Aa
Digested the AASLD news, I am bummed too
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
"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
Dointime...
I don't wish to sound like a ninny -- for I am beyond lucky... But a trial is exactly that... A trial.
They do NOT know what is going to happen.
Anything - including death can happen at a trial.
I do not believe in trials for me.
I do not think I would be in the first groups of humans to test out a product --- I'm sorry. I just don't have that much faith in human science... YET...
There will be a time in the future - that humans will understand how we are exactly created - and what substances will do... They will understand the chemical components and they will be able to see more clearly what future results will be.
Until that day - however - trials are shots in the dark.
No one knows what will happen ---- for good or for bad... and how far in the future.
When you do a trial - you should know that.
You might cure --- you might die --- you might never be able to cure --- you might become INF resistant - you might cure half way then get another disease.... and so on ad infinitum.
I'm glad you are warning others - but you should not be so angry for yourself.
Keep your chin up --- and your hopes out...
There will someday be a cure.
Meki
I don't wish to sound like a ninny -- for I am beyond lucky... But a trial is exactly that... A trial.
They do NOT know what is going to happen.
Anything - including death can happen at a trial.
I do not believe in trials for me.
I do not think I would be in the first groups of humans to test out a product --- I'm sorry. I just don't have that much faith in human science... YET...
There will be a time in the future - that humans will understand how we are exactly created - and what substances will do... They will understand the chemical components and they will be able to see more clearly what future results will be.
Until that day - however - trials are shots in the dark.
No one knows what will happen ---- for good or for bad... and how far in the future.
When you do a trial - you should know that.
You might cure --- you might die --- you might never be able to cure --- you might become INF resistant - you might cure half way then get another disease.... and so on ad infinitum.
I'm glad you are warning others - but you should not be so angry for yourself.
Keep your chin up --- and your hopes out...
There will someday be a cure.
Meki
I was at Hep Dr. on Wed., I barely read about the conference before the appt. What I did ask was would I be considered interferon resistant?...He said NO...I am a slow responder. BTW, he was at AASLD. I don't know if he was playing golf, or downing shots at the bar..but. I am 35 weeks (or so) double dosing 2x a week...my last pcr showed a vl 1350...down from 45000 4 wks. b4. He gave the impression I should be happy....I asked about Alinia...he said maybe down the road..if necessary. So here i am double dosing...weight based should be taking 1000 mg. riba but an overdosing with 1400 mg.....and feelin' some rage today.
I feel like I'm between a rock and a hard place. I have just about had mor3e than I can take today...i can't seem to find a point for anything. Woe is me.
I feel like I'm between a rock and a hard place. I have just about had mor3e than I can take today...i can't seem to find a point for anything. Woe is me.
No disrespect to anyone, but I don't think things are necessarily as black and white as presented and the idea that you may have f*cked up future chances may not be correct. Please take your concerns to your doctor or another specialist and have them review your history against what is coming out of AASLD, including the resistance issue. I would think that if the repercussions of failed triple tx were that bad we'd be hearing more. At least don't give up hope without exploring things further.
-- Jim
-- Jim
Did you say you've been double dosing for 35 weeks and you still have viral load of 1350?
Have you gotten another opinion on your treatment? I forgot your stats, but I believe most stop at week 24 if still detectible unless you're treating only to improve liver condition as opposed to having reasonable odds of SVR. Also, never heard of anyone double dosing that long.
-- Jim
-- Jim
No...I started DD at 26 weeks..@ 10 -11 weeks upped riba from 1000 to 1400mg. I Have asked to stop tx....Hep Dr. (Director of Hep. Dept at a University Hosp) says...he cannot advise that at this time....
Trials are trials, yes, but the arms without ribavirin seemed to be a lost cause from start. I understand dointime's reaction. One would think it is not too much to ask to have the risk of resistance explained ahead of entering a trial.
Dr D told me that one of the PIs in trial, I think the one from BI, goes after a different sequence in the RNA and would be effective with people resistant to Telaprevir.
MEDICAL PROFESSIONAL
dointime:
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?
