Is RVR the same with a PI in the mix?

[Andiamo1]

In the thread where I posted my PCR results, dointime suggested the RVR MIGHT not mean the same thing (as a predictor of SVR) when a protease inhibitor is part of the therapy.

From conversations I had with researchers, I believe it is the same, but no empirical data exists to prove it conclusively.  You can infer from my test results that Telaprevir eliminated the wild virus within a week and infn/riba eliminated (below the assay) the mutations over the next two weeks.

What do you all think?

[Andiamo1]

Please don't interpret this as me looking for a reason to opt out of the rest of the trial.  I have decided that I will do my best to stick it out as long as I can tolerate it.  The reason for the post is my desire to understand the meaning of the results - nothing more.

[jmjm530]

Preliminary SVR data suggests it's the same, but an excellent question I wondered about from the beginning. In fact, I questioned my own RVR for similar reasons since I double-dosed and did high-dose riba instead of SOC which much of the RVR data is based on. But again, RVR in these situations as well does seem to translate into SVR, both for me and in other studies such as later double-dose studies, if I'm not mistaken. Another good question might be is Telaprevir SVR as durable as SOC SVR, since it hasn't been around long enough to test. Again, we can only extrapolate, but I see no reason it shouldn't be, and in fact -- some of the "occult" nuts (I use this endearling) here might suggest you will end up with a better type of SVR, although I'll happily take SOC SVR, or as my doc calls it, being cured.

Be well,

-- Jim

[mremeet]

I see no reason for it be different considering what we've seen so far from 24 week participants and the odd story of a few people who had to discontinue very early (as early as week 4) because of rash etc and still managed to SVR. And it's funny what jim said about another possible flipside of a VX born SVR compared to an SOC SVR: "...and in fact -- some of the "occult" nuts (I use this endearling) here might suggest you will end up with a better type of SVR..."  I've secretly wondered this myself, although thinking it's just too silly to believe it might be true. But one thing I've anecdotally noticed so far is that just about every single VX950 SVR I speak to, they just seem to be happy as clams. I don't recall seeing any of them (as they move away from treatment) speak of excessive long term sides, or having a long recovery, or any of the things that I've heard about frequently with SOC after treatment is over. And based on how I've been feeling, I just wonder back in the darkest anecdotal corner of my mind: Does VX950+SOC impart a "betterer" and more thorough cleansing of the virus? Is it possible that if this whole occult/low level thing is really legit, and there is some kind of constant low level immune response that makes people feel crappy, then maybe VX950+SOC really cleans it ALL out so there's absolutely NO virus left, and therefore no grinding low level immune response??

And then I just say NAHHHHHHHHHHHH. Sounds dumb, can't be true. But??????????  ;-)

[desrt]

If the results of any of the other protease inhibitor trials are any indication, no - the RVR is meaningless. Everyone gets it including those who relapse immediately. Here's hoping VX is different.

[Andiamo1]

The other trials have all been phase 1 short duration and never expected to produce SVR.

My question relates to probability of SVR with 24 or 48 weeks of treatment.

[Andiamo1]

I meant to also ask about RVR after a previous failure of treatment; does it mean the same in this case?

[mremeet]

What are you talking about by saying it's "meaningless?" I think you're confusing the early phase of testing where patients only received short term PI monotherapy with no IFN or riba. In those situations the RVR is meaningless as far as the ability to attain an SVR at the conclusion of testing.

[Ironduke]

I had this conversation with my Hepatologist this past week.  I am in week 24 of SOC + SCH503034 and have been UND since week 2.  I am in the 48 week arm of the study and asked if continuing for another 24 weeks would do more potential harm than good, based on studies that show relatively equivalent SVR rates for 24 and 48 week treatment of patients who achieved RVR.  His answer was that the the mechanism that produces the steep viral decline using the PI is different and they really don't know for sure.  One reason for the trial, I suppose.  

[dointime]

Here's my take on this.  The reason RVR predicts SVR using only SOC drugs is that the rapid clearance of the virus from the blood indicates that YOUR virus in YOUR body is highly sensitive to the SOC drugs.  From that it has been found by studies that you can extrapolate out for the duration and assume that clearance of the virus from the body tissues using the same drugs will be equally as fast and effective.

Now lets say we are talking about the 12 x 12 triple therapy with telaprevir.  Suppose telaprevir clears the wild type virus to UND in 2 weeks but there are still resistant mutations left hanging around for the 12 weeks below the level of detection.  You cannot extrapolate anything about how those mutations will behave in the 2nd 12 weeks under SOC alone because you are using a different drug cocktail.    

