fight, the ones that can’t be counted?