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Measurement of VL in first 12 wks of treatment
by Trish77, Feb 02, 2008 09:48AM
I would like to know how important it is to all of you to know your exact VL during treatment at 4 and 8 weeks. If you have a PCR that measures down to <50IU/ml, are you content with a Pass/Fail until that week 12?
This is the scenario I'm in for and I'm not happy about it, I want to know my exact VL count at 4 weeks and 8 weeks if I fail, as in I'm above <50IU/ml. Is this reasonable or am I getting uptight for nothing? I'm thinking if I know at 4 weeks that I'm not doing so well, I can ask the doctor to alter my treatment to increase my odds. Then I can measure again at 8 weeks how it's going. A pass/fail doesn't give me enough information, I'm thinking. Am I off-base there? Hard to know if I'm letting emotions get in the way of clear thinking at the moment.
(I posted all my questions in one post on the other side..but way too much to slog through I'm thinking so I'm breaking it out individual posts for the questions that are on my mind.)
This is the scenario I'm in for and I'm not happy about it, I want to know my exact VL count at 4 weeks and 8 weeks if I fail, as in I'm above <50IU/ml. Is this reasonable or am I getting uptight for nothing? I'm thinking if I know at 4 weeks that I'm not doing so well, I can ask the doctor to alter my treatment to increase my odds. Then I can measure again at 8 weeks how it's going. A pass/fail doesn't give me enough information, I'm thinking. Am I off-base there? Hard to know if I'm letting emotions get in the way of clear thinking at the moment.
(I posted all my questions in one post on the other side..but way too much to slog through I'm thinking so I'm breaking it out individual posts for the questions that are on my mind.)
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-- Jim
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No, in general, you are not off base, however there are a number of things to factor in such as your genotype, prior tx history if any, the amount of liver damage you have, your race, weight, height, age, doses of riba and peg, pre-tx hemoglobin and hemoglobin response during tx, etc. You might want to include some of all of this in your profile.
-- Jim
As for drug trial, I'm treatment naive at the moment. I have big decisions to make the next while. I wish he would have told me which trial but he didn't want to. He was in a big rush and brushed off any question that wasn't relevant in HIS eyes. I'm frustrated with myself because if I'd controlled my emotions better, maybe I could have spoken up for myself better but it threw me off finding out I won't get to know my exact VL going in and his response to me pressing the issue on that. He was hungry, thirsty, abrupt...and I lost my grip on pressing for the info that was so important to me. Really, I was afraid he would tell me to find a different doctor. I did get alot of my questions answered by the NP...but in the end, I left without the copy of the blood test even....I really found it distressing to get the kind of answers I got....no exact measurement of my VL going into tx, no exact measurements until 12 weeks, no extension of treatment to 72 if I'm a slow responder.
I don't know, FlGuy...alot of emotions on this one and I'm trying to sift through to find clarity of thought without the distortion that emotion can bring to it.
I'm curious. What happens to people in the U.S. if someone wants a PCR at 4, 8 and 12 and to certain sensitivities? Is this at the mercy of your particular insurance company and also whether your doctor will do this?
It will be very interesting to see what sort of response I get if I ask for a PCR with lower sensitivity. The NP seemed to be saying I should be very pleased with the one they're using as it's a low sensitivity. Imagine if I come along and say I want an even better one at the 12 week mark. If it's covered under healthcare, there should be no issue. If it's not, then I will, in the meantime, be exploring what options are available to me.
Having said that...any idea what it costs to get this test done in the U.S.? I am not that far from the American border.
Thank you for your input, Jim.
Trish
I believe you have until 24 weeks to see how you respond, thats what I was advised.
Good luck-They didint want to give me the 8 week I had to beg and complain alot.
Charm27
We tend to assume that vl measures the actual amount of virus in the body, that when you geto und it's gone, or nearly so, and thus that it's important to make those measurements as accurate as possible. Unfortunately this view bears little resemblance to reality. Viruses are viruses because they cannot reproduce outside of cells, thus the amount of "free" virus circulating in blood is a very approximate indicator of the number of infected cells, and the copies of virus they contain. An analogy I posted a while back is that a vl measurement is like trying to estimate the population of a city by taking a snapshot photograph of a section of freeway.
Every relapse as well as all the publications on occult hcv underscore the discrepancy between vl and actual infection. However, measuring infected cells is hard/impossible, drawing blood is easy so we've go to work with the tools available. So what does a VL measuement tell you?
By itself, very little. We know VL does not correlate with liver damage and can bounce around 1-2 log units (10 to 100 fold) in a static, chronic infection. The principal value is that the decline in successive measurements, while there's still enough virus to observe in blood, indicates a trend. Comparison of one' vl decline with that collected for others allows one to gauge response to the meds and thereby estimate svr outcome.
If you don't have anything to compare against, the information from a vl test is of very limited value. For example, if you can find a study, any study, that found a significant effect in being UND<10 vs UND<50 at say week 4 or 8 then, and only then, would be reason to fret over missing that test. A key example is that there is now quite a bit of data showing that at w12, significantly different relapse rates were observed in 48week 1s that were UND<600, UND<50 and UND<10 so clearly that test has high predictive value.
If you can get frequent tests, by all means do so. As Jim likes to point out, even if the comparison data is not available now it may be in the future (though my obsevation has been that old test results seem to be of limited value). However if you can't get your Dr. to order tests that won't make any difference in his/her tx decisions (which essentially are stop/extend), it's not worth getting upset about. Possibly the worst consequence of infrequent testing is the failure to detect breakthrough, thus continuing a pointless tx, though even there the data is a bit sketchy.
Thanks again
Deb
The viral test that is the most sensitive here is the real time PCR, good to <50 and concidered as accurate as needed, eg, what percent is <50 of 1.3mil, do you really need to be more accurate than that?
Knowing where you stand at the begining is important, so you can look for that 2 LOG DROP, this is the most important number to look for. So you started at 1.3 mil, treatment will be concidered to be worth continuing if at 12 weeks your level drops to 130,000.
We need to find Doctors that we TRUST so we don't second guess them. Trust is earned by credentials, respect and explanations, weighed against what we can gather on our own. Your Doc and team is well respected out there so get them to explain their decissions. It will help to calm you and that will make treatment simpler to take and the less stress you have the better your chances are.Let us know what they say...please.
Good luck
Harry
I can think of plenty of reasons why they should treat us well right from the start, from both a health and healthcare cost perspective. If treatment fails, for example, we have to keep trying until it's successful. All of that costs money to the system and stress because there are only so many doctors to go around who specialize in HCV. It's also stress on the patient and disruption to their life. The treatment is not a walk in the park, right? So...to me...it makes perfect sense to do as much as possible to make the first go-around as successful as can be. As well, to treat earlier when you're in better shape seems to offer the best chance of success. If I'm able and willing to treat earlier, why not support that? When an HCV person chooses to treat, it's a carefully considered decision and they're doing it at the time that makes the most sense to them having considered many different variables. To me, that too ensures a better chance of success. I think it's short-sighted and counter-productive in so many ways to put up roadblocks for those of us in early stage liver damage from treating if we find we are of the capacity to do so.
As for my viral load....it's not 1.3mil, Harry. It's above that somewhere and I don't know where. That's simply the upper limit of the assay used. If they are only going to permit one, then they should use one with a much higher upper limit. You mention what my log drop should be... but suppose I'm actually sitting at 6mil IU/ml ? Then a successful two log drop could be interpreted as slow response if they're going to assume that the upper limit of 1.3mil IS my VL...which it isn't. It could be 1.4mil, it could be 10mil. We don't know. So that frustrates me. Incidentally, the NP told me I need a drop to 1000IU/ml to have a two log drop. So I dunno...I haven't done the actual calculation myself as I don't know how to calculate it just yet, but it's another item on my "must learn" list.
I hear you on the trust issue thing. I agree with you. And if the doctor will have the patience to answer my questions...and in turn, I understand why he would rather not answer some questions yet, as in none of the more detailed tx questions because I may end up in a drug trial...if I respect his time and education and he respects my need to understand.. I can relax and trust him. I agree with you. He should feel comfortable explaining his decisions. And then...I will be able to relax and trust him. I may not like the information I've gotten but at least I'll know the reality and work with that.
Thanks for your words, Harry. Appreciated.
Trish
In my opinion, the Why's have less to do with study data and more to do with the fact that most clinicians are a year or more behind the treatment curve. As to the "4" and "8" week example, above, it's not just future usefulness we're talking about. "Susie2007" has already mentioned that Dr. Sh has already stated that more frequent early testing can differentiate between and EVR and a null responder in certain scenations, providing valuable information to the clinician in regards to future PI treatments.
"In my opinion, the Why's have less to do with lack of specific study data and more...
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Zazza, I didn't do any math on what the NP said, I just noted it. So was relaying it. Seems Harry's math is better, eh? :) Thanks for the clarification.
a 2 log drop from 1,300,000 would be 13000
Pro
In some of these poor doc's defense...they probably never trained in medical school for having to deal with educated patients, and take offense to the show of knowledge...they probably go to bed every night cursing the internet (lol)...
oh well, enough rambling....trish I did find this link (you've probably already have it)...but basically outlines CA's soc for hep c
http://www.phac-aspc.gc.ca/hepc/pubs/mvh-pchv00/virus_e.html
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Since I believe you are pre-treatment, do you mean "exact" or "sensitive"? Yes, it could be "thousands or millions higher" due to test variance, but within the context of logs it's important to have a pre-treatment viral load done to computer log drops during treatment as well as for predictive value where low viral loads have predictive values -- higher viral loads less predictive. The more sensitive tests become important once treatment has started to confirm UND.