A poster at the AASLD investigated the question of Telaprevir/Boceprevir crossresistance by testing replicons wihich had the known Telaprevir mutations engineered into the replicons exposed to boceprevir. Boceprevir was still mainly effective against those. My realistic guess is that in clinical use one would see mild crossresistance, not precluding the use of Boceprevir in Telaprevir resistant patients, but somewhat reducing their SVR results. It might also strongly depend on which exact TPV mutation a patient has developed.
To Jim :
Things of course are not black and white, we are always dealing with sliding scales and varying percentages. To allow for a clear communication of a critical aspect, it is often necessary to communicate that main aspect without burying it inside numerous side issues and additional influencing variables.The preclusion of future effectiveness of combotherapies by "premature" use a solo antiviral that will later fail to provide its role in the otherwise useful combo is a delicate but important aspect that has, certainly in HIV and HBV antiviral therapy, dramatically reduced/permanently eliminated the chance of countless thousands to respond in a long term satisfactory supressive fashion to combos that are now on the table, with the realistic promise of lifelong viral supression and virtual elimination of disease sequelae. Thus treatment chances are to be carefully considered and your typical advice to approach a leading hepatologist that has a good knowledge base and intuitive capacity to juggle/consolidate the available options with a patients personal situation is certainly a wise one, unless you are an expert yourself. But don't have any illusions about the possibility of any individual to fully perceive and evaluate all the critical information that is presented at such a huge conference. Weeks, not days would be necessary to fully absorb all the truly important new aspects and smaller weigh-ins that are actually offered. Typically only the treatment aspects driven by larger pharmaceutical development can be paid attention to and these aspects are also the only ones for which there is enough money to persue the lasrge scale trials/proves that are typically required to cement at least a statistically sound result for any modality.
The industry sponsered "satellite meetings" are mostly the ones in which the practitioner receives his current education about progress and leading opinion by presentations/summaries from a handfull of hepatologists that certainly have their hands full in preparing for these extra meetings and dealing with elite patients that seek their advice. The disclosures that now are now mandatory before all presentations are also informative re driving forces behind the reshaping of strategic opinions.
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?
A poster at the AASLD investigated the question of Telaprevir/Boceprevir crossresistance by testing replicons wihich had the known Telaprevir mutations engineered into the replicons exposed to boceprevir. Boceprevir was still mainly effective against those. My realistic guess is that in clinical use one would see mild crossresistance, not precluding the use of Boceprevir in Telaprevir resistant patients, but somewhat reducing their SVR results. It might also strongly depend on which exact TPV mutation a patient has developed.
To Jim :
Things of course are not black and white, we are always dealing with sliding scales and varying percentages. To allow for a clear communication of a critical aspect, it is often necessary to communicate that main aspect without burying it inside numerous side issues and additional influencing variables.The preclusion of future effectiveness of combotherapies by "premature" use a solo antiviral that will later fail to provide its role in the otherwise useful combo is a delicate but important aspect that has, certainly in HIV and HBV antiviral therapy, dramatically reduced/permanently eliminated the chance of countless thousands to respond in a long term satisfactory supressive fashion to combos that are now on the table, with the realistic promise of lifelong viral supression and virtual elimination of disease sequelae. Thus treatment chances are to be carefully considered and your typical advice to approach a leading hepatologist that has a good knowledge base and intuitive capacity to juggle/consolidate the available options with a patients personal situation is certainly a wise one, unless you are an expert yourself. But don't have any illusions about the possibility of any individual to fully perceive and evaluate all the critical information that is presented at such a huge conference. Weeks, not days would be necessary to fully absorb all the truly important new aspects and smaller weigh-ins that are actually offered. Typically only the treatment aspects driven by larger pharmaceutical development can be paid attention to and these aspects are also the only ones for which there is enough money to persue the lasrge scale trials/proves that are typically required to cement at least a statistically sound result for any modality.
