question for HR, results on two vial PCR

[cruelworld]

i did a two vial test.
one quantitative and one qualitative down to less than  2
i did the quantitative just in case it was high i would know how high.
they both came back UND.  woooo hoooooo

these are my questions:
1.  when the "less than 2 test"  comes back und, does that mean
that they could have found one viron or two virons or does it mean that they found none?

2. based on the pubished results (which includes room for error and liability)
this result should  guaranteed me a vl of  1.0 iu.  is this right?

3. based on what i understood about the true accuracy of the tests (no room for error and not legally guaranteed)  my results should mean a vl of 0.2 iu. is this correct?

other than that my thyroid is finally getting hammered at week 56  tsh  8.5. not too bad though.
doc put me on synthoid or whatever its called.
also hemo still slowly dropping and down to 9.6. still livable and no rescue yet.
more fatigued than ever but still tolerable and hangin tough.
my plan is to officially declare eot at week 66 and get a 10 vial test then. after that,
i will taper off for 6 weeks bringing me to a total of 72. this will give me a chance
to alter dosage in case the 10 vial vl comes back high.

[geterdone]

Well, the final shot was supposed to be the first Friday of February but it looks like it may to stretch it out by a week or so depending when I get my meds, hopefully next week because they have to be delivered this time, bummer. Yup! The best laid plans of mice and men, and I blew it on the 4 yard line and screwed up big time. I was with BCBS but the plan had changed over to Aetna Insurance January first and after all the horror stories that has been said here on the board about insurances companies.  I should have checked with GI guy about the new insurance and if there was any new preauthorization needed to continue treatment, which I did on Wednesday, the day I tried to get my prescriptions refilled. I really did not think about it prior to that because in my naive way of thinking I thought it would automatically transfer over to the new insurance because I’ve never have been on any long term treatment plan during one of these change over, duh!

Well as it stands now I should have taken the shot last night but Peggy failed to show up because I failed to get the bus ticket, so I am in the negative at the moment and will be for the next couple of days to a week. But, in any event I had 3 weeks left if I had taken the shot last night before starting the tapering down so it may wind up being a total of 54 weeks before the end and the end game still remains the same.

There is some thought as to the length of time in between shots and if it may be a negative factor this close to the end. In one way I would think not but in the other I just don’t know because of the laps time.

The link below will show my EOT plan.

http://www.medhelp.org/posts/show/393732?post_id=post_2325287

jasper

[ladywhy]

You're making me eyes well up again. Once listening to you and your horn  and now the cheering. I can hear it.
Thank you.
y

[cruelworld]

any diversion is welcome, glad you jumped in!
what is your plan for final countdown and when does it start?

[geterdone]

Cruel, apologize for high jacking your thread with these question for the fog has lifted somewhat before the next front moves in, lol!

jasper

[geterdone]

so I guess what I’m getting at with all this is what would be the “chemical” make up, more or less of this or that of the floaters at the top, as apposed to that of the many at the slower centrifugal speeds at the bottom?

Again Thanks!

jasper

[geterdone]

To possibly "identify" the ones with the thickest lipid coat?

Yes, because these virus cell have learned through the past encodings of previous generations of virions on how to adapt to its changing environment and use any means of survival including learned host dna of the virion strands through the replication cycle process over time in which more of the bodies defensive strategies are learned to combat the virus cell but the evasive maneuvers of the virus has figured out that the more lipid coating protecting it form the opposing forces of the bodies natural inf production and adapting to the treatment drugs over time has made it to what I call, a super virion.

It was interesting when St. George brought up the subject about statins and in the one abstract where (?statin name) was used that there was a VL drop but only temporarily but none the less there was a drop. My thought would be that the initial intake of the statins thinned the lipid coating of the virus cell in which the natural INF was able to penetrate the envelope and eradicate the process of the progression of the evolution of the virus. Just a wag on my part.