So bottom line, I don't see how RVR as a predictor of SVR can be meaningful  if the drugs used are switched part way through tx.  

In your case the drug cocktail did eliminate all of the virus below the assay over the first 3 weeks, and that's obviously a great result for you.  And you've stayed UND since then, which is even better.  The hope is that the triple therapy hit the virus so fast that it knocked it out totally before it had a chance to establish viable resistance and you get your SVR.  

That's the action of the viral kinetics of telaprevir though, and can't be confused with using RVR as a predictor of SVR in cases where resistant mutations persist below the radar even after telaprevir is discontinued.

Gawd, if only they had a test which could tell us when ALL the virus was gone!

dointime.    



dointime  






        

[Andiamo1]

I am curious about what you think after you read the abstracts posted by Jim.  I think that they disagree with what you are guessing, but I have so much brain fog these days, that I am not sure what I think any longer.

[dointime]

This page from clinicalcare talks about the predictive value of RVR needing to be reevaluated for the PI's.

http://clinicaloptions.com/Hepatitis/Treatment%20Updates/Small%20Molecule%20HCV%20Agents/Modules/Chung/Pages/Page%2011.aspx

"On-treatment viral kinetics will likely continue to be helpful predictive tools, but their role is necessarily expected to shift with addition of STAT-C agents. For instance, NS3/4A and NS5B inhibitors should be associated with high rates of Week 4 rapid viral response and Week 12 early virologic response by virtue of their action as direct antiviral agents. What remains to be seen, however, is whether the achievement of earlier viral clearance will translate to improved SVR rates for patients receiving peginterferon alfa plus ribavirin for a shorter duration than standard of care. In other words, the predictive value of rapid viral response and early virologic response achievement with STAT-C regimens will likely require re-evaluation, since a rapid kinetic decline achieved with a directly acting antiviral agent may not equate to the rapid decline achieved with peginterferon alfa and ribavirin. The results of upcoming phase II studies of add-on treatment to standard of care will be instructive in this regard."

[dointime]

What abstracts posted by Jim do you mean Eric?  Is there another thread on this.  Could you post the link please?    
dt.

[Andiamo1]

Jim posted the abstracts the Vertex will present at the AASLD

http://www.medhelp.org/posts/show/322425

[dointime]

Andiamo you wrote:
"I have too much brain fog to trust my conclusions, but I did conclude from two abstracts, that the percentage of people that reach undetectable by week 4 is the same percentage that reaches SVR.
Did you conclude that as well or am I suffering too much from brain fatigue to process all the data?"

I have to say that I did not read anything in those abstracts which demonstrates that RVR with telaprevir predicts SVR with about 90% certainty, as is the case currently with SOC alone.  

Sorry, I know that's not the answer you want to hear.  If I missed something then please let me know.  We're all learning as we go and I need to be fully primed with all the info for my next round.

dt.        

[mremeet]

HEY! You're the first person here I've seen that is in the SCH503034 trial!! Wazzzup dude!?? Welcome aboard, you're a rare bird indeed. So what's this you say about you going UND at week 2?? That's awesome man, congrats! Can you give us any more info about your experience in the SCH503034 trial? Know anybody else in the trial you'd like to bring aboard?  Would REALLY like to hear more about this drug and how it's been working out for you. In fact you should start a new thread dedicated to SCH503034 and what you've experienced with it so far. There are some folks here who are in bad situations, where they have failed treatment with VX950 (because of no riba) or with cirrhosis and not much time left...they need some info on anything new and promising that may be coming on soon. So please fill us in on what's happening with the SCH503034 trial (what an awkward name though!).

Oh yeah, you said above "...asked if continuing for another 24 weeks would do more potential harm than good, based on studies that show relatively equivalent SVR rates for 24 and 48 week treatment of patients who achieved RVR.  His answer was that the the mechanism that produces the steep viral decline using the PI is different and they really don't know for sure."  Well, yeah maybe they don't know for sure, but it's a pretty safe bet (especially with what happened to the VX950 24 week group). Let me give you a tip: the *real* reason he's saying that is so you will not discontinue early and drop out before your assigned treatment duration. That would screw up their data, and it might screw up the amount of compensation he'll be receiving from Schering Plough too. Not that I'm suggesting you should drop out early, but take what he said with a big fat grain of salt is all.