-- Jim
Moving forward, the week 4 test is fast becoming a standard part of treatment. Data back then was avaliable to suggest the importance of RVR but it just didn't get filtered/assimilated into the general physician population and/or they were awaiting for larger/more confiriming studies. BTW, about the doc, who told me that all I needed was a week 12 test -- I just read a published article he wrote about the importance of the week 4 test. While I agree we should try not to obsess about anything outside of our control, if available, asking for frequent and sensitive viral load tests has no downside, only an upside -- outside of the financial issue which insurance usually picks up if the doc writes a rx. The week 4 standard is one example. Studies about frequent viral load testing during tx to pick up relapses is another. And then there's Dr. Sh's conversation with Susie2007 about how the lack of frequent early vl testing leaves clinicians with question marks for PI candidates for those who failed SOC.
The question isn't why get frequent and sensitive viral load tests, but why not?
It appears early and frequent testing 4,8,12... is becoming the norm...here (again, I don't know about Ca.), for the most part the insurance co's will pay for the tests...falling under blood lab work, I've never really been able to find an exclusion clause in my policy preventing it with an r/x...and as you've said, the sqeeky wheel gets the grease...
I think trish was right on the mark with her questions and approach..but again we are limited by having to work within the system we're in , I'm afraid many don't realize what you have to go through to get extended treatment-if you can, it isn't anywhere near a given..In my experience and reading others we were all denied coverage as "experimental" and only under appeal got it to go through, if not and then only after being denied twice could one get aid from the drug companies...and all this is getting tougher everyday to get through the insurance co's....
soapboxing, sorry...pro
I guess I just hope for someone who is new here(I know you're not new Trish), they understand that much of what we discuss is not the norm..
I *will* be pursuing the option of getting in independent test done. Hopefully it's as easy as getting a script from my doctor, walking into the lab and forking over the cash to pay for it. Nothing is ever THAT easy but I fully plan to test it out this coming week. I'm going to make an appointment with my family doctor and explain to him what I want and why .. if he gives me the script, I'll walk the two blocks over to the lab and test the next phase.
If that won't work, I'll see if I can get the test done in the U.S., which is an hour and a half away from me and my family lives on the border. And I'll just keep trying through various means until I either get the test done or I have to finally accept that it ain't gonna happen and I'll suck it up. It does mean that much to ME.
I appreciate all the discussion and info here, I am finding it immensely valuable.
Trish
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I don't know what is the norm in Canada in general...there is SO much to learn about my own country and it potentially varies from province to province....but what is the norm at the clinic I go to is a 2, 4 and 8 week Quantitative PCR to a sensitivity of <50IU/ml and then a 12 week Qualitative PCR. Because of who they are - teaching hospital and all, I'm thinking that is not necessarily the norm persay. I don't know what they do beyond the 12 weeks...we haven't gotten that far yet.
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****....switch those two terms. 2, 4 and 8 week is QUALITATIVE. 12 week is QUANTITATIVE. Argh.
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That is precisely why I want Quantitative PCR's at 4 and 8 weeks. Not Qualitative. And that is precisely why I want an accurate PCR of my exact VL when I begin treatment. The Qualitative <50IU/ml will tell me if I'm below 50...then it's party time. If I'm above that, all I'll know is more than 50. I want to know exactly how much above 50...is it 55? 100? 1000? 10,000? I'll want to know. Then I can, as you say, gauge my response to the meds and respond appropriately..or simply know my reality.
Willing: If you don't have anything to compare against, the information from a vl test is of very limited value. For example, if you can find a study, any study, that found a significant effect in being UND<10 vs UND<50 at say week 4 or 8 then, and only then, would be reason to fret over missing that test. A key example is that there is now quite a bit of data showing that at w12, significantly different relapse rates were observed in 48week 1s that were UND<600, UND<50 and UND<10 so clearly that test has high predictive value.
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I'm reasonably satisfied with the sensitivity of the PCR at <50IU/ml at the 4 and 8 week mark and that is what I'll have. At the 12 week mark, if I've been <50 all along, I will want an even lower sensitivity and will likely ask for it.
Jim: Since I believe you are pre-treatment, do you mean "exact" or "sensitive"? Yes, it could be "thousands or millions higher" due to test variance, but within the context of logs it's important to have a pre-treatment viral load done to computer log drops during treatment as well as for predictive value where low viral loads have predictive values -- higher viral loads less predictive. The more sensitive tests become important once treatment has started to confirm UND.
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Hm. I mean, I want the exact number of how many of those critters are in my blood. How many of them per each ml. I didn't think about sensitivity but yes, I should also be paying attention to that and I don't know much about the sensitivity of assays at the upper limits. I just know mine is at the max of the one used for me, the 1.3mil. Surely there is one that goes higher than that? I keep seeing VL's higher than mine, so they must have a test for that...I think if I remember right, yours was 1.5mil when you started?
.........so my hat is off to you!!!
best of luck, pro
( I've done enough posting to last me a week!(g)
Harry
Well said and informative. It would stand to reason though that, with testing done to support this speculation, even in the absence of comparison data it would be reasonable to assume a 2 week RVR was better than a 4 week RVR, and a 5-week clearance was much better than a 12 week. These would have value to the patient who has to make a call on stopping early due to sx or other.
Bill, There are different schools of thought on this issue. I'm of the opinion that a low VL going in is indicative of a reasonably well functioning immune systsem and that's why these people have better odds. Artificially pushing VL down may have some effect, but it doesn't rewire your immune system, and thus is not as favorable as a naturally low VL. On the other hand, since the virus does muate against treatments, starting with a smaller pool from which it can throw it's mutations would seem to lessen the likelyhood of an environment that would support a viable mutantation fit for long term replication. I guess I've just said a mouththful of not much....
Sorry, when I posted to you it wasn't because we were in disagreement, it was just furthering a discussion.
Trish,
Not sure if we've been on the same page, but basically pre-treatment you want a QUANTITATIVE test that has a higher enough upper limit to give you a numerical read. The lower limit is less important in most cases so Bdna can be used as the lower limit is around 600 IU/ml and most of us start treatment above that. Once treatment starts, then you want again a QUANTITATIVE but ideally as sensitive as possible. I wouldn't worry about 50 IU/ml if that's the standard where you treat. Then once UND, you can switch to a more sensitive QUALITATIVE if you want. Here, some tests do all of the above. One example is Heptimax by Quest Diagnostics that can be used pre-,during and post tx. LabCorp also has one.
Bill,
We had a discusson recently about some sort of filtering device but not sure if it's available. I don't want to misquote HR, but he participated. As to Goofy's point, I'm not sure we really know if lowering pre-tx vl without boosting the immune system will equivicate to a low pre-tx viral load without intervention. My own theory is that our individual immune systems have their ups and downs and a low vl may coinicide with an up. I was over 30 million IU/ml one year and three years later 16,000. Same person, same immune system, just a different point in time.
-- Jim
Its the equivalent of walking up to the counter at Kroger's and asking the sales clerk for kleenex and having her say, "You cannot purchase kleenex anymore."
You might say something like, "But, why not? I have the money, and I need some kleenex!" Imagine if she looked back at you and said, "We have determined here at the Whitestone Rd. branch of Krogers that our customers don't really NEED kleenex so we will no longer allow them to buy it."
Shocked, you might say, "But many other stores carry kleenex for their customers. Why can't I buy it here, at my store? I'm the customer here! You're supposed to cater to me! I have the money to pay for it!"
You'd be REALLY stunned if the clerk said in response, "Regardless of whether or not other stores carry it and regardless of whether or not you have the funds to purchase kleenex, we won't provide that service for you."
We would NEVER tolerate such outlandish behavior. How long would people shop at that store? It would be out of business in a week.
Yet people let medical professionals treat them like this ALL THE TIME.
Doctor's sometimes get very discriminating about what they will and won't do when they ARE GETTING PAID by the very person to whom they are refusing reasonable care. And sadly, in some ways this happens because we keep allowing it to happen.
In Hepc treatment there are certain things that I personally would not ALLOW to be deleted from my care, and testing at particular stages, using tests with particular "sensitivities" or "ranges," falls into that category.
And I have to say, I have all the good people here on this board to thank for my rapid education on just which things ARE the absolutely "essential things in a treatment protocol for hepc - DO NOT GO TO A DOC WHO WON'T GIVE YOU THESE," and which things kind of fall into the range of "really great if you have a doc who will do these things also," and "wow, you're in a real swinging establishment if they're giving you all that sh*$!"
But truly, this board made sure that I knew what I needed to know about both testing and medical protocols before I went in to see my first doctor and I've been MOSTLY lucky with my doctors, although I'm going to tell you guys a story about one of my on call docs in a little while. And I always talk to my doctors about this forum. They've been pretty receptive to it in my case.
I am probably going to get rocks thrown at me for this, but THIS IS MY AND ONLY MY Feeling.
This is time 3 for me, I track my VL, I tract my levels. I understand the importance of being proactive with this disease and not just taking everyones opionions including the GIs as gospel.
I want to beat this thing, but quite honestly I am tired of obsessing over this, I want some quality of life, I want to be able walk away from it sometimes,
Getting a PCR every week does not really change so much for me, I feel I uses all my energy obseessing over it!
It is a virus that has its own way of attacking me, till they can totally corral it, I am at its mercy.
I am totally NOT saying DO NOT GET PCRS or VL.
Deb
Trish
Some people even get to carry on some exercising and things of that nature during treatment. I honestly think if I could get my blood count under control that I could do fairly well on treatment, because the day or two after transfusions I'm pretty ok.
