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
It's really good of you to spend the time drawing all this out for me. I'm keeping a copy just in case but hoping I don't need to go this route.
I decided to get myself out of the rut and got on a plane to Mexico. It's given me lots of new things to see and think about instead of sitting around nursing my post traumatic stress from the trial and 2 breakthroughs. I'm still keeping in touch with the forum but the change of climate is sure helping to get me out of the dumps, especially since I had to stay out of the sun all year because of the rash. I'd like to stay here for the winter, just chill, get a life, you know...
dointime
I decided to get myself out of the rut and got on a plane to Mexico. It's given me lots of new things to see and think about instead of sitting around nursing my post traumatic stress from the trial and 2 breakthroughs. I'm still keeping in touch with the forum but the change of climate is sure helping to get me out of the dumps, especially since I had to stay out of the sun all year because of the rash. I'd like to stay here for the winter, just chill, get a life, you know...
dointime
Thanks for the kind words, and I figured the docs you may have spoken with would provide vague non-commital answers or perhaps just shrug their shoulders. They're human beings too, and when confronted with treatment failures I think many of them take the evasive course to avoid unsettling conversations - for both their patients and themselves.
But with all of that said, you are not doomed to never be successfully treated again, far from it. And I do not necessarily think it will take years and years for you to access effective treatment that could very well give you your own SVR. It's very possible you could be cured using just SOC alone, especially with creative initial dosing and/or extented tx. Not a pleasant thought, I know, but again some of the hell that riba put you through may have been from the carryover effects of the telaprevir. A second round of SOC alone a year or so from now may turn out to be a lot more tolerable (skinwise) than you imagine it could be. No guarantees of course, but that is a possible outcome.
But outside of SOC, obviously there are already several fallow fields that very well may bear fruit for you in the near future too. Like alinia, obviously. Also boceprevir in a coupla years. And there may even be a shot at using telaprevir to help you too. Not all of your virus is telaprevir resistant, and the longer you stay off of treatment, the more telaprevir sensitivity will increase amongst the viral population. There will always be an archived tpvr resistant vestige remaining, but in my opinion that does not necessarily mean that telaprevir (or certainly another protease inhibitor) will not be able to be used to at least assist in some way during a creatively thought out treatment strategy.
I especially think it might be possible some of the newer dosing strategies that are being tested may turn out to be useful for some people (perhaps including yourself). For instance the way in which boceprevir has been dosed after 4 weeks of SOC in the SP trial. It's a matter of debate right now if this strategy is effective or not - but it might be effective in situations like yours. For instance, here's a hypothetical situation: lets say you decide to treat 2 years from now. By that time your virus should have mostly reverted to wild type, or types that are vulnerable to telaprevir (albeit the resistant vestige shall remain). And lets say you decide to predose with riba and perhaps procrit (depending on how anemic you were last time) for 3 weeks and then start out taking SOC+alinia for 4 weeks (perhaps doubledosing IFN for the first 2-4 weeks too). Assuming the predosed riba+SOC+alinia knocks out most of your virus within 4 weeks, and perhaps even to undetectability using a sensitive PCR (i.e. 10 IU/ml or better), it's likely that very little of the tpvr resistant virus will remain. It's even possible that virtually none of it will remain at that point. So perhaps adding telaprevir into the mix at that point could pay dividends and very quickly wipe out virtually all of the remaining virus. And even if there still is a tiny vestige of tpvr resistant bugs remaining, they'll still be vulnerable to the SOC and perhaps the alinia too. And by that time your immune system will have definitely been "turned on", and riba+IFN serum levels will have been fully saturated. So the usual "grace period" that the virus gets during the earliest phase of treatment with concurrent SOC+PI dosing will not be in the running. And I suspect it's that "monotherapish" grace period where the virus is mostly just confronted with the PI alone in the very beginning of concurrent PI+SOC tx (*especially* without riba!) that it gets just enough "liebensraum" to mutate up a resistance. But there won't be any liebensraum this time, the heat will be on and coming from all angles by the time the telaprevir is brought into the picture. Also, at that point the virus will have been swimming in ribavirin saturated blood for over a month. It is not completely understood how ribavirin works, but it is thought to cause the virus to mutate excessively and to cause unhealthy mutations in the virus. I can't know if the virus undergoing so many unhealthy mutations over the course of a month of strong antiviral therapy would be enough to mutate out any telaprevir resistance, but theoretically it seems plausible to me. Point being of course: combine the fact that VL is significanty cut down by week 4 (especially in regards to riba predosing), combined with the fact that SOC's referred immune responses are fully activated at 4 weeks (especially if IFN doubledosing occurs), combined with any role alinia may contribute (which I'm optimistic it will), combined with the mutative effects of riba perhaps diluting any remaining tpvr resistance, just *might* make the delayed introduction of telaprevir at that point a winning strategy. And in the unlikely event the telaprevir has minimal effect, I don't see any reason at all why it would disturb the effiicacy of the other drugs (i.e. you've got nothing to lose, side effects not withstanding).
