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?

[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.

[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.

[Andiamo1]

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

Eric

[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.

[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

[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]

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]

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]

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]

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]

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]

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.

[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.  

[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.

[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?

[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.    

[PSP-n-Me]

okay dollface - have a great night :)

[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]

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

[Myown]

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

[Myown]

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

[PSP-n-Me]

LMAO you'r a trip girl!  

[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.

[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.