[jmjm530]

Duke:  His answer was that the the mechanism that produces the steep viral decline using the PI is different and they really don't know for sure.  
---------------------------------------
Of course your doctor is correct and like you said, that's why it's a trial -- and frankly, what else could he say given his position as a trial coordinator? However, like "Mre" says, the magic number for Telaprevir appears to be "24" and not "48".

All the best and yes, being UND at week 2 is awesome.

-- Jim

[Andiamo1]

Sorry dointinme, but I disagree once again.  One paper had the RVR rate at 80% and the other had the SVR rate at 80%.  Sounds like a good predictor to me!

I re-read some of the papers and it seems to me that if you achieve RVR by week 4 and don't have a breakthrough by week 24 you have a very high probability of SVR.  I am to foggy to do the exact math, but it seems to me that if you fall into the above catagory you have a better than 90% chance of SVR.  

I only wish I could get my head clear enough to put the numbers into a spreadsheet. But that will have to wait until I am off treatment!

[Andiamo1]

[GoofyDad]

Andiamo -

I haven't read any of the papers under discussion. But looking at this quote "One paper had the RVR rate at 80% and the other had the SVR rate at 80%.  Sounds like a good predictor to me!"  - At face value - there's no proven correlation between RVR and SVR. It could theoretically be true that 100% of the non-RVRs reached SVR, making non-RVR a compelling predictor for SVR.

Using a less extreme example, lets say 100 pts in study. 80 reach RVR - 20 do not. Possible that 74 RVRs make SVR and 16 SVRs, for a total SVR rate of 80%. In that case the RVR event has no bearing on SVR whatsoever - 80% of either group make SVR.  

[Andiamo1]

All of  these studies use probability as the predictor.  You could flip a coin 2000 times and always get heads.  Does that mean anything?  The more you flip, the more likely you will average 50%, but there is nothing to stop you from flipping 1,000,000 times and always getting heads.

In the normal world, if  a large group gets RVR at 80% and another large group SVR at 80%, it becomes likely, but not definite, that RVR predicts SVR.  It is not guaranteed that it will happen, just more likely.  Even if all the people are in the same study, not all RVR will reach SVR and even if they all do, there is still uncertainty because of the coin flip problem.

So until we have a cause and effect established, we will only have probability to deal with.  It is better than nothing, but far from perfect.

It seem logical to me that that the major variables are our bodies ability to deliver the drugs to the virus (absorption and delivery),  the type of variant virus and the efficiency of our immune system.  Vertex is measuring these things now and hopefully, someday we will have more definitive ways of measuring the direct variables involves with SVR.

[Andiamo1]

After a few hours more sleep, it seems like I should add to the above post.

First, it certainly is far more accurate to have the same group of people followed from RVR through SVR and I didn't mean to imply otherwise.  That said, accurate is a relative term, not absolute and using to groups to infer something does provide insight into the usefulness of RVR with Telaprevir.

I think we all agree that RVR is a good predictor with SOC and the reason for this is that is also is based on the same factors that produce SVR: those I mentioned in my earlier post and I am sure plenty that I am aware of.  So if we have to measurements of the same data with one available before the other, we can say one is a predictor of the other.

So we have two studies of two groups.  All the people in both groups have HCV.  I ask the following questions:

If 0% in group A achieve RVR and 80% in group B achieve SVR is it more likely that RVR is a predictor of SVR?

If 100% of group A achieve RVR and 80% of group B achieve SVR is it more likely that RVR is a predictor?

If 80% of group A achieve RVR and 80% of group B achieve SVR is it more likely that RVR is a predictor?  Since this is the case, I think taking all the data about RVR into consideration, I think it is likely that RVR is as good a predictor with Telaprevir as it is with SOC.

Eric

[Andiamo1]

Sorry for all the typos in the above post.  I guess 4 hours total sleep is still not enough - LOL.

[Ironduke]

Totally agree with you that the trial coordinator has a vested interest in me sticking with the trail.  I had no expectations he would recommend that I stop treatment.  I think he was honest, though, in his belief that it is uncharted territory as far as this particular combination of drugs is concerned, so he is not going to suggest I drop out unless I had severe problems with sx.  I also agree that preliminary data from VX950 trials looks promising, so I am very optimistic about my chances for SVR.