Remember that you did respond to IFN in your previous treatment, and you also responded to ribavirin when it was latently introduced. You can respond again, with creative dosing and with the help of alinia and/or some new PI (perhaps even including telaprevir) you can get it done. And depending on how quickly you can squash your virus into UNDetectability, you might even be able to shorten your treatment to 24 weeks with reasonable safety (to help shorten the ordeal with the inevitable skin problems).
Hope you're feeling better soon and this isn't getting you too down. Hang in there, you'll make it out of this one way or another.
But with all of that said, you are not doomed to never be successfully treated again, far from it. And I do not necessarily think it will take years and years for you to access effective treatment that could very well give you your own SVR. It's very possible you could be cured using just SOC alone, especially with creative initial dosing and/or extented tx. Not a pleasant thought, I know, but again some of the hell that riba put you through may have been from the carryover effects of the telaprevir. A second round of SOC alone a year or so from now may turn out to be a lot more tolerable (skinwise) than you imagine it could be. No guarantees of course, but that is a possible outcome.
But outside of SOC, obviously there are already several fallow fields that very well may bear fruit for you in the near future too. Like alinia, obviously. Also boceprevir in a coupla years. And there may even be a shot at using telaprevir to help you too. Not all of your virus is telaprevir resistant, and the longer you stay off of treatment, the more telaprevir sensitivity will increase amongst the viral population. There will always be an archived tpvr resistant vestige remaining, but in my opinion that does not necessarily mean that telaprevir (or certainly another protease inhibitor) will not be able to be used to at least assist in some way during a creatively thought out treatment strategy.
I especially think it might be possible some of the newer dosing strategies that are being tested may turn out to be useful for some people (perhaps including yourself). For instance the way in which boceprevir has been dosed after 4 weeks of SOC in the SP trial. It's a matter of debate right now if this strategy is effective or not - but it might be effective in situations like yours. For instance, here's a hypothetical situation: lets say you decide to treat 2 years from now. By that time your virus should have mostly reverted to wild type, or types that are vulnerable to telaprevir (albeit the resistant vestige shall remain). And lets say you decide to predose with riba and perhaps procrit (depending on how anemic you were last time) for 3 weeks and then start out taking SOC+alinia for 4 weeks (perhaps doubledosing IFN for the first 2-4 weeks too). Assuming the predosed riba+SOC+alinia knocks out most of your virus within 4 weeks, and perhaps even to undetectability using a sensitive PCR (i.e. 10 IU/ml or better), it's likely that very little of the tpvr resistant virus will remain. It's even possible that virtually none of it will remain at that point. So perhaps adding telaprevir into the mix at that point could pay dividends and very quickly wipe out virtually all of the remaining virus. And even if there still is a tiny vestige of tpvr resistant bugs remaining, they'll still be vulnerable to the SOC and perhaps the alinia too. And by that time your immune system will have definitely been "turned on", and riba+IFN serum levels will have been fully saturated. So the usual "grace period" that the virus gets during the earliest phase of treatment with concurrent SOC+PI dosing will not be in the running. And I suspect it's that "monotherapish" grace period where the virus is mostly just confronted with the PI alone in the very beginning of concurrent PI+SOC tx (*especially* without riba!) that it gets just enough "liebensraum" to mutate up a resistance. But there won't be any liebensraum this time, the heat will be on and coming from all angles by the time the telaprevir is brought into the picture. Also, at that point the virus will have been swimming in ribavirin saturated blood for over a month. It is not completely understood how ribavirin works, but it is thought to cause the virus to mutate excessively and to cause unhealthy mutations in the virus. I can't know if the virus undergoing so many unhealthy mutations over the course of a month of strong antiviral therapy would be enough to mutate out any telaprevir resistance, but theoretically it seems plausible to me. Point being of course: combine the fact that VL is significanty cut down by week 4 (especially in regards to riba predosing), combined with the fact that SOC's referred immune responses are fully activated at 4 weeks (especially if IFN doubledosing occurs), combined with any role alinia may contribute (which I'm optimistic it will), combined with the mutative effects of riba perhaps diluting any remaining tpvr resistance, just *might* make the delayed introduction of telaprevir at that point a winning strategy. And in the unlikely event the telaprevir has minimal effect, I don't see any reason at all why it would disturb the effiicacy of the other drugs (i.e. you've got nothing to lose, side effects not withstanding).