The PCR:( polymers chain reaction test) used to determine if hepc is actively replicating and how high the viral load is; counts the actual number of viral particles in the blood. Being PCR negative does not necessarily mean that HCV has disappeared completely; it may still be in liver cells and in certain white blood cells. These can also be tested, although such extensive screening is rarely carried out. When it is, it seems that some patients judged to be clear of HCV by blood test alone actually still have traces of the virus in white blood cells, organs and liver. Although PCR has these limitations it is probably the most useful single test used to assess HCV.
The best indication is the 2 log or more drop at the beginning that determines if the strains and quasie species infecting you are being killed and kept from reproducing.
Canada has the best treatment success in the world. So follow the advice and proven proceedures of the Doctors that set the standards for the rest of the world. But get as educated as possible but not to knowledgable that you are overly concerned. I think you should relax and tell the Docs your concerns they will probably be able to put you a ease.
Here is the one of the best sites in Canada for everyrthing you need to know about hep.
http://www.hepcvsg.org/Chapter2.htm http://www.hepcvsg.org/Chapter3.htm#_Toc492622851
Hep c canada is also good, don't have the addy handy.
Harry
The myth that drs can somehow fine tune tx based on the results of vl tests bears no resemblance to reality - as I'm sure your Dr. will be happy to confirm. Personally I would be much more disturbed about an unwillingness to extend if your response is slow - the Canadian tx guidelines may be in the process of being adjusted in that regard.
Bill/Goof - I agree with Goof on this though I've never been able to find direct support for that theory. Overall, tx is sort of remedial training for an incompetent immune response. The lower your pre-tx steady state vl, the better the job it's doing of suppressing virus and the better the odds that, with a short stretch of summer school, it'll figure out how to do the rest of its job. If you could find some supplement/diet that systematically lowered your steady state VL you probably would improve your SVR odds, trouble is there doesn't seem to be any such supplement...
goof: speaking of supplements - what was the curcumin brand you finally sttled on? I didn't follow the end of your discussion with HR on that.
jim - the observation that "better clinicians are now ordering both frequent and sensitive viral load tests" may well be true but says nothing about whether those tests are of any use (unless you're suggesting that Drs A-Z have access to inside information they are withholding from lesser mortals). And I'm not sure I see any contradiction in your Drs changing his mind about w4 tests. A "few years ago" the w4 test was as uninterpretable as the week two is currently; by now we've accumulated enough w4 data to be able to assess its predictive value - but to say "it's fast becoming a standard part of treatment" for 1s seems quite a stretch - how many 1s have you seen here adjusting their tx based on their w4 results?
He wouldn't stop treatment at that time and wouldn't decide to extend at week 4. I was already on weight base dose, (really a little more riba) and by week 4 my hgb had dropped from 17 to a little under 14. I guess for me i was already under enough stress and just didn't need to add to it when it wouldn't have made a difference anyway.
Goof, while i understand your thoughts on stopping tx. early if sxs are to bad, does it really matter though? I mean if your not able to continue anyway you would have to stop no matter what. And sense this is a **** shoot anyway and the standard is 48 weeks unless i HAD to stop early RVR or not i wouldnt want to risk it.
But then again i relapsed so i dont know.
can do didn't
Loved the comment about lesser motals.
One of my concerns is that with extensive Vl's they follow protocal and do not continue to fight the virus. I have had friends who they have done that too, they then then stwitched Docs and ending up clearing. I do not always think there are hard and fast rules with this virus, it is insidious, Till they can clear it, antibodies and all, I will never feel confident about it.
A good friend of mine did not clear till after 7 times of treatment. She was aggressive and finally got there. So I am not a big fan of prrotocols that do not give me the right to be aggressive.
Ala~ You have had a tough road, I know..... I admire your courage. Are you on procrit? I have always thought transfusions were short term fixes? Are the because of your other anemia?
I think for me, that llife is sweet, my family, I so agree, that while I fight this we all have to give up some things. So the more normal I can make it the happier we all are.
It doesn't just affect me alone. maybe I just lived with it long enough to know it can be lived with,
deb
It's not necessarily ALWAYS the case though. When I started I remember a long time member explainning to me that she and several other low VL HCV txing folk had a helluva hard time reaching UND. Then came my turn, 568k starting VL and I did not clear until somewhere between 12 and 24. In fact, it's rather common for us to have a hard time even though this goes against what is logical or what we are told.
WE just notice this better because we have the low starting VL.
Low VLers often find trouble with a "plateau" - meaning a strong start almost to the point of EVR but then hit a plateau and cannot get rid of the remaining "few". As in my case. 568,000 baseline week 4 411 week 12 419. Had I not had the week 4 test I would have believed at week 12 that I had had a steady decline the entire time - but that was not the case. I hit the "plateau" and had to get off of it.
Is it sensible? no. But it's true.
ny: no arguing that that flattening is definite evidence of resistance, but in terms of tx planning did the week 4 test make any difference? The 419 at w12 is ample evidence of the need to extend.
I actually *do* believe there is much more predictive power in the vl decline curve than we currently make use of . If you collected weekly 1-12 vl stats for a large enough population, say 5000 patients or so, and gave the data to some electrical-engineeer/signal-processing types I bet they wcould come up with much stronger predictive algorithms than the simple-minded w4, w12 cutoff rules drs are slowly uncovering. There is information in the whole curve and any flattening in the slope, to the extent that it can be separated from noise, is indicative of resistance which likely bears on SVR odds. In fact roche/schering/vertex are collecting a lot of such data as part of the current drug trials - none of which they will release of course. Until this sort of analysis is available, and its predictive power assessed, getting more frequent tests is a bit like reading tea-leaves; yes, they're telling you something, but what?
So technically it did make a big effect on my course of treatment if for only at the time nobody said anything except 2 logs at 12 - UND by 24. Yes I got the two logs but easily enough even for someone like me saw that there was some major viral resistence going on in there for some reason and that is what I wanted to extend for - that plateau.
Had I been UND at 12 in addition to the 2log (of course doy!) I would have been very content with doing the 48. But see - I had already just started reading both of the studies (and even at that time HALT was out) and started my brain on the "should I or shouldn't I" thought process. With me once the light goes on.............it's hard to turn it back off.
It turned out it was the right thing to do regardless but going by the "old school" way doctors decided these things.........we never would have known.
Literally I feel that the studies popped onto our radar in the nick of time for me.
My viral load came down over 4 logs after 4 weeks, and my doctor thinks this is incredible and thinks I should just do 24. I am disappointed they gave me such a poor test after 4 weeks, if I were under 50 by PCR my decision would be clearer.
I did read that the degree and speed of the decline was important to consider (I will look at the article). I do think that cut off at 4 and 12 for these important decisions is limiting.
I learned from her to never give in and never ever give up!
My worry with all this is that they only follow protocol, I can see the reason for Vl, the use of it to be more aggressive. But see the immune system playing a huge part in this also.
Viral infections do not always follow the same rules as other illnesses.
NY Sis, where are you?
I learned from her to never give in and never ever give up!
My worry with all this is that they only follow protocol, I can see the reason for Vl, the use of it to be more aggressive. But see the immune system playing a huge part in this also.
Viral infections do not always follow the same rules as other illnesses.
NY Sis, where are you?
Willing ... I am one Geno 1 that WOULD advocate for a tweak my treatment based on a quant 4 week VL if the results warranted it. (Not in a drug trial of course, regular SOC). And I'm sure there are more who would as the signficance of this becomes more widely known.
As for tweaking ifn/rbv dosage based w4 decline, there's no reason not to try, but, to the best of my knowledge, there's zero evidence indicating it'll do any good. Unlike the newer drugs, IFN doesn't do anything that directly interferes with the virus; it merely activates various pathways, like PKR, that interefere with viral replication. In that respect it's a bit like a car-alarm. Whereas the success of daily infergen and pegylated vs thrice/week ifn indicate it's important to keep the alarm ringing 24/7, there does not seem to be any advantage to just ringing the alarm louder. The actual job of shutting down viral replication and killing off infected cells falls to one's own B&T cells - which may or may not be able to pull off the job. You can find quite a bit of data on pubmed on recent induction (high starting dosage) studies, without any clear cut benefit. If you find anything supporting on-tx dosage adjustment based on vl results please post it...
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Feeling comfortable cutting my tx short because of a quant 4 week RVR doesn't negate the benefit of having one. It's a benefit *period* simply for the information it presents throughout the duration of treatment for how one is responding ongoing. Some of the people posting in this thread have mentioned where a quant 4 week PCR has been, or would have been, of benefit to their big picture. As for my own comfort level, at the current moment, no...I wouldn't cut it short. However, I would like to see it become standard.
If I had terrible side effects ....an RVR at 4 weeks would be a deciding factor on whether I stick it out to 26 weeks and then stop treatment rather than dropping out earlier. I see a number of positives for quant 4 week PCR's .. and virtually no negatives.
Incidentally, I'm being screened for a drug trial currently where this is at least one of the arms.. if you RVR at 4 weeks, you'll stop treatment at 26 weeks and yes, I'll agree to that. I think this study is significant and I'll take the chance of being in those arms. I'm Grade 1 Stage 1 and I have some time.
As for your remaining comment in response to me saying I'd be asking to have my treatment tweaked if a 4 week quant VL test suggested I wasn't responding as well as I'd like......plenty of studies suggest that the level of ribavirin prescribed has an impact such that it's become pretty much the de facto standard to use weight-based ribavirin rather than a standard dosage. I've read various studies where the difference between a standard dosage of ribavirin and weight-based ribavirin has been obvious. If I need to post these studies, I will...however, I think that's generally accepted by now, is it not? I don't think I've seen any studies that measure *specifically* where an increase in dosage during tx results in better SVR...moreso the impact of higher dosages of ribavirin as opposed to lower dosages. That is sufficient for me to ask for an increase.