I haven't heard much either from others who are in this trial.  The amount of information out there is really limited.  I know our study coordinator has only 2 other patients, one also became UND somewhere between day 1 and day 14, I am not sure about the other.  My experience has been about typical for SOC - the first 12 weeks were pretty hard with anemia and nausea being the worst sx.  Thanks to procrit I am doing much better and tolerating things pretty well.  It is hard to say for sure, but I don't think any of the sx are due to the investigational drug.  I have a mild rash but I think that is due to the riba.  All in all, based on my limited experience, this drug is showing real promise.  I will be sure to keep you updated on my progress.  

[mremeet]

Thanks for the response. What is the duration of your SCH503034 dosing? In the Prove 1 VX950 trial it was 12 weeks, just wondering what length of treatment they're using for SCH503034. Also you mention procrit...were you allowed to take procrit during the period of time you were taking SCH503034? Glad to hear things are going so well for you. I'd say your odds of SVR are excellent, good luck.

[Willy50]

A few notions;

Desrt; " the RVR is meaningless. Everyone gets it including those who relapse immediately."

I'm not sure this is correct.  Yes, most TVR responders DO RVR.  I think I
heard that all but one viral breakthru was within 4 weeks.  A nearly double SVR rate may end up accompanying the great RVR data.  Are they linked; almost certainly.  I don't know if anyone has spoken about the ultra responders who clear in a few days or within a week.  Should those folks be in a whole new category of responders who can treat for even shorter durations? (shorter than on a 12&12)

It's true that the idea has not specifically been tested on PI's or on Vertex but I believe that the data coming in will show that there will be a curve with response which corresponds to cure.  IF the response rate is too slow the virus can mutate around the treatment in many (but not all) cases.  Also keep in mind that an ultra sensitive PCR can still leave a tremendous amount of HCV RNA in a persons blood or tissue even though it comes back as "undetectable".  

Whatever the treatment, whether SOC or SOC with TVR or some new cocktail concoction the mechanisms of immune response remain the same, as does viral replication of HCV.  You can change the drugs but the host and virus remain largely the same.   The same mechanisms for responding and maintaining an SVR may be quite similar in both SOC and SOC with TVR. I think the mutations could be a wild card in the mix where a relatively few resistant virii remain and although an RVR is attained it is not durable.  

We can hope that a full dosage regimen (with rescue drugs if needed) may help the ultimate SVR rate.  We may also see that the inclusion of another drug into the cocktail (whether SCH 503034 (boceprevir) or other new compounds in trials) could wipe outmore of those last remaining varients and provide a higher ultimate SVR rate.

I think for most people a slow response rate allows those variants to mutate around a treatment.  A fast and complete response may be the key to SVR. I believe that it will remain a key predictor for SVR.

Willy

[GoofyDad]

Not to keep flogging this horse - but given the info we are discussing - the only relationship I can see between RVR and SVR in VX is that inferred from what we know about SOC. The fact that there are two 80% numbers in the mix is a possible cause of confusion.

How about this -  80% of the people in the study were blonde. 80% of participants SVR'd.  There is no statistical relationship between blonde and SVR.

Maybe there is more data - again I have read the papers. Commonsense would certainly say that RVR improves one's odds. First clearing the virus at any point improves you above the 80%. Then RVR presumably improves the odds further. No breathrough improves the odds yet further, as does full compliance while on tx.

I don't mean to rain on your parade at all. I know you are preparing for a possibnly significant decision point - and so I want to share with you what I viewed as a flaw in the logic progression.

Take care and be well. It really looks like you have this one on the ropes. Soon you will close this final chapter in your history of treating Hepc.      

[Andiamo1]

You are not raining on my parade and if the relationship between hair color and SVR were as loose as RVR and SVR you would be right.    Luckily, that is not the case and there is a statistical relationship already established between the two.  We are only trying to see if it is similar when a PI is in the mix.  There is more evidence to suggest it is than evidence to suggest it is not.  The 80% similar results simply is more evidence to suggest that it is still directly related and not confusing at all.  Only empirical data will offer conclusive proof and we don't have that as yet.

Thanks for the good wishes.  I guess we have fleshed this out as far as possible without more data.

I have decided to stick it out as long as I can do it.  It gets harder the older I get, but I feel substantially better now that I am off Telaprevir.

[GoofyDad]

The 80% similar results simply is more evidence to suggest that it is still directly related and not confusing at all.

I don't see that connection. Glad that you do.   Best wishes.

[Andiamo1]

I am sure the only reason I defend this position is due to interferon.  I apologize for trying to defend an idea that has no scientific merit.  

While I don't agree with you completely, you are certainly right that any meaningful data must all come from the same study tracking individuals from RVR to SVR.