Remember that you did respond to IFN in your previous treatment, and you also responded to ribavirin when it was latently introduced. You can respond again, with creative dosing and with the help of alinia and/or some new PI (perhaps even including telaprevir) you can get it done. And depending on how quickly you can squash your virus into UNDetectability, you might even be able to shorten your treatment to 24 weeks with reasonable safety (to help shorten the ordeal with the inevitable skin problems).
Hope you're feeling better soon and this isn't getting you too down. Hang in there, you'll make it out of this one way or another.
Hi mre - thank goodness you weighed in on this one. I knew I had something important to say but I just couldn't have mustered either the energy or the eloquence to say it like you have.
You said:
"But if you think that dointime is going to receive some kind of magical data from her doctor about the issue of telaprevir resistance as pertaining to ribaless treatment that will fly in the face of what we now know about it, think again"
You got that one right! I have asked about the problem of resistance and retreating several times to two doctors, both very experienced virologists, and all I have got is evasion. With HCV it is so easy to just trot out 'oh well, so little is understood ...it's too early to really say, .... blah blah'. Now I find out that the concept of the "archived antiviral resistance mutation" is well known among good hepatologists. Those snakes!
I just wouldn't like to see a whole new generation of multi-drug-resistant non-responders to be created in the next 10 years before a really effective drug combo comes along. This news has removed any doubt from my mind that I will wait for as long as my liver has got before doing another tx. HR's info has really made the difference.
Well, great to see you are still hanging out here even though you're SVR. How's the beer sampling going?
dointime
You said:
"But if you think that dointime is going to receive some kind of magical data from her doctor about the issue of telaprevir resistance as pertaining to ribaless treatment that will fly in the face of what we now know about it, think again"
You got that one right! I have asked about the problem of resistance and retreating several times to two doctors, both very experienced virologists, and all I have got is evasion. With HCV it is so easy to just trot out 'oh well, so little is understood ...it's too early to really say, .... blah blah'. Now I find out that the concept of the "archived antiviral resistance mutation" is well known among good hepatologists. Those snakes!
I just wouldn't like to see a whole new generation of multi-drug-resistant non-responders to be created in the next 10 years before a really effective drug combo comes along. This news has removed any doubt from my mind that I will wait for as long as my liver has got before doing another tx. HR's info has really made the difference.
Well, great to see you are still hanging out here even though you're SVR. How's the beer sampling going?
dointime
ROTFLMAO, good clip tho, sorry if I embarrassed you. It seems that the male ego will not allow the discussions of such topics as told by the death rate among men as a gender and why there are ten women for every man. The subject was brought up back then as now because it was directly related to the drugs being taken and what had rendered the problem incase some other unfortunate male may encounter the same problem while taking these meds in the course of treatment fore which it was brought up in the first place. Again, sorry for the embarrassment and the subject will never be broached here again. Lol!
jasper
Those were such kind and supportive words...thank you.
I definately believe, no matter the situation, it's always better
for everyone involved to not be negative...it only feeds on itself.