I don't know enough about the impact of higher or lower doses of Interferon so I won't speak to that, something I need to look into in more detail, particularly since the trial I'm hoping to get into doesn't mess with ribavirin levels but does have different dosages of INF in various arms. So...as for tweaking...I'd be looking to up my dosage of ribavirin as long as my body can take it and if I don't have Alinia in the mix as yet, I'd make an extra effort to add it. Beyond that...not sure how much tweaking can be done, but yes......I would at least do that much.
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The literature seems mixed on induction dosing. The "Repeat" study shows more EVRs but similar SVR stats. The following study, however, shows benefit in fixed-dose induction for treatment experienced true non-responders, and anecdotally a number of doctors have used double-dosing with success as part of individualized treatment which is difficult to trial because it is individualized.
"Conclusion: Fixed-dose induction of peginterferon α-2a resulted in increased drug exposure and improved the likelihood of achieving a cure, without compromising safety in hepatitis C virus genotype 1 true non-responder patients."
http://www.medscape.com/viewarticle/563952
Somewhat related, there is an hypothesis that induction dosing, even if ends up not correlating with SVR (a tx naive study is still pending where again there is a more vigorous viral response) may show benefit when in combination with a PI in triple therapy -- reason being the importance of an RVR in those studies. This may also turn out to be an avenue to explore in the case of prior SOC non-responders who enter triple therapy, as per previous discusions with "Susie2007" relating Dr. Sh's concerns for these patients on triple.
As to "tweaking", "Trish" speaks well to this, indeed well on the entire issue. We have many studies that suggest RVR correlates positively with SVR. Also studies that show SVR elusive without at least EVR. We also have studies that show that riba-dosing can affect both RVR and SVR.
Putting it together, it then seems reasonable that early VL testing can pick up slower responders and one option might be to increase the dosage of the tx drugs -- riba in this example -- if certain criteria are in place such as slow hgb response in lieu of lack of HPLC serum riba testing.
If the xtra riba can then help achieve either RVR (or EVR) in patients who might not normally do so -- then in effect it might help with SVR. Similar strategies might work with increased and/or changing interferons in slow responder scenarios although this seems a less common approach in-treatment. One of our members, "Fishdoc" is just one example of someone who had both a slow viral and slow hgb response who then responded after her doctor increased the ribavirin based on equating her slow viral response with a flat hgb curve.
Not surprisingly, study data is sparse or nil on "tweaking" because this is all part of individualized treatment which by its very nature is difficult to trial. Another reason is that study data re customized riba dosing is sparse as well in this country and no doubt the lack of HPLC serum riba testing is one reason.
That certainly doesn't mean i"tweaking" t's not a viable option in the hands of a good clinician who is trying to cook the very best treatment soup for a particular patient in a complex and fast moving field where study data can only be a guide but not a road map. Someone posted that someone said HCV treatment is as much art as science -- and these days, and so it appears to be for now.
As to prior discussion about real-world patients changing tx decisions based on a week 4 vl test -- I think we have many including those geno 2's and 3's (and I believe at least one geno 1) who decided on a shorter course based on RVR, as well as those like "NYGirl" who posted how her week 4 test factored into treatment. And then again, the ability to "tweak" oneself into a faster viral response. There are also studies suggesting that 72 weeks may be a viable option, not just in the case of EVRs but also those without RVR. And, as previously discussed, early vl data also can help in future re-treatment scenarios as newer information comes on board. Dr. Sh's take on PI's with tx experienced prior SOC non responders is one example where he contends that one could be EVR (a responder) even if a two-log drop does not occur by
week 12 (standard definition of EVR) if a two-log drop occured sometime prior to week 12. But if one only tests at week 12, a certain number of these "EVRs" would be missed, so Dr. Sh contends.
-- Jim
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transfusions are most definitely short term fixes, and the cumulative damage from them isn't good due to the residual iron. I'll have to work that part out after treatment. However, on my dose of tx meds (the riba in particular), I have not been able to raise my red blood cell count at all, even on 80,000 units per week of epogen. So I've had to rely on transfusions every 10 - 14 days everytime it looked like my hemaglobin was headed south of 7hgb. And my regular anemia is easily maintained on small amounts (8k - 12k epogen every 2 or 3 weeks) of epogen. The transfusions have been necessitated by ribavirin induced hemolytic anemia. There is the question of why that hit me worse than other people since its not the same as my other anemia, and the answer to that is unknown. Somehow, that first type of anemia made me more susceptible to the tx induced issues. I don't have a good answer for it.
willing - there's no arguing with the fact that the predictive value of the w4 test fors 1s is currently an active area of research - and abbreviating tx for 1s who rvr is one of the questions being investigated. But would you feel comfortable cutting your tx short until those results are in and confirmed?
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I thought that under some circumstances, there is some confirmation of this for 1's
Thanks
Deb
jim: "treatment which is difficult to trial because it is individualized. " that seems to be the crux of the issue. There's no shortage of alternatative strategies and adjustments/tweaks out there but do they actualy do any good?
Against the very high level of background random variation inherent in tx, I think one should be skeptical about assuming an alternative approach increases one's svr odds. That is, evidence should be more compelling than faith in a good physician or anectodal results. Of course, in the face of how little we know, there's plenty of reason to experiment with one's own tx... but in an experiment you know that you don't know the answer.
Do you recall whether fishdoc was on wbd before the increase? I agree that adjusting rbv dosing if there's evidence of inadequate dosage seems the right way to go. However vl seems a very poor indicator in that regard (hgb drop not much better but probably a bit more reliable). Apart from all the noise inherent in a vl reading the prevailing view of rbv's contribution is that it kicks in late in tx as ifn efficacy tapers off eg
http://www.ncbi.nlm.nih.gov/pubmed/17484896
So rbv's main impact happens long after vl is und..
Overall, I think we both agree that exact match study data is difficult -- not just here but with so many tx scenarios -- but I really believe that we can extrapolate enough from the existing studies to come up with reasonable treatment strategies, and the best clinicians are the ones that seem to be doing it, and that's where I would want to be -- and where I was -- when treating. Of course, if one has the luxury of waiting to treat, the data base will only become more complete.
So when you say "one should be skeptical about assuming an alternative approach increases one's svr odds" , I would substitute the word "hopeful" for "skeptical" at least with certain tx approaches that have study data if not directly behind them but at least just off to the side. Individualized tx in this respect does not offer guarantees, but it does seem to be the best approach and frequent and sensitive vl testing seems to be part of that.
Anyway, the question remains, is there a single g1 on this board for whom the results of w4 or w8 tests (or of any tests between 1 and 12) resulted in a meaningful change in tx direction?
I appreciate nygirl's comment that for her the berg/sanchez-tapia data came in the nick of time, but the point remains with the data available now a vl of 419 at 12, in fact any vl at 12, is grounds for extending, regardless of w4 results.
jim: my point was that though neither vl nor hgb levels are good proxies for rbv serum concentration, vl seems, by far, the more unreliable of the two. If you find any data showing a reliable correlation between rbv concentration and vl please post ...
The only thing that week 4 vl changed was the ability to become more aggressive with it.
I am doing pcr today, so will let you know.
My Nurse from drug Company was advised by Drug company that at Week 4 Vl, is very often not accurate, the meds have had not time work. Of course it is the drug company who wants me to buy drugs.
Deb
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You may not get a yes answer to that now although you could. Ask again in a year. I do believe the significance of RVR at 4 weeks is just starting to become apparent and therefore so is a quant PCR at 4 weeks as a result. I think we'll see treatment evolve by the same token as this sort of information becomes more well-known.
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I guess it depends where you're coming from and who is the source of those "urban myths". For example, "Fishdoc's" author was a well-respected hepatologist. And in the case of another unsupported tx approach -- tapering off interferon -- the author is "HR". Go to Clinical Options site and you will see many urban myths if your defintion is non-conclusive study data.
Willing: Anyway, the question remains, is there a single g1 on this board for whom the results of w4 or w8 tests (or of any tests between 1 and 12) resulted in a meaningful change in tx direction?
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You've now narrowed the field now down to "geno 1's" as I pointed out that a number of geno 2's have altered treatment -- shorter course for example -- based on the week 4 test.
But yes, NYGirl is one case, and not sure if the data you are talking about was available to her then. But another case is myself. Being UND at week 6 was the key point that two well-known doctors (and my NP) pointed to as the basis for not extending tx to 72 weeks. I also remember others pointing to RVR as a similar basis for stopping at 48.
"Fishdoc", assuming she is geno 1, is one more example. Then there are the one or two geno 1's who did short course based on RVR and some others -- results pending -- who mentioned increasing riba doses based on flat hgb reponses. And I'm sure I'm missing at least a dozen or more other cases. But regardless, the fact that the majority here who have completed tx weren't tested before week 12 doesn't mean it isn't the right thing to do. In fact, I'd guess that when I came here over 2 years ago, maybe less than 10% had a week 4 test, now I'd say it's closer to 50%. Have about run out of points on this matter and frankly I don't think either of us have added anything new that we haven't discussed before, not that I mind chatting with you every once in awhile :)
Willing: my point was that though neither vl nor hgb levels are good proxies for rbv serum concentration, vl seems, by far, the more unreliable of the two. If you find any data showing a reliable correlation between rbv concentration and vl please post ..
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I just mentioned that studies have been posted showing that riba concentrations are associated with RVR and SVR. In my mind that's a correlation between rbv concentration and VL, i.e RVR. If this is what we're talking about, I'd be glad to look for the studies again. .