The industry sponsered "satellite meetings" are mostly the ones in which the practitioner receives his current education about progress and leading opinion by presentations/summaries from a handfull of hepatologists that certainly have their hands full in preparing for these extra meetings and dealing with elite patients that seek their advice. The disclosures that now are now mandatory before all presentations are also informative re driving forces behind the reshaping of strategic opinions.
Not having anything near your knowledge base, it's easier for me (and probably some others) to try and look at this in terms of clinical applications.
Given a hypothetical geno 1, stage 3, treatment naive, average pre-tx viral load, average bmi, etc, etc. This person has made a decision, based on a number of factors to treat now.
If they treat with Telaprevir triple, what we know seems to suggest around a 65% chance of SVR with 24 weeks interferon/riba exposure.
If they treat SOC, around 40-50% chance of SVR with 48 weeks interferon/riba exposure.
Which of these treatment courses would you recommend this hypothetical patient to do, assuming again that they have made the decision to treat now? The question I am asking you may be the choice faced by many when Telaprevir hits the market, which is projected in the near future.
-- JIm
Given a hypothetical geno 1, stage 3, treatment naive, average pre-tx viral load, average bmi, etc, etc. This person has made a decision, based on a number of factors to treat now.
If they treat with Telaprevir triple, what we know seems to suggest around a 65% chance of SVR with 24 weeks interferon/riba exposure.
If they treat SOC, around 40-50% chance of SVR with 48 weeks interferon/riba exposure.
Which of these treatment courses would you recommend this hypothetical patient to do, assuming again that they have made the decision to treat now? The question I am asking you may be the choice faced by many when Telaprevir hits the market, which is projected in the near future.
-- JIm
Same question for someone treatment experienced, who had a two-log drop by week 12 the first time, was UND by week 24 and then relapsed.
Same as above but without the two-log drop by week 12, although I think you already indicated they would not be a candidate for triple?
Lastly, I do understand that it takes time for things to filter out of AASLD, and do appreciate your 'heads ups' and analysis. But hopefully, this data will be assimilated into tx protocols/decisions by the better hepatologists and therefore my 'typical" recommendation. What other recommendation is there given the landscape? BTW I also recommended that this issue of viral resistance be brought to the hepatologist's attention as well as independently studied if the person is so motivated.
-- Jim
Same as above but without the two-log drop by week 12, although I think you already indicated they would not be a candidate for triple?
Lastly, I do understand that it takes time for things to filter out of AASLD, and do appreciate your 'heads ups' and analysis. But hopefully, this data will be assimilated into tx protocols/decisions by the better hepatologists and therefore my 'typical" recommendation. What other recommendation is there given the landscape? BTW I also recommended that this issue of viral resistance be brought to the hepatologist's attention as well as independently studied if the person is so motivated.
-- Jim
I suspect that we are just seeing the tip of the iceberg on the subject of drug resistance - a bit like the slowy unfolding subprime mortgages thing that's all over CNBC these days. It's bad news, one drip at a time with a real doozie now and then.
We're used to talking about retreating with SOC but the new drugs are going to be a whole different ball game. The failed tx'ers are going to end up with treatment logs full of lists of their particular resistant mutants, and there are going to have to be tests developed (already called for by another poster here) to find out all the resistances that are in the mix before treating somebody. I think there's a sea change happening here concerning retreatment that's got nothing to do with playing with the dosages or duration and all to do with finding favourable cross-resistance in the tx combo.
Jim, I think there's not much been heard about it so far because nobody yet is in a position to go for retreating with VX. I think there's going to be a few shocks if it really is not possible. I asked my study Prof. about my retreatment options and he said he thought I'd be better off next time with 2 active agents in the mix. HR's statement on resistance is the first decisive one I've seen anywhere.
Andiamo - thanks for the information, and it's especially good to know that at least somebody is actively thinking about what to do about the potential hordes of people that will be made resistant to the new drugs, in addition to the hordes of people who already are resistant to SOC.