But if this did hold true and these virus cell had evolved to this state to where they defy the centrifugal forces of a centrifuge and these are the ones I would be looking at for the reasons of the margin of error and possible the reason for relapse because of the opposing external forces are no longer there and the virus cell by its own internal mechanism would start to shed it harden shell back to a point where the host liver cell becomes attractive again. Also another wag on my part, I think?

jasper

[geterdone]

O' forgot Synthoid, how sweet it is.

jasper

[geterdone]

I understand your concept for the eot vial test which would make sense to me “to know where your at before tapering down” and in the event that an anomaly may or may not occur and having the time to readjust accordingly, a way out in front of the curve thinking for ones own peace of mind before concluding treatment. I also see the re-injection point that jim is making about early in treatment testing for the population of Slow or Non Responders as covered by other threads as to the step down evaluation process of the various blood test and being able to readjust the meds early on at those varying points. But the fact of the matter is and as of this discussion is that You are the one going through these steps in REAL time and sharing the obtained information with us for which I am sure you have documented very well as we/us or whoever floats through the depths of the hepc abyss. Good Luck to you in your process.

jasper

[cruelworld]

thanks, i assume you are still riding the roller coaster. i hope you are making some headway.  have you made any changes to treatment?
how are your blood counts holding up? you are so close to
undetectable, you should be seeing it soon. im cheering for you
as loud as i can.

[ladywhy]

I'm glad to hear this news and glad it gave you a boost, and more confidence and strength to keep moving forward.
Sincerely,
y

[jmjm530]

The other point I forgot to make is that I think we may be quibbling over an uncommon scenario, assuming frequent TMAs during treatment. A scenario where late in treatment (or EOT) someone who has tested TMA negative (say monthly) all of a sudden becomes TMA positive -- and it should be noted that the EOT TMA positive studies did not test early-on in tx using TMA.

So, in a very practical sense, the real discussion as I see it is the usefulness of early, very sensitive and frequent viral load testing during treatment, which I think we both agree on. A discussion btw I just had with "Willing" and could have used your help, because his argument was that no study data except on the week 4, 12, 24 and 48 week test.

--Jim

[cruelworld]

ive always wondered why the "last ditch effort with all available weapons" concept is not used more often as a matter of course.
even without highly sensitive tests it only makes sense to try at least a few weeks worth of all possible weapons at the end of treatment. i have already asked my doc for a few months of infergen earlier and he said no. i will hit him for two weeks worth as  i get to the end. some might think this is overkill but to me
relapse is the ultimate overkill. in this blind game, it seems you should try everything you can think of - before relapse.

[jmjm530]

As a footnote -- I'm convinced that just about anyone can be cured of HCV given enough drugs for a long enough period of time. The point is at what cost? Risks versus rewards again. There's probably a very good reason the longest trials appear to be 72 weeks. Why no trials for 2, 3 or 4 years on full dose meds? It's because of the risks of the treatment drugs. The trend, thankfully, is toward shorter tx drug exposure, not longer.

[jmjm530]

I'm not saying that low VL (or ultra low VL) during treatment, should not ring alarm bells. In fact, I've argued the opposite (as you appear to be) that frequent and sensitive VL testing offers the enlightened and progressive clinician an opportunity to "tweak" beyond SOC and so to speak potentially pull SVR's out of the brink of relapse.

My point to "Cruel" (or anyone else on tx)  that these tests *are* useful, I'm simply questioning their utility at EOT as opposed to earlier in treatment. Cruel is stating that he wants to test at week 66 -- so let's say he is positive via ten vials? How long do you suggest he keep on treating -- another 24 weeks (90 weeks total)? More perhaps? That's an awful lot of meds with still no guarantee regardless of liver damage -- esp with newer, different acting drugs already showing results. And what about those with little or no liver damage who decide to treat -- how long is a reasonable length of exposure to these drugs for them?
------------------------------------

HR: In your particular case, if you has a pos ultralow VL test close to EOT and Dr. J or Dr. A or Dr. S or Dr. D would have said " you know, unless you want to wait for the future time of HCV antivirals, NOW might be by far the best moment to clear out these pesty remnants with all we have left in our arsenal" what would your answer have been?
------------------------------
Unlike most here -- especially back then -- my doc tested my VL monthly down to 5 IU/ml and I was always UND. Had I tested positive during tx -- sensitive or ultra sensitive tests -- and given that I had to assume around stage 3 damage -- I probably would have given myself an outside limit of 72 weeks total (I ended up with 54 weeks), assuming the doctors convinced me that going to 72 might be of benefit. Beyond 72 weeks -- or if I wasn't convinced 72 weeks wouldn't give me a decent chance given the hypothetical breakthough -- I'd have stopped. I was very beat up physically at 54 weeks. Don't know how I would have been at 72 weeks. Beyond that I'm not sure what would be left. As it is, treatment aged me at least ten years.

