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Interferon and Ribavirin: Mechanisms of Action, Resistance, and Why It Matters/
A new article on HCV - it is involved and you must register to view. It's free though and worth it if you want to learn about HCV treatment.
<A HREF="http://clinicaloptions.com/Hepatitis/Annual%20Updates/2006%20Annual%20Update/Modules/Chung/Pages/Page%201.aspx/">Interferon and Ribavirin: Mechanisms of Action, Resistance, and Why It Matters</A>
Mike
<A HREF="http://clinicaloptions.com/Hepatitis/Annual%20Updates/2006%20Annual%20Update/Modules/Chung/Pages/Page%201.aspx/">Interferon and Ribavirin: Mechanisms of Action, Resistance, and Why It Matters</A>
Mike
thanks - I tried to get into that article last night and couldn't -- had no problem with your link. downloaded was 51 pages so won't be reading it right now, but plan to soon.
kath
kath
great article, thanks mike.
I like the statement that hcv is a curable disease!
it does seem that IFN will need to remain in the picture, even with the new meds. but it could be adios, to riba.
I like the statement that hcv is a curable disease!
it does seem that IFN will need to remain in the picture, even with the new meds. but it could be adios, to riba.
Ah thank you Cuteus for the recap...I just don't have time to read 51 pages at work or I wont be working anymore ;)
I can't see IFN going anywhere for quite a while...until they come out with a completely new therapy it seems everything will revolve around it...and that they aren't really even focusing on trying to get rid of it really.
Which is too bad as it's much harder on the body I think than the Riba (although the riba gives us anemia for example it doesn't cause the autoimmune diseases that we are prone to and the serious health side effects).
Now that I'm down to only 800 mgs a day of Riba...I feel like I stopped taking it or something, it's cool. Just psychological but...as long as iit works LOL
I can't see IFN going anywhere for quite a while...until they come out with a completely new therapy it seems everything will revolve around it...and that they aren't really even focusing on trying to get rid of it really.
Which is too bad as it's much harder on the body I think than the Riba (although the riba gives us anemia for example it doesn't cause the autoimmune diseases that we are prone to and the serious health side effects).
Now that I'm down to only 800 mgs a day of Riba...I feel like I stopped taking it or something, it's cool. Just psychological but...as long as iit works LOL
I haven't studied the article as closely as I will but I don't see where you get the idea that Riba won't be needed.
From the article:
These data raise the possibility that RBV may not only be required in the liver but may also need systemic concentration for its effects. For instance, concentrations of RBV may be required for beneficial immunomodulatory effects or to reach extrahepatic reservoirs of HCV. Given the significant advance that RBV has represented in the management of chronic HCV infection, it is difficult to picture the use of antiviral therapy combinations without this agent (or its analogues) in the immediate future.
From the article:http://clinicaloptions.com/Hepatitis/Annual%20Updates/2006%20Annual%20Update/Modules/Chung/Pages/Page%206.aspx
Gotta cite the source. Mike
From the article:
These data raise the possibility that RBV may not only be required in the liver but may also need systemic concentration for its effects. For instance, concentrations of RBV may be required for beneficial immunomodulatory effects or to reach extrahepatic reservoirs of HCV. Given the significant advance that RBV has represented in the management of chronic HCV infection, it is difficult to picture the use of antiviral therapy combinations without this agent (or its analogues) in the immediate future.
From the article:http://clinicaloptions.com/Hepatitis/Annual%20Updates/2006%20Annual%20Update/Modules/Chung/Pages/Page%206.aspx
Gotta cite the source. Mike
I just wanted to let folks know that they can be updated on info such as this directly from clinical care options via email. I get it, you can get it too if interested. This article is very interesting, thanks for posting it.
http://clinicaloptions.com
http://clinicaloptions.com
The section on viral kinetics is interesting, and has been talked about by the drug cos. for their trials. For example, this modeling is (to the best of my knowledge) the one that VRTX used to determine 3 months could be the tx. duration.
There is something else in that, that is a point I made last year about Schering's PI. The 2 decline slopes are very important. Schering's problem, was, that there was a slight rebound in between phases. That told me that dosing might not be high enough. Now, they are exploring higher doses. If they had achieved higher concentrations in the liver, that wouldn't have happened, as it appears the drug was metabolized too quickly. Ritonavir boosting might help but I have read that it didn't help as much as one would have thought. Ritonavir boosting did have a significant effect on 950, which is why some speculate that further down the road, dosages might be able to be lowered.
The third slope is new to me.
There are those who feel riba might not be needed, that in effect, the new drugs would be in its place. Hopefully testing will show that to be the case. I have not read that far yet.