Eric

[jmjm530]

Is this a theoretical discussion and speculation or has someone seen the numbers that will answer the question? The numbers no doubt are there, either published or that probably will eventually be analyzed and published.

As to RVR and SVR with SOC, we do know that a strong relationship exists and there is no reason not to expect the same with Telaprevir. It may turn out, however, that RVR with Telaprevir is different from RVR with SOC. It may be UND at week 2 (or even 1) versus week 4. But I haven't really delved into it myself, so here I'm speculating.

That said, I have read that Telaprevir tx time could conceivable be brought down from 24 weeks to possibly even 12 in some individuals. I imagine the criteria used would be viral response, i.e. RVR, however that might be defined with Telaprevir.

-- Jim

[Andiamo1]

Purely theoretical with me taking the position that RVR is RVR no matter what is in the mix.  I have too much brain fog to put the numbers in a spreadsheet.  Unfortunately, the numbers that did jump out at me were in two different abstracts and I reluctantly admit that weakens them considerably when you compare RVR from one with SVR in the other.  I agree with you that the numbers are probably there but will take some effort to dig them out.

The papers do suggest that TPR hits the wild virus hard and eliminates it within the first two weeks.  After that, it is the job of ifn/riba to hit the mutants.  I guess that means you could make a case that the slope of the curve will be different, but I still maintain that early undetectable means the same thing with or without TPR.  Hopefully, I will have more information later today after I talk with the big guy.

[jmjm530]

I probably didn't make this clear in my last post, but I tend to side with you and think there most probably  is a relationship between RVR and SVR with Telaprevir. I just haven't looked at the data, and as stated, "RVR" may (or may not) need a different definition with the PIs.

-- Jim

[Andiamo1]

I met with the Capo Grande this morning and he said the following:

RVR is the same with or without a PI.
In my case, because of my age and the fact that I will not treat again, I should go the 48 weeks.

[Myown]

If RVR for geno 1 is "UND by week 4",,,,,how can RVR for geno 2 also be "UND week 4"? Since geno 1 is the hang tough geno and geno 2 'the easy one,' how could doctors consider RVR at 4 week for both? Geno 2 should be UND at week 2 to be considered RVR IMO. Maybe I'm off base, but this just came to my mind and wanted to see if there was an answer.

[jmjm530]

My understanding is that RVR means UND at week 4, regardless of genotype. The question really isn't what is RVR but what is the *significance* of RVR between the two genotypes -- or between different drugs for example.  And like you suggest, RVR seems to have different implications with geno 1's than with geno's 2.

[Myown]

My understanding is that RVR means UND at week 4, regardless of genotype
----------------------------------------------------------------------------
Yes that's my understanding also, BUT it doesn't make sense if you really think about it IMO. If both people are on SOC, and one person is a geno 1 and is RVR at week 4 and the geno 2 is also UND at week 4 (and not before).....this tells me that the person who is geno 2 has a few tough virons. It makes no sense why they have both on equal ground.

[jmjm530]

I agree with what you say but don't think they give the two different RVRs (geno 1 and 2) equal weights. Or at least they shouldn't. Not really that versed on geno 2's, but with a geno 1, an RVR means "yippidee doo" and with some people a choice to treat only 24 weeks. With geno 2's, on the other hand, RVR is sort of expected, and if you don't get one, then probably have to treat longer than 24 weeks. I think. Again, not as up on geno 2 protocols as with geno 1's.

-- Jim

[Myown]

Yeah but ya know what Jim it has nothing to do with knowing protocols. You know alot
more than I do and this is crazy when I think about it, RVR for Geno 1 is great at 4 weeks cause its a strong virus,,,BUT my geno 2 is supposed to be 'weaker,' BUT if it takes JUST AS LONG AS GENO 1 for RVR, it doesn't look that WEAK to me. I know I am repeating myself,,but this is so plain a clear to see and I didn't see it before -ever - and it hit me today. I will bring this up at my appointment.
Thanks for your reply.

[jmjm530]

I think we're in agreement and I'm sure your doc is too. I think the justified optimism you and your treatment team shared was not solely because you were RVR, but because you had what is statistically an easy-to-treat genotype AND you RVRd, which meant the drugs were working as *expected* -- as opposed to working as *hoped* in the case of let's say a geno 1. At some point in the future, more predictive "RVR" points may be developed for geno 2's (such as the two weeks you mentioned) that will give them more significance in genotypes other than 1.