My week 4 test was 2900 IU/ml - a log drop of 1.62, which indicated I might become a slow responder.
I would gladly have taken an extra ribavirin pill each day after receiving my week 4 test for the hope of becoming UND by week 12 and thus saving me from extending tx to 72 weeks. Since I was so close to UND, isn't there a realistic possibility that the extra ribavirin pill might have done it?
http://www.hivandhepatitis.com/hep_c.html
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From Clinical Care Options (free reg required)
http://tinyurl.com/create.php
Program and abstracts of the 42nd Annual Meeting of the European Association for the Study of the Liver; April 11-15, 2007; Barcelona, Spain. Abstract 619.
Week 4 Plasma Ribavirin Concentration Independent Predictor of SVR in HCV-Infected Patients—Optimal Cutoff Suggested
Posting Date: April 14, 2007
Sustained virologic response (SVR) in patients receiving peginterferon plus weight-based ribavirin for HCV infection
o SVR rate: 86%
* Achieving SVR at ribavirin plasma concentration > 2 mg/L likely due to early HCV clearance in these patients
o Early virologic response (EVR) in this group: 100%
* For patients with Week 4 plasma ribavirin < 2 mg/L, ribavirin dose increase possibly warranted to increase likelihood of SVR
____________________________________
In summary, RBV plasma levels correlate with the development of anemia and with the achievement of an early virologic response. Therefore, early therapeutic drug monitoring might help to tailor RBV dosages, improving the efficacy and safety of anti-HCV treatment.
http://www.cababstractsplus.org/google/abstract.asp?AcNo=20053157702
Monitoring ribavirin concentration predicts early response, anaemia.
(Paid access only)
http://tinyurl.com/2449ae
jim : I restated the question asked in a post above "how many 1s have you seen here adjusting their tx based on their w4 results?"
perhaps some of those who actually changed tx direction based on 1-12 tests will post.
Tapering-ifn easily belongs among the "hopeful experiments" category: there's a rational argument in its support and no data. The important difference between an experiment and a supersition/urban-myth is the assumption that a particular approach has been demonstrated to help versus the simple hope that it might help.
I have no idea what fishdoc's testing schedule was, but your week 6 decision seems quite unusual - maybe that's why you are so in favor of weekly tests. The implication seems to be that your drs/np were able to estimate svr odds based on week 6 results (on the basis of what?) and infer that extension to 72 would not have changed those odds (on the basis of?) .
Anyway, if you come across data correlating rbv dosage with rvr please post - it would seem to contradict Perelson's point about rbv effectiveness in relapse prevention at eot.
"Induction did not increase SVR compared with non-induction, but did increase the on-treatment response among genotype non-1 patients in Study 2"
from
http://www.ncbi.nlm.nih.gov/pubmed/17845540
On the other hand for the new, hcv-specific, meds, rvr seems to have as much predictive value as garden-variety soc rvr. Whether upping your rbv dosage would have helped you get to und/12 and done so without affecting the predictive power of und/12 is a good question... and probably will stay that way... but I hope your countdown's going well (and thanks for the note about g1 specificity of 950 - still want to check that out)
jim: thanks for the two studies. The hiv/hcv one may or may not apply generally, as hiv coinfection is particularly difficult ( I have no idea what effect rbv has on hiv itself). However the Maynard EASLD'07 study, though it only included 22 patients, seems to show a definite effect of rbv on early tx/rvr outcome.
The accepted view is that rbv play its major role towards th end of tx :
"Ribavirin appears to enhance SVR by both enhancing virologic response and
reducing relapse. In those studies where standard interferon or peginterferon
monotherapy have been compared with combination therapy with ribavirin,
virologic response increased from 24% to 50% and 59% to 69% respectively.1
and 10 However, the major impact of ribavirin is to reduce relapse, which
declined from about 45% to 51% in patients treated with only interferon or
peginterferon to 18%–24% in patients who received combination therapy.1
and 10 As a result, the addition of ribavirin has led to a marked increase in
SVR from 13% to 38% in patients treated with standard interferon10 and
from 29% to 56% in patients treated with peginterferon.1 The mechanisms by
which ribavirin acts to enhance response and reduce relapse remain
obscure. "
from
http://www.ncbi.nlm.nih.gov/pubmed/17030201
so this is interesting counterpoint to the conventional wisdom. However if you believe drs can meaningfully adjust rbv/ifn dosage on tx based on vl results it would be good to see some data that supported that.
To answer your question, if I were starting soc tomorrow I would certainly test at 4 and for the reason Trish suggested: quitting if I wasn't rvr. If quitting were not an option, eg because I found I was now at stage 3 and could delay no longer, I would only test when the outcome might yield a decision, and, as best as I can tell putting all forward-looking statements aside, today that still means w12.
BTW - not sure I understood your last comment. The definition of rvr is und/4 how is und/6 interpretable as rvr?
As to my week 6 "RVR", because my VL was tested weekly, my docs had more data than with study patients, who for example tested only at week 4.
My week 1 viral load drop was a tad short of 2 logs. Week two I was <600 via Bdna because at that time I didn't know enough to ask for a more sensitive test which I did at week 3.
Week 3 I think I was around 53 IU/ml more or less from memory. Weeks 4 and 5 my VL acutually went up incrementally to around 150 IU/ml.
I was hoping that the upswing was because I had to go off riba for a week (ended up in ER) but worried of a viral breakthough which can happen even very early un. Then UND at week 6 and a very big sigh.
The reason my doc's called it RVR at the plate was no doubt because I was so close and also heading toward UND and might have made it if not for the riba break. While you never know, I doubt my numbers were typical of an EVR. Anyway, as you know I did end up tx another six weeks (to 54 weeks) and no doubt I factored in the xtra two weeks it took me to get there. If it turned out I was only EVR, I'm sure 72 weeks would have been the plan. Probably not as neat a construct as you would like, but that's where my med team and myself came out.
-- Jim
who knows if it ultimately will or did make any difference, but my riba dosage was adjusted higher (twice) as a direct response to pcr results and hgb.
Details in my profile...I agree that any data is sparse in this regard. As a side note, my doc does routinely adjust dosages, but he is pretty agressive...he is also involved in the Roche induction study, whether or not prelim. results from this study have played a part in his tx approach,I don't know..
Pro
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JMO of the basic question, most people know nothing when first starting treatment and rely on the doctors experience in the treatment. Patients only become Monday morning quarter back after the fact that the time has passed to correct anything from the beginning.
It would seem to me that if you had a PCR just prior to the start of treatment to get your baseline viral load and other CBC counts you would have your base line numbers. A lv count at 4 weeks would be useless either way, why? because (most competent doctors) would use a standard pcr test even if it’s down to <50 at this point. A 4 weeks vl may or may not show true vl decline again because the meds have not fully loaded into your system IMO it takes at least 6 to 8 weeks for the meds to reach an optimal concentration point and in that time the vl could be all over the scale. I would think that the 8 week pcr test would tell a more clearer picture of what is and is not working and this is if you had started at the top of the standard SOC treatment, 180/1200. Of course there are a lot of variables but this is what most (main line) people start out with.
Bottom line is that the 4 week PCR will give you nothing except peace of mind. The 8 week PCR on the other hand will tell the greatest progress to that point and if you’re above your bottom PCR marker then this is where adjustments can be made. What else can you do if you are at max meds at week 4?
jasper
pro: I used excel to keep track of my test results for discussion with drs. It can do arithmetic on dates and easily output a data plot in html format suitable for web viewing. It seems much easier to communicate trends you want to discuss with your dr when you're both looking at the same graph..
Your comments about yor dr's adjustments are interesting. As Jim pointed out, that's possibly a separate topic from the original VL question, but the two seem related. What seems remarkable to me about your dr's changes is that as best I can tell this is very much an active area of research and that even in studies using HPLC-based measurements of rbv concentration the predictive value and optimal level are still controversial.
For example, in the discussion article accompanying
http://www.ncbi.nlm.nih.gov/pubmed/17412448
the authors point out that
"The authors show that plasma ribavirin levels were significantly lower in sustained virologic responders (SVRs) compared with non responders during the first week of treatment. During the same period, hemoglobin decline was significantly deeper in those with lower plasma ribavirin levels, the same as those who were more likely to achieve an SVR."
The underlying (unproven) assumption is that plasma levels are lower because rbv, in its active triphosphate form , is captured in cells rather than floating around in plasma. Thus the hgb drop associated with rbv wreaking havoc in erythrocites (rbcs) is the more telling indicator.
On the other hand, in another study:
http://www.ncbi.nlm.nih.gov/pubmed/18238889
a correlation of trough plasma rbv concentration with evr and svr *was* found for 1s:
"However, in patients with genotype 1 or 4, ribavirin C(trough) was independently associated with EVR (P = 0.036) and SVR (P = 0.046)"
this is all research published in the past few months - and does not seem to give any clear guidelines for dose adjustment - though it does underscore that a flat HgB curve after starting rbv is probably not a good sign.
Also, with respect to alternate predictor formulas : the results in Dahari'07 are pretty impressive. For those sitting on the fence their formula
(ALTd7/ALTd0 + 0.7 log10HCV RNA)
seems to give 100% negative predictive value for the cost of 1 week of tx!!
graph and data (missing 2 CBC/LFT reports)
http://www.nces.ed.gov/nceskids/createagraph/graphwrite.aspx?ID=f5f2855ad73b46459cc5474c119c7e81&download=false&file=table
The other day I told the Docs treating me for 1a of a new drug that's in trial that cleared the virus in two weeks in 85% of the people. They responded by saying that conventional treatment does that or better and spouted off tons of stats on weeks one thru 48, so they know this all ready and have simplified things to were they are today, prior to,12,24,48 and post 6 months this is for early stage treatment of course and later stages or people with complications require addition monitoring but treatment should still not be adjusted untill week 24 unless you can't handle the side effects.