There is something else in that, that is a point I made last year about Schering's PI. The 2 decline slopes are very important. Schering's problem, was, that there was a slight rebound in between phases. That told me that dosing might not be high enough. Now, they are exploring higher doses. If they had achieved higher concentrations in the liver, that wouldn't have happened, as it appears the drug was metabolized too quickly. Ritonavir boosting might help but I have read that it didn't help as much as one would have thought. Ritonavir boosting did have a significant effect on 950, which is why some speculate that further down the road, dosages might be able to be lowered.
The third slope is new to me.
There are those who feel riba might not be needed, that in effect, the new drugs would be in its place. Hopefully testing will show that to be the case. I have not read that far yet.
"Other anti-HCV agents in development, such as HCV protease inhibitors, are expected to improve first-phase kinetics dramatically. If these agents are used in conjunction with PEG-IFN, might they obviate the need for RBV in the therapeutic armamentarium? If the effects of RBV are entirely antiviral, then this might be so and RBV use could be avoided. However, if RBV is acting independently as an immunomodulator, then it might not be easily substituted with other antiviral agents."
It seems they are asking a question, without an answer.
To the best of my knowledge, ribavirin is not an anti-viral. So, if it were an immunomodulator, then by their accounts it would still be needed.
However, one thing the article left out is that protease inhibitors are in effect, immunomodulators also if I read and remember the studies correctly. That is because of the studies that show that PI's restore the body's immune function by their action on deactivating the virus.
Not enough is understood about riba's role, but hopefully upcoming trials will show a lack of relapse without riba.
It seems they are asking a question, without an answer.
To the best of my knowledge, ribavirin is not an anti-viral. So, if it were an immunomodulator, then by their accounts it would still be needed.
However, one thing the article left out is that protease inhibitors are in effect, immunomodulators also if I read and remember the studies correctly. That is because of the studies that show that PI's restore the body's immune function by their action on deactivating the virus.
Not enough is understood about riba's role, but hopefully upcoming trials will show a lack of relapse without riba.
I skimmed a lot of the article quickly and extracted the main theme of each paragraph, also checked the summary which gave me the impression of phasing riba from new tx:
Application of mathematical models to viral kinetics may help elucidate the mechanisms of action of currently used antiviral therapy for HCV. Kinetic models of HCV indicate the presence of a rapid first-phase decline that lasts 24-48 hours and is IFN dose dependent, followed by a slower, second-phase decline. A late, third phase has been observed by some investigators.
IFN response is characterized by an early response followed by a more delayed adaptive (or cellular) response. During the early response, several signaling events ultimately lead to the activation of a very large number of IFN-stimulated genes. During the delayed response, the final clearance of virally infected cells and sustained virologic response can occur.
Investigational agents for the treatment of HCV are in various phases of development. The most promising class of compounds appears to be virus-specific protease inhibitors, which block the HCV NS3-4A serine protease enzymatic complex. Other agents in development include inhibitors of the HCV NS5B RNA
Application of mathematical models to viral kinetics may help elucidate the mechanisms of action of currently used antiviral therapy for HCV. Kinetic models of HCV indicate the presence of a rapid first-phase decline that lasts 24-48 hours and is IFN dose dependent, followed by a slower, second-phase decline. A late, third phase has been observed by some investigators.
IFN response is characterized by an early response followed by a more delayed adaptive (or cellular) response. During the early response, several signaling events ultimately lead to the activation of a very large number of IFN-stimulated genes. During the delayed response, the final clearance of virally infected cells and sustained virologic response can occur.
Investigational agents for the treatment of HCV are in various phases of development. The most promising class of compounds appears to be virus-specific protease inhibitors, which block the HCV NS3-4A serine protease enzymatic complex. Other agents in development include inhibitors of the HCV NS5B RNA
cuteus, I need more time too - I just received it today and skimmed through it. It does make for fascinating reading - well, sort of.
mrmeet, you're very welcome and it's nice to know that you're interested in the mechanics of this disease and its treatment.
Mike
mrmeet, you're very welcome and it's nice to know that you're interested in the mechanics of this disease and its treatment.
Mike
I do recall a study/article which postulated that 24 hour RNA was highly predictive of SVR but I cannot locate it right now. I'll look around and if I find it I'll post the site. Mike
Hi anybody and everybody.
Some time ago , I stumbled into an internet site that had information about the combo tx timeline. I't discussed what happened during the firt 12 hours of treatment , the next 24 , and so on and so on. I cant find it. Have any of you by any chance seen the data I'm talking about , and can you tell me where it is?
Thank you ahead of time...
Some time ago , I stumbled into an internet site that had information about the combo tx timeline. I't discussed what happened during the firt 12 hours of treatment , the next 24 , and so on and so on. I cant find it. Have any of you by any chance seen the data I'm talking about , and can you tell me where it is?
Thank you ahead of time...
Very interesting articles, the whole site is good, I figure if I spend 3 or 4 years there the I can go for my Doctorate...LOL
Have a great day!
Have a great day!
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