Aa
Houston, this is 13...
I am beginning to think about my end of treatment plan and looking for thoughts on the subject. HR has discussed the tapering topic in the past.....
by HR
"It needs to be understood that when stopping IFN, a new form of antiviral defense against possible HCV remnants needs to take hold and establish itself - the adaptive Tcell response, that up to this point was greatly aided by the direct effect of IFN on the hepatocytes and the local intrahepatic immune cells. With this IFN aid gone all the burden is on the Tcell response, that will typically get stronger if more remnant viruses are seen ( if they can be seen now, because new epitopes are now present) - with incredible sensitivity, but it takes time to come to full swing and it can furthermore, at this very critical moment, be paralyzed by the prominent absence of innate signals needed to get adaptive Tcell responses going after IFN is abruptly missing from the equation. Here is one more specific EXAMPLE how the Tcell effect depends on the presence of some Interferon: The presentation of the viral epitopes is performed - as described in detail in an earlier post- by the cellular proteasome and the class I MHC molecules that bind the peptide and bring it to the surface for recognition by the "cognate" Tcell receptors of the "cognate" Tcell patrolling the liver."
He also recommended adding Lactoferrin at this time to help the immune system come "back online". Has anyone tried this? And any opinions on other immune enhancing supplements? Thanks.
---------------------------
"Houston, we need to go over those re-entry procedures so there are no foul ups, so here is what you are going to do, give us whatever you got so we can look em over. We are all a bit tired up here... and the earths getting awfully big in the window...."
"13... this is Houston, we are going to get those procedures to you just as soon as we possibly can. Ken Mattingly is in the simulator as we speak..."
"Roger that Houston... Kens working on it..."
by HR
"It needs to be understood that when stopping IFN, a new form of antiviral defense against possible HCV remnants needs to take hold and establish itself - the adaptive Tcell response, that up to this point was greatly aided by the direct effect of IFN on the hepatocytes and the local intrahepatic immune cells. With this IFN aid gone all the burden is on the Tcell response, that will typically get stronger if more remnant viruses are seen ( if they can be seen now, because new epitopes are now present) - with incredible sensitivity, but it takes time to come to full swing and it can furthermore, at this very critical moment, be paralyzed by the prominent absence of innate signals needed to get adaptive Tcell responses going after IFN is abruptly missing from the equation. Here is one more specific EXAMPLE how the Tcell effect depends on the presence of some Interferon: The presentation of the viral epitopes is performed - as described in detail in an earlier post- by the cellular proteasome and the class I MHC molecules that bind the peptide and bring it to the surface for recognition by the "cognate" Tcell receptors of the "cognate" Tcell patrolling the liver."
He also recommended adding Lactoferrin at this time to help the immune system come "back online". Has anyone tried this? And any opinions on other immune enhancing supplements? Thanks.
---------------------------
"Houston, we need to go over those re-entry procedures so there are no foul ups, so here is what you are going to do, give us whatever you got so we can look em over. We are all a bit tired up here... and the earths getting awfully big in the window...."
"13... this is Houston, we are going to get those procedures to you just as soon as we possibly can. Ken Mattingly is in the simulator as we speak..."
"Roger that Houston... Kens working on it..."
Bad Maths
After two weeks 1:32 of the drug etc
Should be 1:16th of the drug. then 1:64 after 3 weeks
CS
After two weeks 1:32 of the drug etc
Should be 1:16th of the drug. then 1:64 after 3 weeks
CS
"Jim - I think you're you're confusing half-life elimination with elimination."
Sorry Jim but aint they the same thing.
The elimination Half life of a drug is how long it takes to eliminate half the drug.
In pegasys’s case this is 80 hours on average so after one week you would have 1 quarter of the drug left in your system, if you were Mr/MS Average.
After two weeks 1:32 of the drug etc.
Aside from this being quite a deal quicker than the model HR suggests, It also depends on whether you are eliminating the drug faster or slower than the average.
So yes I can see how this natural taper can let some people down. It happens too fast.
You're comparing a 12-year old study that would be easy to implement (tapering) with a recent finding that would be very difficult to implement (if not impossible) in this country because HPLC testing for serum ribavirin is not available in clinical settings.
Not really. I was trying to show that an idea can be sound even if it hasn’t been thoroughly investigated. In any case If enough Drs wanted HPLC testing it would be available in the US or any other country for that matter.
1 or 2 studies that showed it improved response rates and it would be in use everywhere.
The study may even suggest that lower-doses of interferon should be investigated for months 6-12 instead of full-dose.
Have to agree with you there and makes you wonder why it hasn’t.
I know I would like to see the results of such a study
CS
Sorry Jim but aint they the same thing.
The elimination Half life of a drug is how long it takes to eliminate half the drug.
In pegasys’s case this is 80 hours on average so after one week you would have 1 quarter of the drug left in your system, if you were Mr/MS Average.
After two weeks 1:32 of the drug etc.
Aside from this being quite a deal quicker than the model HR suggests, It also depends on whether you are eliminating the drug faster or slower than the average.
So yes I can see how this natural taper can let some people down. It happens too fast.