[Hepatitis Researcher]

By differentially spinning the virions containing samples one could indeed separate them by their varying density due to the variability in the lipid coating. Why would we do this, however? To possibly "identify" the ones with the thickest lipid coat?


Obviously the ultracentrifuge uses the highest possible speed and additionally means to reduce the buoyancy of the suspension medium to get the vast majority down.
By the way, once the density of a particular virion is less than the suspending medium, no centrifugal speed in the world will bring them down. They will go to the top, in fact.

[jmjm530]

If you're talking about the gap between the quant and qual (the two tests that make up HCV  N G I  quantasure quantitative, PCR LC#140639) then I believe it's quite a bit larger than 8 IU/ml (2 to 10 iu/ml). You can check this for yourself by looking up the range of the two tests involved. As to Heptimax, as I understand it, there is no gap down to 5 IU/ml, because no qualitative test is used. Quest uses two different quants -- a real time PCR (sensitivity 50 IU/ml) and a TMA quant (sensitivity 5 IU/ml). If for some reason you wanted to know a theoretical number that falls into the 140639 "gap" (not sure how useful that would be) you could have draw an xtra vial l (hey what's 11 vials when you're doing 10 LOL) and do a Heptimax as well.

[Hepatitis Researcher]

Unless the remnant strain/stragglers that are found at an ultrasensitive testing towards the EOT are already immune controlled, crippled remanants, unable to replicate up to high numbers once the extra antiviral pressure is of,  finding HCV at this moment would mean, that without some extra measure, that patient will relapse.

If you assume that to be the case, the next question is, if there is anything extra that can be done to possibly reduce/eliminate these stragglers.

Well, whatever the nature of these stragglers, they are at a very very low number at this point.  If you assume that nothing is available to eliminate them, that they are not responding to say Infergen, extra ribavirin, Alinia, prolonged pressure (extending using SOC meds), Double dosing, Lactoferrin, Thymosin Alpha,  then

that superresistant pack

will only get higher in number after you let go of treatment and retreating after you let them grow back to full strength would have even less a chance to go to SVR, since by your operational definition, they will not respond to any of the "reserve"measures that are currently available.
So why retreat later?

In reality, in some cases, we dont know in % which of course, no studies, those extra means will eliminate the stragglers, leading to SVR, because you activated all the reserves, when the enemy is at his weakest.
Infergen, for example is known to activate other Interferon receptors and therefore allow some regular IFN resistant HCV to be eliminated. Why would that not be most effective at the time of an ultralow VL?

When you refer to the individually treating ( beyond SOC) top hepatologist that patients should see , you must have some treatment variations in mind that go beyond SOC. Why would those intensifying means not be particularly effective at this point in time, against an ultra loow VL? At least in a good percentage of patients? Whe retreat them later at much worse odds?
One could say of course they should not retreat anyway, but wait for Vertex or other HCV antivirals to become available first. True for many, but some might not have the time and need to try the best they can. In these cases why would it not be the best moment to hit the minute amount of stragglers once you know you do have them in your blood, while they are still ultralow and cannot develop additional adaptive mutations due to their ultralow numvbers?

St.George is now starting his torturous Infergen+++ treatment, after his Vl has gone up to higher numbers. Would he not have had a better chance to use the same treatment at the moment before EOT in the ultralow condition?  If he had only known then , that he would relapse at this moment?

This strategy is certainly not practicable for the majority, for several reasons, aas we are all aware.
In your particular case, if you has a pos ultralow VL test close to EOT and Dr. J or Dr. A or Dr. S or Dr. D would have said " you know, unless you want to wait for the future time of HCV antivirals, NOW might be by far the best moment to clear out these pesty remnants with all we have left in our arsenal" what would your answer have been?