Thanks for the reminder.....this is why I keep coming back here,
for the advice...and the wonderful support.
It has been a great gift to me.
God Bless You
Love,
Yvonne
I definately believe, no matter the situation, it's always better
for everyone involved to not be negative...it only feeds on itself.
Thanks for the reminder.....this is why I keep coming back here,
for the advice...and the wonderful support.
It has been a great gift to me.
God Bless You
Love,
Yvonne
Oh yeah, I found a licensed specialist who can almost certainly "give you a hand."
http://youtube.com/watch?v=k61AN4fynDM
http://youtube.com/watch?v=3SCJLlSf21Y
http://youtube.com/watch?v=k61AN4fynDM
http://youtube.com/watch?v=3SCJLlSf21Y
What I'm trying to say is that this particluar subject just ain't my bag. Nuff said.
geterquote: " Mermeet, I had posted some time ago about small vain bleeds on the scrotum for which you had replied more or less little is known about it..."
Wha??? Dude, I never commented on your scrote veins. Mremeet don't do no scrote veins. Please, see a properly qualified and licensed scrotologist to address your concerns.
Wha??? Dude, I never commented on your scrote veins. Mremeet don't do no scrote veins. Please, see a properly qualified and licensed scrotologist to address your concerns.
Thanks! I guess the word damage was an extreme expression and that the word “alteration” would have been a better fit. Yes, our immune system is chemically altered by taking these meds for a prolong period of time and the possibility of lasting effects after stopping treatment all the sudden. This is where my focus is and I am starting to think what would be the best course of action to possibly head off what may or may not be a permanent autoimmune system problem or problems at the end of tx and how I am going to wean my self off these meds and hopefully allow my own immune system to start repairing any chemical alteration that may have been caused by the prolong use of the meds. I know this may be forward thinking and am sure others are just trying to get through the treatment as I was in the earlier stages of tx but with 12 weeks left I do not want to end tx cold as many before me had and end up with the possibility of any lasting effects of the meds. See my journal as to why I had focused in on the reply to you about immune system problems. Mermeet, I had posted some time ago about small vain bleeds on the scrotum for which you had replied more or less little is known about it, It has since stopped after reducing the riba from 1200 to 1000mg it took about three weeks to completely subside.
Thanks!
jasper
Thanks!
jasper
my heart of support to you now. i feel for your present challenge. you are in a tremendous fight right now and under the effects of these powerful meds. i wish there was an easy answer but unfortunately there isn't. the best we can do sometimes is not enough in our fight and the best our hep docs can do likewise sometimes is not enough.
but i will always hold out for hope rather than despair, positive attitude over giving up, knowledge over speculation, a doc who cares and fights the fight with me over the quack selling me false hope, and bravery over a cowards closet.
you are all of the best in our community and i am awed by your true grit. sleep well and happy dreams to you.
hugs.....Whrose
but i will always hold out for hope rather than despair, positive attitude over giving up, knowledge over speculation, a doc who cares and fights the fight with me over the quack selling me false hope, and bravery over a cowards closet.
you are all of the best in our community and i am awed by your true grit. sleep well and happy dreams to you.
hugs.....Whrose
i was reminded after consideration of mre's rant (affectionately said) regarding immune alteration from SOC of another interesting fact that liver disease from chronic hcv increases the risk for lymphoproliferative disease. hcv is not only hepatotrophic but also a lymphotrophic virus. although i remember the risk is low ~4-5% (correction requested), the point is that hcv may do more damage and immune sytem alteration in chronic time than SOC. i say this not to scare us but to cause us to consider that chronic infection may do more immune alteration than SOC presents which supports my theory. the incidence of cryoglobulinemia may also represent this link. our immune system may take a hit with this virus as our body mounts a viral defense. the added risk of stimulation of immunopatholgy with SOC or chronic infection represents valid concerns when we consider treatment risks vs chronic viral infection. the thoughts that hcv has the ability to replicate in certain immune cells is proven. i wonder that in time these sequalae of chronic infection will be better understood. in fact i look forward to this.