We're used to talking about retreating with SOC but the new drugs are going to be a whole different ball game. The failed tx'ers are going to end up with treatment logs full of lists of their particular resistant mutants, and there are going to have to be tests developed (already called for by another poster here) to find out all the resistances that are in the mix before treating somebody. I think there's a sea change happening here concerning retreatment that's got nothing to do with playing with the dosages or duration and all to do with finding favourable cross-resistance in the tx combo.
Jim, I think there's not much been heard about it so far because nobody yet is in a position to go for retreating with VX. I think there's going to be a few shocks if it really is not possible. I asked my study Prof. about my retreatment options and he said he thought I'd be better off next time with 2 active agents in the mix. HR's statement on resistance is the first decisive one I've seen anywhere.
Andiamo - thanks for the information, and it's especially good to know that at least somebody is actively thinking about what to do about the potential hordes of people that will be made resistant to the new drugs, in addition to the hordes of people who already are resistant to SOC.
Of course you understand that I was using the word "better" globally and not in comparison with yourself. Just wanted to clarify as communication has a tendency to go awry on the internet :)
Ladywhy,
I can't believe you're at 14oo riba and twice weekly peg at week 35 and still not UND.
Seems like something's amiss here.
And it's no WONDER you're having a rough time. I'm amazed you still have the strength to type let alone string together a couple of coherent sentences. I'm gonna email you something that happened to me today which might, at least, make you laugh at just how far riba rage can go.
Dointime,
Again, I'm so sorry for your predicament.
To all,
Just a hypothetical question/observation;
I have had multiple allergies for decades which ended in infections, sinus surgeries, etc., but no Dr. gave me much relief until 10 or 15 years into the process when i was lucky enough to find an allergist who THOROUGHLY tested me multiple times and then put me on a completely indiviualized series of injections. He's now the head of the State Board of Allergies and Immunology.
I'm wondering if, as has been mentioned on Forum and in a number of recent hep-c studies, future treatment might be headed to a much more individually tailoroed approach.
Thoughts?
wyntre
I can't believe you're at 14oo riba and twice weekly peg at week 35 and still not UND.
Seems like something's amiss here.
And it's no WONDER you're having a rough time. I'm amazed you still have the strength to type let alone string together a couple of coherent sentences. I'm gonna email you something that happened to me today which might, at least, make you laugh at just how far riba rage can go.
Dointime,
Again, I'm so sorry for your predicament.
To all,
Just a hypothetical question/observation;
I have had multiple allergies for decades which ended in infections, sinus surgeries, etc., but no Dr. gave me much relief until 10 or 15 years into the process when i was lucky enough to find an allergist who THOROUGHLY tested me multiple times and then put me on a completely indiviualized series of injections. He's now the head of the State Board of Allergies and Immunology.
I'm wondering if, as has been mentioned on Forum and in a number of recent hep-c studies, future treatment might be headed to a much more individually tailoroed approach.
Thoughts?
wyntre
"you cannot shake off specific antiviral resistance, once it is established,"
HR - Just to say thank you for this very important information which I have not been able to obtain anywhere else. I do wonder why not, considering it is such an essential consideration for anyone planning to treat with the direct antivirals.
HR - Just to say thank you for this very important information which I have not been able to obtain anywhere else. I do wonder why not, considering it is such an essential consideration for anyone planning to treat with the direct antivirals.
Just my 2 cents and believe me, it isn't worth any more than that. LOL! I agree with Jim that it isn't all black and white as he and HR have pointed out. Some of us don't know if we are null or partial responders.
HR, thanks for explaining how AASLD happens. Another thing to point out is that there are multiple sessions going on at one time so you really have to pick and choose. We were lucky enough to attend a satellite symposium which allowed us to get the resistance info from some pros who I have already mentioned. We also attended a Meet the Professor luncheon and got 1 hour of Drs. Zezeum and Sulkowski. There were 50 attendees, not very many when there are, I believe, over 4000 people at the conference. There were at least 3 other luncheons that we believe we would have benefited from going to. So just from the way the conference is set up, practitioners cannot get to hear everyone.