[geterdone]

I would like to Thank You for your input and in answering my question as to some of the mechanics of the virus which I know is only the tip of the iceberg and way over my head but thanks for your time and feed back.

jasper

[cruelworld]

jim
as i tried to say earlier, any alteration of treatment based on vl info
near the eot would be a small time extension and or a 50%
overdose. nothing drastic. only a last ditch effort.  the bulk of the treatment is done.  i definitely agree that ones fate is mostly already sealed at this stage.
i will call lab corps monday and try to get info about the statistical occurrence of samples that fall within the 2 to 10 iu range. i will also call quest to ask the same question for 5 to 10 iu. if i can get the info i expect those results to be rare but i could be wrong.

geter
glad you reminded me about that. since i will still be taking
inf, i will probably do all 10 vials at once at the end of the 7 day cycle one hour before the next shot. thats what i did this time around.
this will give me results at the lowest inf concentration.

[geterdone]

Ha! I wrote this and posted it two days ago, and thank you again.

jasper

It is not so much as the liver protecting it self as it is with the “virus cell” floating around and hitching a ride on the plaque in the veins and in some instances being coated additionally by the tumbling lipids and sticking to the plaque and eventually being encapsulated in it over time which brings me back to the virus cell and the thickness of the cell envelopes which is not soluble and floats at various degrees with in the blood stream in which the cells act as balloons because of the chemical make up of the inner membrane and outer coating and the varying buoyancy of each cell given that make up and coating.

Hope HR is lurking because I doubt if I’ll remember this scenario, in which all probability is totally wrong but here goes.

Using hr’s example of the ten vials of 1ml of infected blood serum all from the same draw and using ten centrifugal mixers (lack of better word) and set at different speeds among the ten vials what would be the viral content at the various speeds and the viral buoyancy of the virus cell at each speed. Now if going by the different centrifugal speeds and all ten vials show different concentration of virus cells and virion at those different levels what would cause those virus cells and virions to stay buoyant at that given speed, and of that, what would be the thickness of the envelopes in each virus group? In looking at it this way the newly created virus cells and virions would be lighter and would sink to the bottom at the slower speed because they have not had the time to mature and flow through the blood stream and pick up additional protein coatings of its outer cell envelope and in contrast; the maximum centrifugal speed would yield the most hardy of the virus cells and virions because of the length of time floating in the blood system (years) and picking up the additional proteins of insoluble coatings of the outer envelope along the way in which it makes them more buoyant in our water based blood system and would it not make more sense that the newer virus cells and virions get eradicated faster in the beginning of treatment because of this lack of additional protection of each? Sounds far out but to the layman sounds logical for a hepc 101 class minus all the sifi wording.

So, say out of the ten vials centrifuged, vial one has 500k virus cells and virions at the lowest rpm and viral 10 has 5000 of the virus cells and virions at the maximum rpm would it be safe to say that what in the virus cell has made it so resistant to the downward pressure of the spinning centrifuge.

[Hepatitis Researcher]

The "floaters' are explained by the lipids that the virus attracts to its outer , partially lipohilic virion coat sections, that make it possible for HCV to protect itself from neutralization by antibodies. This coating is variable for two reasons:
1. Because of the quasispecies/genetic variability of the individual virions, some might have an even better ability than the majority to bind those extra lipids.
2. Due to the stochastic process that underlies the lipoid coating there is some variability - a "distribution" - of lipid coating even with genetically identivcal virions.

The ultracentrifugation steps tries to oversome the floaters by reducing the specific gravity of the serum in which the virions are suspended at the time of centrifugation, thus making them heavier relative to the medium in which they are centrifuged, sending them to the bottom after almost 3 hours of ultracentrifugation.

[geterdone]

I see your point and your eot goes without saying as to the tapering down for which I will also be following giving hr’s recent comments on the subject but I am still confused and mystified about these “floaters” hr keeps referring to when these NGI test are brought up and why they do not sub come to the centrifugal pressure and what would be the properties that will not allow them to be pushed to the bottom. Question tho, these ten vial test your planning at week 66 will it be from one draw or spread out over a week or so?

jasper

[jmjm530]

I previously wrote: For one thing, you'd have to drain your body of blood for certainty -- and because of the multiply/kill process, you would probably have to draw 10 vials hourly, for 24 hours, to conclude you have no virons in your serum -
------------
Actually, you'd have to drain your body (test all your blood) hourly for such a conclusion, as some errant virons might have survived the interferon in serum.

[jmjm530]

BTW I'm not really suggesting that you do 10 vial tests monthy throughout treatment, just trying to add to the discussion as to what value you might (or might not) get with an EOT 10 vial test.