Harry
http://www.ncbi.nlm.nih.gov/pubmed/10733558
(basically hogs all the atp ) so the fact that your hgb responded quickly to the 1st and 2nd rbv assaults but slowly to the 3rd is a bit strange. At 170lb/77 kg weight-based dosing would have you at 1000. I suspect your dr looking the december'06 hgb of 16 thought it looked a bit too healthy and upped the dose.
It's unfortunate that though the plasma rbv studies clearly show the correlation with hgb drop there don't seem to be guidelines for how much of a drop indicates you're at the "right" rbv dosage. Anyway, looks like you are on the right track , both with respect to the extension and the rbv increase. Regardless of whether the w4/w8 VL tests contributed useful information (the w12 alone would have been reason to extend) your data underscores the importance of monitoring hgb levels - particularly until a more reliable indicator of rbv concentration comes along.
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Or for a a 1 who has significant liver damage and might want to extend, or for a 1 who has little liver damage and might want a shorter course, or as a reality check/incentive, etc. for either genotype if they have to make a difficult decision down the road because of sfx. Or.for those who think the info might be valuable down in a possible re-treatment scenario, either based on current understandings or data from future trials. And I'm sure I've missed some other reasons.
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Willing: However, the faith you place in your drs to correctly interpret data is impressive - to me a vl of 150 at w4 and 5 wouldn't qualify as an rvr regardless of what any dr said...
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By now you should know that I'm the last person that puts "faith" in any one source or opinion because the buck stops with my liver and therefore my decision. I looked at study data, my doctors offered their opinions, and I made a decision what to do. As stated, my VL was tracked weekly and the pattern, given the temporary riba discontinance, appeared to be RVR, plus apparently my virus did not read the studies and penalize me. Again, tx today is part art and part science, but if you want to call that reading "tea leaves', go right ahead. I'd still want my tea leaves read by those with the most knowledge and experience and frankly if you think the whole tx process -- even with "by the book" protocols, isn't part "tea leaves" , then I don't know what to say, except again, it's been nice discussing things with you and have a good weekend.
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I need to correct your interpretation of my comments and how you got this, I have no idea. I not once, not ever and don't...suggest that people should determine stopping treatment based on an RVR at 4 weeks. I said quite a few things about how a quant PCR at 4 weeks could be applied but this was never one of them. The closest thing I said to this was that ONE of the ways a quant 4 week PCR could be helpful was for those persons experiencing great difficulty with the side effects and who are facing 48 weeks of treatment. For those people, currently...SOC is 48 weeks even with RVR. And if the side effects are brutal for them, 48 weeks may be unbearable. So perhaps rather than dropping out at 13 weeks or 19 weeks, an RVR may encourage them to go on to at least 26 weeks and thereby giving them a greater chance at SVR without doing the duration. 26 weeks may be bearable to them. 48 weeks, not. And if successful, they may not have to come back again for another round. THAT is the closest I said to your interpretation of my comments. Whew.
As for the rest of it......the posts continue to come in from persons who would have benefitted from early quant PCR's in various ways. They also are coming in from persons who would have tweaked their treatment in whatever small ways ARE possible to us. You are entitled to your opinion. However, the body of evidence continues to grow on the benefits of early quant PCR testing.
Geterdone.....interesting comment on the 4 weeks vs 8 weeks and potentially too much to quote here for response, but I'll see....
For me personally, I don't consider myself to HAVE a baseline as yet. They've given me my VL which happens to be at the upper limit of the assay they used. To me, that is NOT a baseline. A completely accurate VL would be a baseline, not just "somewhere above 1.3mil". I'm personally not happy with THAT.
I'm not sure I agree with you that a 4 week PCR doesn't give you any accurate information. The studies that are out there at the moment are taking into account 4 week results and RVR at 4 weeks has been seen to be a predictive factor in SVR and whether one treats to 26 weeks or 48. (Before anyone jumps on me, NO...I'm not advocating stopping treatment at 26 weeks across the board with an RVR. Just repeating SOME study results. )
And if you are NOT at the max of your dosages...and I don't think many start out that way, at max....then a 4 week quant PCR is quite useful considering that you only have 8 weeks more to go to get to that magic 12 week mark where they determine whether they want to discontinue or proceed.
Your comment though...re the accuracy of 4 weeks vs 8 weeks is an interesting one. Gives me something more to chew on for awhile. :)
- 1s start with about a 50-60% odds of svr (averaged over factors that push those odds up or down)
- if und by week 4 (on soc) those odds go up to 85% or so
- if no 2-log by w12 they drop to under 5%
- if 2-log by w12 but detectable, the ordinary relapse odds of 25% are about double and may be restored to the "mainstream" odds by 72w extension
-if still detectable at 24, regardless of previous drop, the odds are under 5%
As Jim points out , this all whole business is painted in shades of gray. However there is a difference between calibrated and uncalibrated indicators. The predictive value and statistical signiicance of the above indicators has been analyzed and confirmed ad-nauseam. On the other hand the predictive value of, say, a 6 week test, is in the eye of the beholder.
This forum often includes posts from people wondering whether to jump into the pool given those chilly 60% odds. It occurred to me that failure to rvr is another reliable use of the 4 week test - which apparently is not at all what you meant. Sorry about that. My intial point was simply that I believe there is good reason for drs/ins. cos/med services' reluctance to order tests not sufficiently calibrated to affect tx outcome - it's not a question of being ill-informed, which often seems to be the assumption around here.
As for the previous posts, please correct me if I'm wrong, but I see none that indicate a change in tx different from what would have resulted based on w12 testing alone (for nygirl and proactive w12 were grounds for extending and I'm assuming, perhaps incorrectly, that Proactive's rbv adjustment was due to her small hgb drop).
jim: well as usually happens around here, there's not much resolution, but thanks again for those rbv link. There does seem to be a new interest in determining proper rbv concentration. I don't know if you noticed this, but one of the implications from Dahari'07 is that hplc-based testing would not necessarily help - perhaps better calibration of the hgb drop is the more reliable indicator.
-- Jim
There is a new study on high riba dosing in hepatitis C treatment being done at Karolinska University Hospital in Sweden. Docent Robert Schvarcz seems to be a name to keep an eye on in this context.
"Dr. Karin Lindahl, who recently defended her thesis, has continued to study ribavirin from a clinical perspective with focus on patients with healthy kidneys. In a recently published piece of work she has pointed out a connection between the concentration of ribavirin and the degree of anemia, the most prominent side effect of this drug. This is a clinically valuable observation of importance for dosing this medication. We also have an ongoing pilot study of patients with chronic hepatitis C of a more difficult-to-treat patient group, i e genotype 1. In this study patients receive high doses of ribavirin and the question at issue is how the drug will be tolerated and how to handle side effects. The hypothesis put forward is that high doses of ribavirin increase the efficacy of the treatment."
From
http://ki.se/ki/jsp/polopoly.jsp?d=16180&a=36564&l=sv
(Updated 2007-07-25)
My ex talked to his doctor in the study he is in, RelapC, in which HPLC-based testing of the plasma ribavirin concentration is being done regularly. Unfortunately these results will be blinded to the patients until RelapC is completed. HPLC-tests of plasma riba concentration are analyzed at the laboratories of Karolinska University Hospital in Huddinge, Sweden and Odense University Hospital in Odense, Denmark.
Dointime, I know you wanted contact information. Here is information on how to contact these two university hospitals:
http://www.karolinska.se/templates/DivisionStart____53585.aspx?epslanguage=EN
http://www.ouh.dk/wm219813
http://www.ouh.dk/wm122110
Interesting, because Lindahl published same thesis a number of years ago in what I remember to be Le Drug Monit (or something similar). I pulled it from a medical library and have not been been able to since find it on the internet. Not surprising that anemia and serum riba concentrations are related, although a much cruder barometer than actually measuring serum riba levels with HPLC. As to the toxicity issue of high dose riba, that's always been the big problem and with the progression of the PI's hopefully it will soon be a moot issue. But meanwhile, while SOC still rules to a large degree, riba and its dosing seem an important component of SVR.
-- Jim
"During the first 4 weeks of treatment, median plasma ribavirin levels ... were significantly lower ... in sustained responders compared with nonresponders."
(presumably because svrs somehow managed to increase the amount that makes into cells..). So hplc-based measurements of plasma concentration may not be that much of a help after all..
jim : is this ( the original Lindahl paper) what you are referring to ?
http://www.ncbi.nlm.nih.gov/pubmed/15660393
Harry trying to understand.
No, that was their 2005 Piilot Study that got all the attention. Lindahl and her group have been studying/publishing on riba long before that. Here's an 2002 paper, for example, on riba dosing based on renal function, as opposed to wait.
http://www.ncbi.nlm.nih.gov/pubmed/12451285
There, Lindahl discusses a pharmacokinetic formula that pre-dates the one used to set initial riba dose in the study you reference above. The study I was referring to I believe pre-dates even this one and discusses using anemia as barometer of serum riba levels as best I can remember. The publication again was "Ther Drug Monit." and at the time I got the article from a medical library and since unable to find on the net. They have been at the riba thing for a long time. I do remember even paying for the article at the Library for some reason so it might not even have been on their main computer but can't remember exactly as I had just started riba myself :)
Harry, Yes, there is a inherent variable in HCv RNA assays, even higher than that I believe per Dr. Mitchell Shiffman's slide presentation over at the Clinical Options Web site. No reference to qant vers qual so I don't think an UND qual with a sensitiivty of 5 IU/ml is any more accurate than a quant UND of <5. both would be UND to the limit of the test.