NIH Claims that there were 11,300 gastrodocs in the USA in 2003. Tht doesn't count the other docs who take care of hep patients such as infectious disease doctors and a few other specialties. So while 4000 at the conference seems a pretty helfty number, it also includes anyone who is involved in working with hep C patients. I don't know how long it takes all this news to become common knowledge for the hometown doctor.
HR, thanks for explaining how AASLD happens. Another thing to point out is that there are multiple sessions going on at one time so you really have to pick and choose. We were lucky enough to attend a satellite symposium which allowed us to get the resistance info from some pros who I have already mentioned. We also attended a Meet the Professor luncheon and got 1 hour of Drs. Zezeum and Sulkowski. There were 50 attendees, not very many when there are, I believe, over 4000 people at the conference. There were at least 3 other luncheons that we believe we would have benefited from going to. So just from the way the conference is set up, practitioners cannot get to hear everyone.
NIH Claims that there were 11,300 gastrodocs in the USA in 2003. Tht doesn't count the other docs who take care of hep patients such as infectious disease doctors and a few other specialties. So while 4000 at the conference seems a pretty helfty number, it also includes anyone who is involved in working with hep C patients. I don't know how long it takes all this news to become common knowledge for the hometown doctor.
I'm sorry you're feeling so bummed out about what happened, I don't blame you. But really, I think you have good reason to be hopeful, especially considering you do have minimal fibrosis. Telaprevir sure ain't the only game in town, there's new stuff popping up all the time. It really seems like we're entering a golden era of HCV antiviral research and development, every year seems to bring more news and more hope. I think HCV will go the way of polio within ten years, there just seems to be a frenzy of development now that the drug co's really see the possibilities, both pharmacological and in the enormous potential for profit.
Anyway, as far as your particular situation is concerned, take a look at alinia. Sure, we don't really know it'll work effectively for geno 1's, but it probably will offer at least a reasonable amount of performance. And it might simply kick a$$, don't write it off or assume it's a dud just because the data hasn't been produced for geno 1's yet. Plus it has absolutely nothing to do with any protease inhibitors (including telaprevir), so you certainly don't have any alinia resistant strains. And look how alinia just seemed to pop out of nowhere (at least for me it did). I always hear about all these vague references about "promising" prelim anti-HCV test results for certain unfamiliar drugs, and then I forget about them because no one is talking about them anymore. Either they prove disappointing later or they're discovered to have toxicities etc and then they fall off the map. But once in a while one of those quasi-obscure drugs you heard about once or twice in the background noise unexpectedly steps forward and says "HELLO". Right now alinia seems to fit that bill and to a lesser extent SCH503034 (boceprevir). And it's just a matter of time before a polymerase inhibitor makes it's way to the front of the line too. Sooner or later they'll be able to kludge together some kind of combination of drugs that will kick your virus' a$$, and kick it for GOOD this time. You just wait and see. And yes I know that you had a real tough time with the riba, I did too. And yes it looks like riba is going to be with us for some time now. But I also think at least some of what you went through riba-wise was as a consequence of the after-effects of your time on telaprevir too (I know the telaprevir skin effects lasted throughout my treatment, long after I stopped taking it). And some people have a very dermatolgically troublesome initial tx, but their subsequent tx(s) are not as bad. That's a possible scenario for you too, just because you got hammered the first time around that does not mean by definition that the exact same thing will happen again. Also, getting back to telaprevir for a moment, even if you do retain a certain percentage of the telaprevir resistant virus, the longer you stay off any tx drugs, the more your viral population will return to wild type. Yes there will probably always be a vestige of the telaprevir resistant virus within you, but its exclusive numbers will probably fade very significantly over time. Eventually the ratio between telaprevir resistant types and wild types (that are telaprevir sensitive) will shift so that the resistant types will be in a small minority (and as far as I know a very small minority if you've been off treatment for a long time). Telaprevir might still be used (along with other drugs) to help wipe out the non-resistant strains, serving to get your VL down sooner rather than later. It may not have the same coup de grace quality it would have in a naive patient, but it may turn out to still serve a useful, (albeit muted), purpose (assuming the other drugs are effective in the absence of telaprevir as well).
