I never have believed in the theory that with treatment the virus becomes resistant. I know that it seems counterintuitive but I treated for over two years and when I treated the third time with optimal doses I responded probably just as if I were treatment naive. I know many people talk about the virus acquiring resistance but I don't buy it. I really cannot advise you with any degree of confidence because I don't know much, if anything, about the viral kinetics of the Vertex PI. I do wish you and Amanda the very best and I am believing that the best is coming and that your news will be good. Mike.
Can't remember the details due to brain fog, but I did read a paper that said the virus does develop resistance, but reverts to the wild state very quickly when treatment stops.
There was an implication that if someone re-treated after 6 months or so, they would be starting fresh. I hope Jim or someone whose brain still works remembers the paper and the link to it.
This is a good question for a liver specialist, although wouldn't be surprised if you get conflicting answers.
Most seem to favor a "wait" period between treatments, from 6-12 months. Not sure if the reason has anything to do with "resistance" or they just want to give the body, mind and soul a chance to heal before abusing it again. We did have a few members, however, who treated almost immediately after relapse, but not sure how they ended up. Kalio1 comes to mind, and my best recollection is that she's still on treatment, or at least tapering off. Not 100% sure on that, although you could probably post to someone who is in touch with her, such as NYGirl.
I do agree with Mike, that there apears to be no resistance -- at least with SOC -- at least with the waiting period most people seem to take between treatments. We just have too many folks who re-treated successfully here. Is there any resistance if you re-treat right away, or with Teleprevir? That I really wouldn't want to venture a guess.
And as to your question about adding ribavirin at this point. Again, I don't think anyone has the answer to that, but my unprofessional guess -- and it's only that -- is that she should take a rest period of around a year and then start again with triple. Of course, she should discuss these options with a liver specialist.
First in the decision tree should be if Amanda's current status (i.e. - liver histology) calls for something more immediate (i.e. - re-tx'ing) - or the possibility of waiting. Given that she's a cirrhotic, my guess would be a lean towards the former. That being said, if you were to wait for triple-therapy, I would imagine that your wait would me a matter of years - not months - given that FDA approval for Vertex is not anywhere that close (nor a given, for that matter). Unless, perhaps, as a previous trial participant she would have some sort of 'compassionate-care' exemption that would allow her access down-the-road before any approval?
What you also want to talk about and consider with her docs/specialists is the possibility of some kind of maintenance - low-dose interferon, alinia, statins - or a combination of them (all depending on how 'radical' your docs may be, given that only the interferon is currently approved for Hep C). If you are going to wait - or have to wait - you sure would want to try and do whatever is possible to slow/halt progression.
As far as adding the riba to the mix at this stage of the game, I'm assuming her body has already been exposed to it in previous tx's (and at SOC levels). If that's the case, any 'resistance' would already have occurred during those past tx's. So, if her docs are willing to go from double therapy to triple at this point in time, her labs would most likely tell the story of any 'riba-resistance' in a relatively short period of time.
May God's blessings and mercy be upon you, Amanda and her caregivers.
have a look at a post about alinia from yesterday by ala girl....can you weigh in?
Travelmom - I don't know the answer to your question but below are some thoughts which I think are relevant and might help you decide. It may depend on your daughter's VL results. I mean, if her VL was just skimming UND like yours did then adding riba might put the final nail in the coffin for the virus. But if the breakout is a large number and holding steady (as mine was) then maybe it's not as favourable. But will you be able to get all the VL results or will you just be told if there has been a breakout?
Anyway, viral resistance to VX certainly has occured if there has been breakthrough. After VX dose termination a proportion of the viral breeding stock reverts back to wild-type within 7 months. It is not yet known whether the hangover from the resistance would be a problem next time around when treating with the triple therapy but it can't be ruled out. My opinion is that there will still be a small pool of VX resistant virus left and we don't know whether hitting it hard with the triple therapy next time around will wipe it out. Personally I'm not counting on it.
Next, as long as the VX is present it still has the function of preventing the resistant virus reverting back to wild-type. So if the ribavirin were to be introduced at this time, there would be one less place for the virus to run to get round the riba+inf combo. I believe I'd have had a better chance if I had continued on the triple therapy rather than plain SOC but would it have got me to SVR - I don't know. In my case I had a 2nd breakthrough on SOC and I now know I should have high-dosed the riba (god help me for the rash). In your daughter's case I don't know how her body deals with riba. On her previous tx what was the reason for failure, relapse, breakthrough, slow/non responder?
Lastly I'd like to add something which mremeet wrote back in May but unfortunately I can't find the link so I'm going to paste the quote here and hopefully he won't mind.
May 2007, mremeet wrote :-
The only caveat I might add in favor of continuing with telaprevir+SOC, would be for the following reason: ribavirin is thought to cause the virus to become genetically unstable. It is thought to cause the virus to mutate more often and in a more dramatic and uncontrolled manner when compared to its normal unhindered mutation rate. Mutations normally are what make the virus so hardy and adaptable to various natural and drug induced antiviral insults against it. Considering the virus' collossal population size (i.e. breeding stock) and rapid reproductive rate, mutations normally work in its benefit - to a point that is. If you can push the virus into mutating at a much more aggressive pace and with more significant types of mutations, then you can effectively cause it to mutate itself out of existence. The ribavirin may cause it to become "unfit" over time, causing huge numbers of the virus to have serious "birth defects" which can either hinder its ability to reproduce or stop it altogether. And those virus remaining that can reproduce will pass on their damaged RNA sequence to their offspring, thereby saddling them with the same defects the parent possessed. The cycle will continue to repeat over and over again while in the mutating presence of ribavirin and antiviral action of IFN, eventually resulting in eradication.
But under the circumstances described above, since the mutation rate has been increased, its possible a pre-existing VX resistant dominant population could be mutated out of its resistance. The traits of VX resistance would no longer selectively survive if the mutation rate was increased to the point where those traits simply could not be preserved nor retained from generation to generation anymore. And if that were to happen, the telaprevir could once again play a significant antiviral role, changing the stage so that there are now three effective antiviral actions at work simultaneously. Of course all of this is premised on the likely (and yet unproven) theory that ribavirin actually works in the manner speculated.