-- Jim
Looking back should I of asked for an increase of Riba from 1000 to 1200. My DR asked my weight at the beginning of tx which is 190 and then wrote a script for 1000 ml of riba.
Bobby
At 190 lbs, you just entered the 1200 mg./day dosing range but maybe your doc played it conservative since you weren't a geno 1 -- as he just as easily could have given you 1200 mg. (I started at 1200 mg/day and weighed 176 but was a geno 1).
In any event, you had a significant drop in hgb so one might assume that the current dose is getting into your system efficiently and frankly I'm surprised such a drop didn't land you flat on your back. BTW there's a "helper drug" called Procrit (epo) that helps many of us function better with low hemoglobin. If your symptons are persisting something to talk to your doctor about.
The low range for hgb on my lab report is 13.2, but keep in mind that most of us are anemic to one degree or another on tx.
-- Jim
(http://www.ncbi.nlm.nih.gov/pubmed/17412448)
"We also evaluated hemoglobin declines stratified by treatment outcome. Although median baseline hemoglobin levels were roughly equivalent in SVRs and NRs (p = 0.20), hemoglobin decline during the first month of therapy was significantly greater in SVRs than NRs (3.9 vs. 1.4 gm/dl, p = 0.002) "
all: the rbv mystery deepens...writing last July in a review comparing two recent assessments of rbv's effect as an hcv mutagen, Perelson, maybe the world's leading hcv kinetics expert, closed with:
"In summary, both papers[1] and [2] demonstrated that RBV has an early effect in elevating mutation rates, consistent with the mutagenesis hypothesis. Although further tests, using infectious HCV clones or additional sequencing may be performed, the proof may be in the pudding. If RBV is acting mainly as a mutagen, then according to the Dixit et al14 model, it should have little effect in combination with therapies that efficiently block viral production. If a lack of effect of RBV could be shown for combinations of IFN with effective small molecule HCV inhibitors, we can stop arguing about RBV’s mode of action and simply remove it from future therapies."
(from http://www.ncbi.nlm.nih.gov/pubmed/17484896)
however... it looks like the arguing will go on for quite awhile to come since, as summarized in that quote by Jacobson that mike posted in the r-1626 thread above:
"this study also showed that ribavirin contributes significantly, just as it did with telaprevir, to the antiviral activity seen with combination therapy containing R1626."
not only is rbv not going away, neither the mechanism of its effect nor the proper way to gauge "optimal" dosage seems to be coming into view.
One interesting point, and perhaps others can tell me if I'm hallucinating or not,
but from both Fig. 10 of Lindahl's dissertation (thanks zazza) and Fig 1a of Dahari'07 (free access) it seems that the striking difference in rbv plasma levels between svrs and nrs is not so much the mean as the variance. The svrs all cluster around one level whereas the nr values are all over the map...
http://www.ncbi.nlm.nih.gov/pubmed/10508023
(free-access) with respect to rbv kinetics, and they largely agree with your pharmacist. The effect of taking a new dose seems to peak in about 90 minutes "a time to Cmax of 1.33 ± 0.034 h after oral dose administration". Decrease of plasma concentration varies across individuals, but as shown in Figure 2 of that paper is 0 or near 0 for most after 75 hours.
An important detail however, is that plasma levels don't tell the whole story. The rbv in red blood cells is *not* cleared and the rbv molecules stored there will go back into circulation when the rbc dies off. The wikipedia rbv article
http://en.wikipedia.org/wiki/Ribavirin
puts total turnover of one's rbcs at 6-months. I didn't follow this up, but this detail seems to account for the 3 day vs. several month discrepancy.
Interestingly, Lindahl also casts doubt on the "take it with fat" recommendation:
"The extent to which food affect ribavirin bioavailability differs between studies. It is also unknown whether any food effect might be altered by the type of meal consumed (e.g. high versus low fat content), if a food effect still would be evident upon multiple dosing and what clinical implications this might have (79)."
though more recent data supports the peanut-butter chaser:
http://www.ncbi.nlm.nih.gov/pubmed/17118126
all: That 3-day vs 6-month gap also suggests that the hplc-based plasma concentration tests may not be all that informative, even if they were more readily available. What one would really like to measure is the amount of rbv in cells and, for now, hgb drop may be the best scale, crude as it is. The take-home message seems to be that if one's hgb drop is closer to 1.5 than to 4 there *may* be grounds to increase the dose...
Maybe they just naturally produce more bile or some other digestive enzyme helping the Riba absorb for which the fat is merely the stimulant???
One would also think intestinal flora, it's health and the general permiability of the intestines would have some effect.
In any case, I'd want some actual data as to WHY Lindahl thinks it makes no difference.
We do know that fat aides digestion, and that fiber tends to bind other things up right??
Well, based on my side effects and blood work both my Riba absorption took a leap when I included fat AND excluded fiber from my dosing times.
While I would be more likely to conclude the elimination f fiber had more to do with my absorption rate, it doesn't rule in or out the role of fat/bile and there are more than a few studies on pubmed noting as much as a 1.5 increase in absoption with fat.
(I think that mean one and a half times greater absorption not 1.5 percent, someone correct me if this is wrong please).
I admire the work K Lindahl has done on Riba absorption, it's a key to SVR and should be monitored through blood work to obtain optimal results for all, but I'd still wonder, if she hasn't done any double blinds herself, then upon what does she base her cynism here. I assume she has some rational. ????
pros: keeping up on your blood lets you know you are making progress, if you are
cons: now reverse that if your results aren't primo.
in the end, it can make you crazy, thing is, they say insurance wants to cut you off at 12 weeks if you don't get a 2 log drop
but that is NOT ALWAYS TRUE. Mine didn't, and was fine with me going out 6 months to get that 2 log drop....
(which means all that fear of being cut off is being put on people unnessessarily, and God knows how good that is NOT to our mental states)...
While ins may not be basing it on 12 week results. Since the VL moves around a LOT, especially if you have other illnesses as I did...then you can be discouraged when you really may not be down for the count.
PS, my doc is a statistical nut.....I had to pitch a fit and quote 50 studies to NOT become another....tombstone. Being treated as an individual, regardless of whether you have a 90 percent chance or a 10 percent chance, is still our right in this country...for how much longer is seriously in doubt...but for now it is....but you must assert your rights.
For myself, I decided to go along with the doc on waiting from month 4 to month 6 on the PCR (not the CBC's) mainly because I had made up my mind to go the distance and not give up prematurely because there are exceptions to every rule.At first I did not see his point, as he did not give me ANY rational...but later I reasoned.... If 2 out of 10 people clear late, then that's 2 out of ten that would be sick and die, because they let a doc, insurance company, or blood test make them quit.
Likewise if I tie myself up in knots at 4 1/2 5 5 1/2 months...what good will that do??
the question becomes one of statistics vs. sanity. Even if your VL goes back up for a while, do you automatically want to quit? Once you resolve whether to follow statistics or your own resolve it will get easier.
In either case, I think some monitor too much, and other's not enough.
think of it like a war, which it is. One day on the battlefield, the bad guys may win 2 to 1...but the next day you may win 3-1. In the end, it's your life that's at stake so how do you not just keep up the battle until there's no one left standing to fight?
If you were a soldier on a blody battlefield, you'd want to go home every day, as you are experiencing the carnage right? Unless you can look past all the blood, and keep the goal, and what is at stake clearly in mind. So that's what I'm doing, not looking at the blood or set backs, so to speak, looking at the hill upon which I intend to stand and plant a victory flag.
hope you find peace with this.
maryB
haven't gotten thru all this as have to get off line awhile but....
Flguy.......Another aspect could be a person who wants to evaluate tx response and make an early decision to continue or not..........
I have had VL results from starting day to 2 weeks, 4 weeks and on. I have needed these in my changes, decisions thru out.Without reading all......I believe starting VL and 2, 4, and so on is important in tx. And the sensitive testing.
Re-read all later, but as some said......you should be able to ask for it, NOT unreasonable request.
LL
Next I go to the lab. Now it gets weirder and harder. All they understand is that HCV tests are covered by the government and that they go to the health unit. I keep trying to tell them that it's not covered and I want to PAY for it. They don't know how to deal with out of the box requests. I get given the number for their main lab and the Health Unit.
I called the Health Unit today and talked to their HCV "point person". She tells me that the labs only DRAW the blood, not test it. That the blood actually gets tested at Public Health LABS. So THAT is what they meant by "it" goes to to Public Health.. the BLOOD does.
So the Public Health nurse gives me the number for the Lab next...I called around 4pm and the young woman told me to call again on Tuesday (Monday is a stat holiday in Ontario) when everybody would be back and they'd help me wade through my request and see what can be done.
Step by step. I'll see how it goes.
http://www.medscape.com/viewarticle/416602_3
Good article. Thanks again.
Trish
" Although a standard meal did not affect ribavirin bioavailability (F1), administration of ribavirin with a high-fat meal increased bioavailability by 46% relative to the fasting state. A high-fat meal prolonged the duration of the zero-order input part of the absorption model, with D1 increasing from 0.498 h (fasting and standard meal) to 0.740 h"
It's worth researching this further, but some of the doubts about the merits of combining rbv with fat may have been settled over the past few years.
Also Trish, if you're really wiling to pay for your tests out of pocket you may be better off by simply having the local lab do the draw, keep the blood at -80 then ship it to the lab of your choice. One advantage of this is building up a library of blood samples should you want to go back and have one retested.