That was a help. Thanks so much for responding. I am going to have to sit down with dr. and not let his NP push me around anymore. I did mention Alinia...he said wait and see...
I have to be a better advocate for myself...
Good night and thanks again.
Yvonne
I have to be a better advocate for myself...
Good night and thanks again.
Yvonne
Sorry....I've been busy. I actually wrote out a long reply detailing point by point. I may PM it but the bottom line is that it just confuses things arguing about points likening or contrasting HCV and HIV. I also want to avoid strenuously arguing minutae especially since this is an area where the data is very sparse and theory, not fact and data rules. My heart is just not into arguing the points. I truely don't know the answers.
I care about how our relapsers are and I know you do too as well as HR and many others. I know we have to prepare ourelves for bad news. It will really smart IF it comes so close to the finish line.
I'd like to think I still presented my point, whether right or wrong. Current trials will answer our questions soon enough.
I'd still encourage people to stay optimistic. You can see strides being made every week on this board. Think what has been accomplished in just this last year. The years that come will be better still.
Be patient....we will all get there.
Best,
Willy
I care about how our relapsers are and I know you do too as well as HR and many others. I know we have to prepare ourelves for bad news. It will really smart IF it comes so close to the finish line.
I'd like to think I still presented my point, whether right or wrong. Current trials will answer our questions soon enough.
I'd still encourage people to stay optimistic. You can see strides being made every week on this board. Think what has been accomplished in just this last year. The years that come will be better still.
Be patient....we will all get there.
Best,
Willy
i will give my one cent to your question. other's more expereinced will certainly have more insight.
according to Dr Shiffman in his article at CCO a slow response is described as undetected viral load between wk 12 to wk 24. if you are detected at week34, by this definiton you would not be a slow responder. he also describes a partial responder as one who has a 2 log drop by week 12, but still positive at week 24. so by this definition it appears you would fall under the category of partial responder.
as HR pointed out there are shades of response that should be individually evaluated.
perhaps he will come on and give a better answer to your situation.
i also read a summary by Dr Hassanein at CCO that stated if one is detected at week 24 there is no possibilty of SVR on that same treatment and it should be modified with goal to get to undetected.
however it was not clear what changes would be the best in this situation.
your doc appears confident of your response by what you write. this has alot of weight. i am not sure what changes you have made to your tx but i do wish you the very best and will keep you in my prayers. stay positive.
btw. if it were me, i like the idea of adding alinia since you are still detected at week 34. for me it would make sense if you are in the fight to have all the tools available to do the job. did you ask your hep doc what he thought about it? what length of time are you planning at this point on present regime?
hugs
according to Dr Shiffman in his article at CCO a slow response is described as undetected viral load between wk 12 to wk 24. if you are detected at week34, by this definiton you would not be a slow responder. he also describes a partial responder as one who has a 2 log drop by week 12, but still positive at week 24. so by this definition it appears you would fall under the category of partial responder.
as HR pointed out there are shades of response that should be individually evaluated.
perhaps he will come on and give a better answer to your situation.
i also read a summary by Dr Hassanein at CCO that stated if one is detected at week 24 there is no possibilty of SVR on that same treatment and it should be modified with goal to get to undetected.
however it was not clear what changes would be the best in this situation.
your doc appears confident of your response by what you write. this has alot of weight. i am not sure what changes you have made to your tx but i do wish you the very best and will keep you in my prayers. stay positive.
btw. if it were me, i like the idea of adding alinia since you are still detected at week 34. for me it would make sense if you are in the fight to have all the tools available to do the job. did you ask your hep doc what he thought about it? what length of time are you planning at this point on present regime?
hugs
actually in another post HR complimented you on your perspective regarding resistance.
i do agree with you that this view is speculative. i enjoy it though.
to throw a wrench into SOC influenced immune changes,. i also entertained this. however in my personal experience. i developed auto immune arthropathy first sx before SOC.
i have speculated that chronic hcv had altered my immune sytem that allowed this situation to present. no doctor will deny or confirm though. so in my case the virus altered my immune system that left me predisposed to this. again this is my theory. but i would bet based on 3 generations of family medical hx with no auto immune arthropathy present that my immune system was altered from the virus. luckily for me, SOC was successful and my immune sytem was not resistant to the SOC.