Lastly, I agree with you about what you said about the informed consent issues. We all should have been informed of the possibility of being stuck with a resistant strain, especially depending on what group we were put into (i.e. the 12 weeks with and especially without riba). I mean, I know in the beginning no one knew if VX would work without the riba, and it was not known just how long it would take to work its magic. But still I think enough was known by the time prove 1 and certainly prove 2 commenced that we should have been warned about that possibility. I've never seen the consent form for the earlier phase 1 monotherapy trials, but I would suspect they say nothing about anti-virologically "shooting your wad" by enrolling in those trials either. And even if it were spelled out in doctoresque techno-speak, how many ordinary people would really get it anyway? I sometimes think of those people who stepped up for the early monotherapy trials, and I'm sure many continue to do so for the newer drugs in development. Their doctors probably tell them something like "Oh this is an exciting new drug, very promising possibility of a new cure". Probably parsing their words carefully so that technically they're not saying anything untrue, but effectively leading an immunological lamb to the slaughter (especially in the case of those with advanced fibrosis). On the other hand, where would any of us be if someone didn't either knowingly or unknowingly be the first over the trenches? I'd be lying if I said I didn't deliberately wait until I thought my own chances were "sporting" before signing up for prove 1. I take cold comfort in the knowledge that someone did take those earliest steps, not just for myself but for all of us. To a lesser extent both you and me carried the flag a bit further at our own risk and personal sacrifice, but at what price? I'm just sorry things worked out the way they did for people like you and nick and travelmom and amanda - SUCKS.
Anyway, as far as your particular situation is concerned, take a look at alinia. Sure, we don't really know it'll work effectively for geno 1's, but it probably will offer at least a reasonable amount of performance. And it might simply kick a$$, don't write it off or assume it's a dud just because the data hasn't been produced for geno 1's yet. Plus it has absolutely nothing to do with any protease inhibitors (including telaprevir), so you certainly don't have any alinia resistant strains. And look how alinia just seemed to pop out of nowhere (at least for me it did). I always hear about all these vague references about "promising" prelim anti-HCV test results for certain unfamiliar drugs, and then I forget about them because no one is talking about them anymore. Either they prove disappointing later or they're discovered to have toxicities etc and then they fall off the map. But once in a while one of those quasi-obscure drugs you heard about once or twice in the background noise unexpectedly steps forward and says "HELLO". Right now alinia seems to fit that bill and to a lesser extent SCH503034 (boceprevir). And it's just a matter of time before a polymerase inhibitor makes it's way to the front of the line too. Sooner or later they'll be able to kludge together some kind of combination of drugs that will kick your virus' a$$, and kick it for GOOD this time. You just wait and see. And yes I know that you had a real tough time with the riba, I did too. And yes it looks like riba is going to be with us for some time now. But I also think at least some of what you went through riba-wise was as a consequence of the after-effects of your time on telaprevir too (I know the telaprevir skin effects lasted throughout my treatment, long after I stopped taking it). And some people have a very dermatolgically troublesome initial tx, but their subsequent tx(s) are not as bad. That's a possible scenario for you too, just because you got hammered the first time around that does not mean by definition that the exact same thing will happen again. Also, getting back to telaprevir for a moment, even if you do retain a certain percentage of the telaprevir resistant virus, the longer you stay off any tx drugs, the more your viral population will return to wild type. Yes there will probably always be a vestige of the telaprevir resistant virus within you, but its exclusive numbers will probably fade very significantly over time. Eventually the ratio between telaprevir resistant types and wild types (that are telaprevir sensitive) will shift so that the resistant types will be in a small minority (and as far as I know a very small minority if you've been off treatment for a long time). Telaprevir might still be used (along with other drugs) to help wipe out the non-resistant strains, serving to get your VL down sooner rather than later. It may not have the same coup de grace quality it would have in a naive patient, but it may turn out to still serve a useful, (albeit muted), purpose (assuming the other drugs are effective in the absence of telaprevir as well).