In fact, even with geno 1's, I have no doubt that better predictions could be made if more studies were done with earlier testing (weeks 1 and 2 for example) and then correlated with SVR. I believe some were done but not enough. And then again, this would require testing patients starting at week 1, which only a few of us got. Hard enough to get some doctors to even test at week 4.

-- Jim

[PSP-n-Me]

my team told me that RVR is RVR no matter what GT and the 4 week rule applies - the only difference in the GT is when you go for shortened tx based on GT and RVR - For instance the Liver Clinic I go to will shorten tx as such; GT 1 RVR tx time 24 weeks GT 2 and 3 RVR tx time 12 weeks

Hope this helps *dip*

[Myown]

Jim, I'm not just talking about ME as a geno 2 and 'justified optimism".... no one is in agreement with me cause if they were, I would have read this in a study and none of us geno 2's would be told RVR = UND at week 4. Possibly they will say I have a point, but .... If they 'agreed' with me then THEY should have been the ones who said ."well you RVR'd BUT for geno 2's it really should be at week 2, but you're looking good just the same. Believe me, since all the studies say RVR week 4 - we are a one size fits all and this is one of the reasons for relapse for some. For some reason doctors are not looking at this this way. Well I always say alot of our doctors don't have logic, they are book smart - no doubt, but logic is not always there.

PSP, thanks but I think I am having trouble getting my point across. Re- read my posts and maybe you will understand what I mean. I've never been that great at getting my point across.

[PSP-n-Me]

oh I completely understand your point - but in the eyes of the clinic I go they claim RVR is a 4 week test to determine if you are a rapid responder no matter what GT and what they do with that info is a deciding factor in what course of tx they do.- maybe most of them don't want to do a 2 week PCR (with SOC, not talking trials here) and that's why it is said the RVR 4 week rule applies to all GT's, don't know, but it's a good question...

[jmjm530]

Week 4 is RVR because that is the point that has been studied in trials. All subsequent "rules" such as shortening or lengthening tx, follow from that data.

Whether or not this is an optimum reference point for all genotypes is another matter. Probably it isn't and maybe newer trials will study different UND points such as week 2 or even earlier, for both genotypes.

Why they didn't study viral load at points earlier than week 4 for genotype 2's and 3's I don't I don't know. I think they should have for all the reasons you gave. Let us know what your doctor says on this matter.

All the best,

-- Jim

[glucklich]

I really don't have a clue, but I would think that RVR is only as advertises- UND at week 4. The desire here is to give meaning to having achieved RVR. That seems difficult at best without an understanding of the mechanisms of the drugs involved and the model of disease population used to give context to vital loads. Most models I have seen have both a Kill factor and a replication factor in them.These are perhaps different for different GTs. I also suspect he Kill factor depends on the individual as well.
The numbers I have seen are just the ratios of SVR(who RVR's)/RVR. I may have missed it, but I do not recall seeing a confidence number as well.If I am correct, then there is no statistical significance being asserted.
In any event with out the context of a model I think it is difficult to make inferences or predictions.

[Myown]

Why they didn't study viral load at points earlier than week 4 for genotype 2's and 3's I don't I don't know.
----------------------------------------------------------------------------------------------------------------------------------
Jim plain and simple,,,NO logic. Most of them just don't have it for some reason and I'm not just saying this because of what we are discussing today but there are alot of things that make no sense IMO with what they say. Here's just 2 examples that come to mind.....

1.. don't let your spouse use your toothbrush YET,,they say its safe to breast feed, BUT,, of course if your nipples crack ,quickly throw the child to the ground to prevent infecting her.LOL Well of course they don't really say quickly throw the child to the ground, but I think you get my point....what are women supposed to do if all of a sudden they "see"  blood on their nipple?AND,, only the blood particle on the tooth brush is dangerous and not the nipple?? Now of course we don't have to "see" blood for it to be there, so again.... where's the logic..

2. homosexuals are at high risk for contracting HCV during sex - not heterosexuals....oh, I guess the reason is gays have the 'good sex' and don't just lie there like road- kill the way married women do. LOL

So thats the story.
I'll let ya know. I will be seeing the doc soon.

[PSP-n-Me]

LMAO you'r a trip girl!  

[Myown]

hey I'm gonna hang with you more...its nice to have someone that likes me for me.

[Myown]

Nobody loves me but my moma and she could be jiving me too...BB King
My theme song LOL

[PSP-n-Me]

awww I wuv's ya even though you're a PITA  hehehehe c'mere and give the dip a hug LOL

[Myown]

hey thankyah sweety. My hubby got used to me being a PITA - you will too, some come on putcha arms around me and squeeeeeeeeeeze. ha!
seeya later.