as my rheumy patiently tells me. the immune sytem is complex and although we have made great strides there is so much we don't know yet.
you are one heck of a layman though, and have very good reasoning in the realm of speculation and rational deduction.
kudos
i do agree with you that this view is speculative. i enjoy it though.
to throw a wrench into SOC influenced immune changes,. i also entertained this. however in my personal experience. i developed auto immune arthropathy first sx before SOC.
i have speculated that chronic hcv had altered my immune sytem that allowed this situation to present. no doctor will deny or confirm though. so in my case the virus altered my immune system that left me predisposed to this. again this is my theory. but i would bet based on 3 generations of family medical hx with no auto immune arthropathy present that my immune system was altered from the virus. luckily for me, SOC was successful and my immune sytem was not resistant to the SOC.
as my rheumy patiently tells me. the immune sytem is complex and although we have made great strides there is so much we don't know yet.
you are one heck of a layman though, and have very good reasoning in the realm of speculation and rational deduction.
kudos
My brain is functioning on a very low level presently. I have reread this beaucoup times...yet frustratingly enough, I 'aint gettin' it. Could someone explain this 'as if' they were talking to a 5 y.o? From the little I have digested, it seems more than likely I fit the category of 'interferon resistant,' yet my tx dr. says, "No" I am a very sloooowww responder with a vl of 1350 at 34 (or so) wks...double dosing the last 10 (or so). Please help. I've been in bed for the past three days...and the bills jus' won't pay themselves....
I don't want to give up...especially if my Hep. Dr. is against me stopping.....
After reading up on Lonestar's journey through tx., I feel like I may have a chance with infergen...again, Doc nixed this idea too. I feel desperate enough to try to get this Alinia from Mexico...i'm at my wits end. I wonder if it would do any good at this stage of the war. It seems I would have little to worry about reg. toxicity...but what the heck do i know.......it's not cheap either...
I don't want to give up...especially if my Hep. Dr. is against me stopping.....
After reading up on Lonestar's journey through tx., I feel like I may have a chance with infergen...again, Doc nixed this idea too. I feel desperate enough to try to get this Alinia from Mexico...i'm at my wits end. I wonder if it would do any good at this stage of the war. It seems I would have little to worry about reg. toxicity...but what the heck do i know.......it's not cheap either...
Guys what I said was speculation, please don't take it too seriously or over simplify what I posed as a limited scope *possibility* as a proven or well supported fact (cuz it ain't!). And jasper you ask "at what point dose the INF and Riba start doing more damage to our immune system than helping it fight the virus? " Again I'm not suggesting it does "damage" to the immune system, what I'm suggesting is that it alters our immune system. It certainly alters it while we're on the drugs and it appears to alter it in a lasting way after we stop taking these drugs. For some people that long term (and perhaps permanent) alteration involves automimmune issues (sometimes serious), for others it may mean more colds and flu bugs, for others it may mean skin issues (psoriasis etc). And perhaps for others it may mean a decreased sensitivity to IFN in the event there are any future attempts at using it again - PERHAPS! (i.e. that possibility is certainly in no way a done deal) Please don't read too much into what is basically a speculative dining room table discussion amongst amateurs (aside from HR, obviously). And whrose thanks for the kind words, but when you say "i am just now really get the gist of what you and Hr meant by SOC resistance" please understand that I'm not speaking for HR when I postulated what I did above. I did reference what he said about the permanent alteration of our immune systems after taking IFN, but the rest of what I said he has not subscribed to nor agreed with (that I'm aware of). For all I know he thinks it's a buttload of tripe - so please don't be under the impression I'm speaking for him simply because this thread has a reference from him quoting me and then in one of my responses I quoted/referenced him. Sorry for any confusion, it was not intended.
oh dear. i am just now really get the gist of what you and Hr meant by SOC resistance.
i think i will take a while and digest this. it is surely a large plate of information to consider.
again thanks mre....
i think i will take a while and digest this. it is surely a large plate of information to consider.
again thanks mre....
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.
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.
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
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
: 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
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
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.
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.
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.
