Digested the AASLD news, I am bummed too

[dointime]

Hepatitis researcher wrote in a previous post:
"Not only would Protease +SOC for clear nonresponders not permanently eliminate the virus but something much worse will likely happen ( to quote as mremeet has properly pointed out some hundred posts ago:  " you will be saddled forever with resistance mutations against this treatment component").: This archived resistance mutations against telaprevir would make it impossible to clear the virus at that important future moment  when finally the next chance to treat with an inhibitor combo like Protease + Polymerase +maybe Nitazoxanide will become available that MIGHT, JUST MIGHT give a decent percentage chance to clear despite the preexisting IFN resistance. These are one way roads, just like you cannot normally shake  interferon resistance, you cannot shake off specific antiviral resistance, once it is established, EVEN IF A SEQUENCE TEST WILL SHOW THAT YOU HAVE RETURNED TO WILD TYPE AND NO MORE MUTATIONS CAN BE  "FOUND".

So this is the first authoritative confirmation of what we suspected, ie. that  telaprevir could be a one-time shot because of being left with drug resistance.  Not only that, but any other drug with the same resistance profile is off the menu once specific antiviral resistance is established.  Might that mean any other ns3 PI?    

I was in a Prove2 no-riba arm, failed tx with a breakout and now have VX-resistant mutations.  I was just coming to terms with failing tx.  Now I've got to get my head round waiting for some other drug beyond VX that can kill those mutations.  When I did the trial I knew that the tx could fail but I didn't bargain on f***ing up my future chances of a cure for years to come because of it.  That was definitely not explained and if it had been I wouldn't have done it.  

Well, too late to whine about it now, but I am really pissed and I want to highlight for others entering a trial what the consequences might be.      

dointime                

[geterdone]

from your post… What I would like to know and if there is an answer, at what point dose the INF and Riba start doing more damage to our immune system than helping it fight the virus?

jasper

But in some cases it may possibly mean that the immune system itself has been changed or altered in a negative way by taking interferon and ribavirin, especially over a prolonged period of time and/or with multiple (failed) attempts. I recall once when HR stated that the immune system can be modeled and described using mathematical polynomials or differential equations, and within those diff eqs there are an array of constants or coefficients that define the characteristics of each person’s immune system (and these coefficients are unique to each person). If I recall what he said properly (please correct me if I’m wrong HR), these coefficients are permanently altered or changed when a person takes IFN and perhaps ribavirin too. If that’s true, then it would seem possible to me that the immune system *may* be altered in an undesirable way in some people when viewed within the context of (1) its ability to fight HCV alone, and (2) its ability to be as responsive to IFN and/or riba as it was during earlier course(s) of (failed) treatment.

[Whrose]

i do enjoy your posts!

one comment i have a problem with.

"I've often wondered if those treated unsuccessfully with SOC don't end up with SOC resistant viral strains but end up with SOC resistant immune system instead."

this is most interesting when considering the virus ability to modulate the host immune response on multiple pathways, however this alteration is not provoked by SOC but by the nature of viral evolution to survive and protect its genome.  maybe this is why with some individuals after repeated and or altered treatments may eventually have successful outcomes.  i also have hope that perhaps the development of meds that stimulate the Th1 immune response will be a useful adjunct to SOC for these people.

however exploring the drug resistant varients of treatment meds may be also a key reason (and one we may be able to prevent) for many of the response issues. would be nice to have improved diagnostics of this form of resistance and some stats on the numbers of this occuring.  this is where my interest becomes acute as drug resistance in any infection not only leads to evolution of superbugs but limits the effectiveness in what is already a limited arsenal of therapeutic alternatives with hcv or any pathogen.
i am thinking that viruses in particular over other micro organisms because of their replication and mutation rate will be a much more difficult organism to combat drug resistance issues. for sure we need more research in this area so as to provide the best and proper treamtnent regime and not create more difficult organisms.

thanks for always providing interesting insights.
Whrose

[gauf]

Mind if I quote you on that?

[Willy50]

: o      Now I'll never get my work done.  : )

Hey guys.....we're all on the same side; keep it light.

Mre.......your original quote, which HR quotes you and then I quoted HR using your quote to which you replied to me, quoting me quoting HR using your quote is not being used to put you on the spot.  : o

You made that quote some time ago but it is being used here today.  Our understanding of things may change and so it may not be fair to use that quote...... but on the other hand it will increase your google ranking.  : )

Thank you for the reply.  I take it as a kind response to my question.  I just stopped in for a work break and will digest this later...and try to answer it.  Some of it I have no answer for since we agree.

My main premise stands; what percentage will bcome null responders?  IF it is indeed a small number I think that our reaction to the viral resistance question may be over the top.  This is nothing new really is it?  I mean..... I've read the pharms say that it can't happen with interferon but I never quite understood/believed that virii couldn't mutate into more resistant versions.

I think the main thing that is unstated here is that we all want to know how it affects specific members.  We are talking about the principles generally but I think we all really want to know specifally in this thread for Dointime.  There are others here who have failed a Vertex trial and we all want to see them clear.  I still have hope that it can be done but perhaps I need to sit down and read the AASLD studies....which I haven't due to being out of town.

I'll be back later to respond but I still encourage people top remain positive.

thanks  and best,
Willy

[gauf]

No, I understand completely that it was "food for thought", and I know full well that the jury is out on the long term effects of these drugs. But like I said, what choice do we have? It is possible I may or may not develop some immune problems down the road, but all I can do now is try and get down that road!  I always appreciate your posts my friend.

[jmjm530]

You seem to take my statements as argumentative when I'm just expressing my overall take. I only put you in the "to" line because you brought the subject up, but my comments were to the group as well. And how I express my opinions to "Dointime" is "code" for nothing and frankly none of your business. Once again, your ad hominem response is not welcome, not that you seem to care.