[PSP-n-Me]

okay dollface - have a great night :)

[GoofyDad]

Andiamo. No worries my friend. Thanks for your graciousness.  

On RVR for diff genotypes - my sense is it's pretty much the same - RVR means something in the 24 week range - non-RVR means something in the 48 week range, regarless of GT. I think it's probably a little different because of crudenesss in the measuring stick. I'd venture that of RVR's the GT2 RVR's probably cleared on avaerage earlier than the GT1's - and similarly of the non-RVRs, the GT1s will probably on average clear later than the GT2's. So if we tested weekly, or semi-weekly, I think it quite probable that it would be the viral decline slope that mattered - not the genotype.    

[zazza]

Geno 2 and 3 RVR = 90% SVR  (2 out of 3 attain RVR)
Geno 2 and 3 no RVR = 50% SVR  (1 out of 3 do not attain RVR)

Geno 1 RVR = 90% SVR  (1 out of 5 attain RVR)
Geno 1 EVR = 70-80% SVR  (2 out of 5 attain EVR)
Geno 1 slow responders = 20-30% SVR  (1 out of 5 are slow responders)

To me a geno 2 or 3 with an RVR (week 4) is more similar to a geno 1 with an EVR (week 12). Actually I would be reluctant to call an UND week 4 a rapid response for geno 2 and 3. I agree with you here.

A geno 2 or 3 who is not UND by week 4 is a slow responder, and needs to consider extension and/or dose increase.
A geno 1 who is not UND by week 12 is a slow responder, and needs to consider extension and/or dose increase.

I think you are making a very interesting point here. If one is a slow responder as of week 5 as a geno 2 or 3, how can one be a rapid responder up to this very day?

[Myown]

Thanks, yup it makes so much sense. I don't know why I never thought of this before this morning.And thanks for the chart btw

I mean, yes there are so many other things to take into consideration as we all know - stage/grade etc. In my case 2b ("RVR" < according to 'their rules' , not mine after today) BUT I had a high VL to start with 8 million plus,,,but here's the interesting thing or at least interesting to me,,,,,when I was first dx my VL was over 10 million,,,now think of it,,,yes the VL fluctuates and yes it went down to 8 million BEFORE tx started,,so my immune system was controlling the other 2 million??? It wasn't  KILLED OFF cause I wasn't on tx,, so where are these virons go when our VL fluctuates? I don't know,,,BUT its NOT in the SERUM,,,so is it in the TISSUE?? I really don't know, and I have always wondered but I have a feeling that is where it goes (maybe I am wrong) BUT if I am right, in order to 'reach ' ALL that were in hiding, a longer tx may have done the job cause maybe my immune system was too weak after tx to control these others that it didn't or couldn't get to.... Again, I have no idea what I am talking about.Just guessing at this stuff.

One of the things that has led me down this path of thinking this way is that when you get hormones tested, the blood test show of course whats in the serum and a saliva test will show 'tissue level.'   Tissue level and blood level is never the same ..AND scientists have said that HCV is found in saliva when the VL is high. To tell you the truth, I think they should test saliva when we are on tx in addition to blood - at least at end of tx.

But anyhow, nice talking to ya.  Thanks again.

[GoofyDad]

I meant to add in my prev comments that I think at a minimum testing should be advanced for GT 2/3 so that the group gets split in half - zazza says 2-out-of-3, and I've also seen reports as high as 80% or more RVR. Being in the 80% club doesn't say a whole lot. So, it would make sense to me that if you were to test ealy enough to catch say the 20% of earliest responders - they would be candidates for shorter treatment. It's insane when you think about all the costs of SOC, both monitary and other, that more emphasis isn't put on accelerated treatments for the earlier responders. Yeah a TMA is expensive, but less than other aspects of TX that could be cut for a significant population - I suspect.  

As for fluctuation between 8 mil and 10 mil - I think its pretty insignificant. If I recall correctly - the tests can vary that much given blood from the same draw. In any event, levels fluctuate quite a bit I think, kinda a natural ebb and flow.  

[Andiamo1]

I met with Dr D to go over my test results and he seemed to feel that RVR is always a good thing regardless of a PI in the mix, but had to be interpreted based on the patients probability of SVR determined by factors such as age.  He said that the immune system ages as does all the major parts of our bodies and becomes less effective as we get older.