As for my tests. I wish it were that simple. I'm dealing with labs who don't do private testing for people. You'd think I could find one. I'm working on it. I'll be widening my search to the U.S. soon, simply so that I know what options are available.
The labs here are used to doing testing under government guidelines and protocols. What I'm asking for falls outside of that. So I walk in and say I want this done and I want to pay for it and they say "oh no...you don't have to pay for that, the government does." Then I launch into my spiel and I say that what I want is different than what the government pays for and how can I get this test done and pay for it myself? So far I've been met with blank stares and frustration on their part at such a seemingly simple question. They have a standard form to fill out for HCV PCR's and they have no procedure outside of that. The last place I went, she said " I don't KNOW how to give you what you want!" and I told her that's fine...but someone up above her must. And she gave me a couple of phone numbers to call. And I'm chipping my way through a system that operates on standard protocols when what I want is non-standard. The next phone call is to the lab that actually does the testing on the blood itself. And that happens to be the Public Health lab....as apparently I'm told not just any lab can do HCV RNA testing. And that's where it's done here. Argh. By the time I'm done...I'll have yet another educational experience under my belt.. but it's worth it because, well, of what I hope to accomplish in the bigger picture as a result and I'll leave it at that.
I'll keep in mind what you've said and pull it out as a stratagem if it fits within what they're willing to do. I just need to know how to pay for what I want and then get a process in place to be able to have me and others follow it.
jasper
"This study shows that in HCV genotype 1, treatment duration should be tailored to the 12-week on-treatment virologic response," Dr. Mangia and colleagues write. "HCV RNA should be monitored qualitatively at week 4 to identify patients with the highest likelihood of response, and at weeks 8 and 12 to determine if extended duration may be required," they conclude.
Individualized Treatment Duration for HCV Meets With Success
NEW YORK (Reuters Health) Jan 15 - In patients with hepatitis C virus (HCV), individualizing the duration of peginterferon/ribavirin treatment yields success rates similar to standard 48-week treatment, thus sparing unnecessary costs and side effects, according to results of two randomized controlled studies published in the January issue of Hepatology.
In one study, Dr. Alessandra Mangia from "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy, and colleagues treated 696 patients with HCV genotype 1 with peginterferon alfa-2a (180 g/week) or peginterferon alfa-2b (1.5 g/kg/week), plus ribavirin (1,000 to 1,200 mg/day). Patients were randomized to treatment for 48 weeks (the standard treatment group; n = 237) or for 24, 48 or 72 weeks if HCV-RNA was undetectable at 4, 8, or 12 weeks, respectively (the variable treatment group; n = 459).
According to the investigators, results showed "equivalent rates of lasting viral clearance after therapy administered for the standard 48-week length or a variable duration tailored on the first undetectable HCV RNA during the initial 12 weeks of therapy."
Nearly 49% of patients receiving variable treatment based on detectable HCV RNA achieved a sustained virologic response, compared with 45% of patients in the standard treatment group (p = 0.37), Dr. Mangia and colleagues report.
"This study shows that in HCV genotype 1, treatment duration should be tailored to the 12-week on-treatment virologic response," Dr. Mangia and colleagues write. "HCV RNA should be monitored qualitatively at week 4 to identify patients with the highest likelihood of response, and at weeks 8 and 12 to determine if extended duration may be required," they conclude.
Meanwhile, in a study of 428 patients with HCV genotype 2 or 3, researchers from Norway randomly assigned patients who achieved a virologic response after 4 weeks peginterferon alfa-2b (1.5 g/kg) weekly and ribavirin (800 to 1,400 mg/day) to complete either 14 weeks or 24 weeks of treatment.
In intention-to-treat analysis, Dr. Olav Dalgard from Ulleval University Hospital, Oslo and colleagues found that 81.1% of patients in the 14-week treatment arm and 90.7% in the 24-week arm achieved a sustained viral response.
Among patients with an HCV RNA test 24 weeks after the end of treatment, 86.3% of the 14-week treatment group and 93.2% of the 24-week treatment group had a sustained viral response.
"In conclusion, we cannot formally claim that 14 weeks treatment is non-inferior to 24 weeks treatment," Dr. Dalgard and colleagues write. "However, the sustained virologic response rate after 14 weeks treatment is high, and although longer treatment may give a slightly better sustained viral response rate, we believe considerable economical savings, good response to re-treatment, and less side effects make it rational to treat patients with genotype 2 or 3 and rapid viral response for only 14 weeks."
Hepatology 2008.
Glad you got the 'script', now hope you get it done!
I had a woman Dr. for years, loved her! She left and went to another office, they don't take my (crummy) insurance. I tried to see her and to pay CASH! They don't take CASH??? (self pay!) I said "okay, so if I had 20 million bucks and want to pay CASH for everything, I can't?" .....'No mam, we don't take cash, self pay'! I haven't been able to get past them just to talk to her! Sending her a letter as she will be amazed what has come of all the 'other' office's mistakes, and want her opinion on some things! She was the kind of Dr. that when she ordered a test for you and you didn't go, she'd call you herself and say "WHY haven't you done this? Get over there and do this!"
Pretty bad when cash doesn't work!
LL
"Ribavirin is rapidly absorbed following oral administration (mean time to maximum concentration [Tmax] = 1.5 hours), followed by rapid distribution and prolonged elimination phases (single-dose half-lives of absorption, distribution, and elimination are 0.05, 3.73, and 79 hours, respectively)."
I find the differentiation in the article between duration of half-life for single dose and multiple dosing interesting: 79 hours vs 298 hours. 298 hours equals 12 days and 10 hours. (Kcmike mentioned a half life of 21 days in another thread. Was that incorrect?) 298 hours would explain why many seem to be feeling better 2 weeks post tx.
Notice also the mention of approximately 4 weeks to reach steady-state ribavirin concentration. In other contexts here on Medhelp 5 months have been mentioned. Which is correct?
And lastly notice the mention of approximately 15 half-lives (6 months) to ensure no effect on fetus.
"During multiple dosing, ribavirin accumulates extensively in plasma, with a ratio of multiple-dose to single-dose AUC at 12 hours (AUC12hr) of 6.[17] Following dosing with 600 mg twice daily, steady-state ribavirin concentration was reached by approximately 4 weeks, with mean steady-state plasma concentrations of 2,200 ng/mL. After discontinuation of dosing there was a washout half-life of 298 hours.[17] The extended washout period likely reflects slow elimination from nonplasma compartments (Figure 5). The fact that the multiple-dose ribavirin half-life (298 hours) is considerably longer than the single-dose half-life (79 hours) means that it is not possible to predict (ie, model) multiple-dose ribavirin pharmacokinetic parameters based on single-dose parameters."
"The extensive accumulation of ribavirin nucleotides and their slow dephosphorylation contribute to the long half-life following multiple dosing (approximately 300 hours). To prevent potential teratogenic effects, we have estimated that 6 months (approximately 15 half-lives) is required to ensure a complete washout following cessation of dosing."
jasper
jasper
jasper
.5 hour to dissolve because of outer coating
1 .5 hours to work it way into digestive system
3 hours to reach total absorption and distribution in blood plasma depending
on person variable 3 or 4 hours but I used the 3 hours in the equation.
5 hours total x2 = 10 hour front end and back end
168 hours from intake to elimination
-10 5 front end and 5 back end
158 divided by 2 = 79
Jasper
That Preston'99 paper cited as reference 79 in Lindal's dissertation,
http://www.ncbi.nlm.nih.gov/pubmed/10508023
sets out the nine differential equations they used to model rbv's flow through the body. As you posted earlier, the term "half life" applies to any phenomenon where some quantity decreases with tiime, so as rbv moves from compartment to compartment through the body, the term half-life applies to any compartment that rbv is diffusing out of, not just final elimination.
The quality of any model comes down to how realistically it describes what's really happening. Even with 9 ordinary differential equations (ODEs) the Preston model is a simple-minded, three compartment, description of how a single rbv dose breaks down and as emphasized by that 79 vs 298 difference doesn't do a good job of describing the "multi-dose" regimen on tx (there likely are more sophisticated models out there that handle multiple dosing; this is probably the sort of stuff pharmacology students are tortured with).
The 4-week to steady state claim seems long and may be another area where that review is a bit dated (since it came out shortly after rbv was fda-approved for hcv in '98 it probably uses many of the same studies submitted for fda approval and that are now part of the med insert fine-print). There's a good graph of plasma concentration at start of tx with std rbv dosage in various patients in Figure 1 of
http://www.ncbi.nlm.nih.gov/pubmed/17494069
things look pretty stable after 14 days.
1 .5 hours to work it way into digestive system
3 hours to reach total absorption and distribution in blood plasma depending
on person variable 3 or 4 hours but I used the 3 hours in the equation.
5 hours total x2 = 10 hour front end and back end
168 hours from intake to elimination
-10 5 front end and 5 back end
158 divided by 2 = 79
---------------------------------------------------
It appears that the most important PharmaKinetics of ribavirin have been omitted.
2 days until you need sleep aids. (16 divided by 8 hours sleep)
4 days until you need an AD. (20 divided by 5 days of week)
7 days until you need a divorce (70 divided by the average number fights per hour (10))
I am stunned. They consider anything above 800,000IU/ml to be "treatable" so that is why my doctor said that I'm already at 1.3mil IU/ml so it doesn't matter. However...it still matters to ME. I simply understand now what he said when he said...there isn't anything higher.
I'm just going to take awhile to digest that. Whether I get in the drug trial or not determines how far I take this and in what direction....but...wow. I guess to some you'll be saying "what's the big deal?" but...I don't know...an accurate baseline seems really important to me.