You're comparing a 12-year old study that would be easy to implement (tapering) with a recent finding that would be very difficult to implement (if not impossible) in this country because HPLC testing for serum ribavirin is not available in clinical settings.
Not really. I was trying to show that an idea can be sound even if it hasn’t been thoroughly investigated. In any case If enough Drs wanted HPLC testing it would be available in the US or any other country for that matter.
1 or 2 studies that showed it improved response rates and it would be in use everywhere.
The study may even suggest that lower-doses of interferon should be investigated for months 6-12 instead of full-dose.
Have to agree with you there and makes you wonder why it hasn’t.
I know I would like to see the results of such a study
CS
Maybe this is for the same reason that he does not advocate dosing Riba according to serum concentration. Instead prefers dosing by weight still.
------------
You're comparing a 12-year old study that would be easy to implement (tapering) with a recent finding that would be very difficult to implement (if not impossible) in this country because HPLC testing for serum ribavirin is not available in clinical settings. Also, my guess is that Shiffman is quite flexible on riba dosing (other than weight) if he's in sync with some his collegues that I've consulted with. As to your half-life models, I'm no expert, but I think you're confusing half-life elimination with elimination. The taper, as Dr. Dieterich suggests seems to be built in and lasts to some degree or another for several weeks. My main point was that this is the critical period of taper per what I understood to be HR's thesis that there is an immune drop somewhere after the interferon is stopped. So, in effect, the natural taper covers this hypothetical period as I see it. That does not mean I'm not open to tapering as an add on, but I haven't yet seen a good case for it.
-- Jim
------------
You're comparing a 12-year old study that would be easy to implement (tapering) with a recent finding that would be very difficult to implement (if not impossible) in this country because HPLC testing for serum ribavirin is not available in clinical settings. Also, my guess is that Shiffman is quite flexible on riba dosing (other than weight) if he's in sync with some his collegues that I've consulted with. As to your half-life models, I'm no expert, but I think you're confusing half-life elimination with elimination. The taper, as Dr. Dieterich suggests seems to be built in and lasts to some degree or another for several weeks. My main point was that this is the critical period of taper per what I understood to be HR's thesis that there is an immune drop somewhere after the interferon is stopped. So, in effect, the natural taper covers this hypothetical period as I see it. That does not mean I'm not open to tapering as an add on, but I haven't yet seen a good case for it.
-- Jim
And who would I put my biggest believe in a doc who has been treating this HCV from the beggining or a researcher whos makes his living in coming up with wild theories,
and have no studys to back his theory with.
you a funny man
and have no studys to back his theory with.
you a funny man
Thanks for clearyfing, forgive me for jumping conclusions.
But you got to admitt when well-renowned doc as Schiffman who has been paricipating in a study 12 years ago ( the study was probaly performed 14 years ago) that seems to be very relevant for many whether to become SVR or not.
Still 12 years later doesn´t mention anything further about it, makes me wonder.
And who would I put my biggest believe in a doc who has been treating this HCV from the beggining or a researcher whos makes his living in coming up with wild theories,
and have no studys to back his theory with.
Dont forget Dr D who is also a well-renowned HCV treater and also have the same motivation as you and me to find the optimal cure being a relapser and all, don´t believe in it either.
Don´t get me wrong on this one, its guys that HR that makes the differens when their wild theories gets proven right, but until proven its still just a theory, and let me tell you we are many who got paranoid with the thought of an abrubt finish and even consider tapering down within the standard time ( although that is not the direct adwise from HR on the contrary maybe) specially if extending is not an option simply because our treating docs wont aprove to extending.
You will learn a lot in threads like this I think, so I wanna thank you jm and gauf for your solid interest in the subject, thats the forse thats helps me learn more and often if someone is posting something that event isn´t solid facts and totally correct from the beginning, thats what force your ( my ) brain to work a little more.
ca
PS Thx for the info on the differens between pegintron and pegasys could be an interesting question for someone whos on pegintron to ask Dr D.
But you got to admitt when well-renowned doc as Schiffman who has been paricipating in a study 12 years ago ( the study was probaly performed 14 years ago) that seems to be very relevant for many whether to become SVR or not.
Still 12 years later doesn´t mention anything further about it, makes me wonder.
And who would I put my biggest believe in a doc who has been treating this HCV from the beggining or a researcher whos makes his living in coming up with wild theories,
and have no studys to back his theory with.
Dont forget Dr D who is also a well-renowned HCV treater and also have the same motivation as you and me to find the optimal cure being a relapser and all, don´t believe in it either.
Don´t get me wrong on this one, its guys that HR that makes the differens when their wild theories gets proven right, but until proven its still just a theory, and let me tell you we are many who got paranoid with the thought of an abrubt finish and even consider tapering down within the standard time ( although that is not the direct adwise from HR on the contrary maybe) specially if extending is not an option simply because our treating docs wont aprove to extending.
You will learn a lot in threads like this I think, so I wanna thank you jm and gauf for your solid interest in the subject, thats the forse thats helps me learn more and often if someone is posting something that event isn´t solid facts and totally correct from the beginning, thats what force your ( my ) brain to work a little more.
ca
PS Thx for the info on the differens between pegintron and pegasys could be an interesting question for someone whos on pegintron to ask Dr D.
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