In my case, he felt that my age suggested that I would be safer treating for 48 weeks even though I experienced RVR.

[jmjm530]

Andiamo,

I was told similar (58 at the time) by my treating doctor, however two other liver specialists suggested that my RVR trumped age.

One difference, however, is that I was treatment naive while you did not respond previously. The other is that I was more or less SOC, while you're on a trial drug.  Plus you mentioned that this may be your last treatment. So all told, going for 48 make sense if you can tolerate it. Two age-related studies below. Wish they broke them down in terms of RVR versus non-RVR.

http://www.natap.org/2006/AASLD/AASLD_49.htm
http://www.natap.org/2005/EASL/easl_5.htm

[Andiamo1]

Thanks for the post of the papers.  Yes, too bad they didn't include RVR data.

The one thing I am sure of re: age, the older you are, the more difficult the SX are.  I do think I can hang in there for another 21 weeks.  At least I will try.  Procrit would sure make life easier!

[jmjm530]

They can't give you Procrit even at this point? I believe in following trial protocol and all that, but given your age, etc, you'd think things could be bent a little.

-- Jim

[Andiamo1]

So far, Vertex has disallowed procrit.  In the previous trial they did look the other way once people were off Telaprevir and just taking SOC drugs.  Perhaps the fact that Schering has now allowed procrit will put some pressure on them.  The SVR rates should improve if they allowed procrit instead of forcing people to drug reduce.

I know we don't agree on this, but I still believe it is a money issue and Vertex appears to be burning cash at a higher rate than predicted based on Q3 data.  My research coordinator says that rescue drugs have to be paid for by the company running the trial in order to keep a level playing field.  There are 400 people in prove 3, so allowing procrit would cost them a fair amount of money.

Eric

[jmjm530]

Let me ask you this. What happens to someone in your situation if anemia forces them to stop treatment either because of physical distress? Would the doctor just tell you to stop completely or would they take you out of the trial and treat you privatlely using Procrit? Just wondering what your options might be outside of the trial protocol?

-- Jim

[Andiamo1]

I did consider dropping out of the trial and going the route you suggest.  On medicare prescription drug insurance, that will cost me a lot of money, so I have tried to tough it out.  I would certainly do that if my only other options were to stop or drug reduce more than I thought was safe.

I am sure Dr D would go along with it, but I would have to make that choice without him, since he is involved in the trial and can't give me that advice without a conflict of interest.

Eric

[jmjm530]

Have you looked into the assistance programs from the drug manufacturer's? I know that Shearing and Roache have supplied drugs to some here based on income levels (as opposed to assets); and I believe there might be a similar program for Procrit. Also, wouldn't be surprised if you happen to be treating in a big hospital if they have an ample stash of both drugs. Both might be worth pursuing if you and your doctor came to the conclusion that remaining in the trial was not in your best medical interest. But like you say, you might have to initiate the discussion for reasons given.

-- Jiim

[jmjm530]

Given your age and the number of prior attempts, I think you might be able to make a good case for yourself. Your doctor seems very progressive and open.

[Andiamo1]

Thanks for the input.  I think I will give them a call and see what develops.

Eric

[Andiamo1]

It certainly looks like Vertex has answered the question with their latest data: RVR is still a predictor of SVR even with a PI in the mix.

Still an open quesition:  Is it a predictor of SVR with treatment experienced people?  I think the answer is yes, but probably a lower percentage of SVRs.

[merryBe]

>>>>>>>>>>>>"occult" nuts (I use this endearling) here might suggest you will end up with a better type of SVR..."  I've secretly wondered this myself, although thinking it's just too silly to believe it might be true. But one thing I've anecdotally noticed so far is that just about every single VX950 SVR I speak to, they just seem to be happy as clams. I don't recall seeing any of them (as they move away from treatment) speak of excessive long term sides, or having a long recovery, or any of the things that I've heard about frequently with SOC after treatment is over. And based on how I've been feeling, I just wonder back in the darkest anecdotal corner of my mind: Does VX950+SOC impart a "betterer" and more thorough cleansing of the virus? Is it possible that if this whole occult/low level thing is really legit, and there is some kind of constant low level immune response that makes people feel crappy, then maybe VX950+SOC really cleans it ALL out so there's absolutely NO virus left, and therefore no grinding low level immune response??

that's not an impossible theory, after all, before peniccillin, we threw sulfa etc at things and came close but no wipe out. so if this trio happens to be a better wipeout, than it is closer to the final penicillin for HCV. makes sense to me, though not an occultist.