Lastly, I agree with you about what you said about the informed consent issues. We all should have been informed of the possibility of being stuck with a resistant strain, especially depending on what group we were put into (i.e. the 12 weeks with and especially without riba). I mean, I know in the beginning no one knew if VX would work without the riba, and it was not known just how long it would take to work its magic. But still I think enough was known by the time prove 1 and certainly prove 2 commenced that we should have been warned about that possibility. I've never seen the consent form for the earlier phase 1 monotherapy trials, but I would suspect they say nothing about anti-virologically "shooting your wad" by enrolling in those trials either. And even if it were spelled out in doctoresque techno-speak, how many ordinary people would really get it anyway? I sometimes think of those people who stepped up for the early monotherapy trials, and I'm sure many continue to do so for the newer drugs in development. Their doctors probably tell them something like "Oh this is an exciting new drug, very promising possibility of a new cure". Probably parsing their words carefully so that technically they're not saying anything untrue, but effectively leading an immunological lamb to the slaughter (especially in the case of those with advanced fibrosis). On the other hand, where would any of us be if someone didn't either knowingly or unknowingly be the first over the trenches? I'd be lying if I said I didn't deliberately wait until I thought my own chances were "sporting" before signing up for prove 1. I take cold comfort in the knowledge that someone did take those earliest steps, not just for myself but for all of us. To a lesser extent both you and me carried the flag a bit further at our own risk and personal sacrifice, but at what price? I'm just sorry things worked out the way they did for people like you and nick and travelmom and amanda - SUCKS.
Jim pinpointed some very interesting issues above with his questions about treating with or without telepravir in the future.
MEDICAL PROFESSIONAL
The concept of the "archived antiviral resistance mutation" was introduced by Doug Richman, a researcher/doctor whot was in charge of several HIV combo trials. It is well known among good hepatologists, but not a pleasant topic to bring up with a patient on a limited time frame.That the price for using a current chance is to possibly foul up great future chances is not something a practitioner will wish to discuss with a patient - and many are actually not really aware of this.
The true issue is furthermore complicated by the fact that resistance mutations are in themselves of variable consequence to the immediate viral fitness and to the crossresistance effects on similar yet somewhat different drugs.
But as a general rule there is a development of ever increasing "multidrug resistance " when monotherapies are added sequentially with an eventual burnout of options and a monster of a virus that resists everything, which is an outcome that the rules of evolution unfortunately clearly predict, if you do not block that evolution at an early point in that particular swarm of virus in patient X by rapidly reducing replication/genomic power using second and even third antivirals to stop the proliferation/de novo development of that very small original popluation that carries that critical resistance mutation/s.
So it is well established wisdom in therapeutic virology that a potent combo should be used first line that crossprotects each of its members from resistance developments and not to play around with sequential monotherapies. The fact that drugs are developed according to their pipeline and come out one at a time , while necessitated by the prudent precautions in drug development, fosters sequential monotherapy/pseudomonotherapy for the unfortunate that are in need for therapy at such historical times before the full cocktails are in place.
The true issue is furthermore complicated by the fact that resistance mutations are in themselves of variable consequence to the immediate viral fitness and to the crossresistance effects on similar yet somewhat different drugs.
But as a general rule there is a development of ever increasing "multidrug resistance " when monotherapies are added sequentially with an eventual burnout of options and a monster of a virus that resists everything, which is an outcome that the rules of evolution unfortunately clearly predict, if you do not block that evolution at an early point in that particular swarm of virus in patient X by rapidly reducing replication/genomic power using second and even third antivirals to stop the proliferation/de novo development of that very small original popluation that carries that critical resistance mutation/s.
So it is well established wisdom in therapeutic virology that a potent combo should be used first line that crossprotects each of its members from resistance developments and not to play around with sequential monotherapies. The fact that drugs are developed according to their pipeline and come out one at a time , while necessitated by the prudent precautions in drug development, fosters sequential monotherapy/pseudomonotherapy for the unfortunate that are in need for therapy at such historical times before the full cocktails are in place.
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
