Aa
hepatitisresearcher
Your opinion please? Lets say a patient went thru treatment (1b) pegasys/copegus 180/1200 for 48 weeks, starting VL was 10 mil, middle aged male, slight liver damage, still detectable at 600 week 12, clear week 16 (less than 50), relapsed, waited 3 months and started treatment over, VL 500,000, double dose pegasys 4 weeks, 1400 copegus, no VL detected at week 4 using heptimax, did shot every five days from week 4 thru week 12, did 1600 copegus for month and half, waited full seven days at week 12 and got negative heptimax, doing 180/1200 rest of treatment, ast/alt normal at week 12, does this person have the same chance with RVR statistics (as high as 85% SVR) with 48 weeks, or are those RVR statistics only good for someone who does treatment the first time using the SOC? I hope you can understand what I’m asking here?
yes - good point - in fact given the high rate of polymorphism in the genome distribution of a typical infection it may well be the case that nearly all viable genomes already exist. Thus time may not be as relevant a factor as simply the size of the survivor population and the extent of its handicaps (the "one legged, two-fingered, tongueless" Will Smiths of viral Manhattan). From AASLD abstract LB8 on TVR mutations :
"In the TVR groups, viral breakthroughs were associated with the selection of known TVR-resistant variants. The breakthrough rate in the TVR/P group was higher than in the TVR/P/R groups, suggesting that suboptimal inhibition of viral replication provides a greater probability for selection of TVR-resistant variants. Some subjects with viral breakthrough on TVR had a subsequent decline in HCV RNA during treatment with P/R, indicating that emergence of TVR-resistance does not preclude response to P/R."
"In the TVR groups, viral breakthroughs were associated with the selection of known TVR-resistant variants. The breakthrough rate in the TVR/P group was higher than in the TVR/P/R groups, suggesting that suboptimal inhibition of viral replication provides a greater probability for selection of TVR-resistant variants. Some subjects with viral breakthrough on TVR had a subsequent decline in HCV RNA during treatment with P/R, indicating that emergence of TVR-resistance does not preclude response to P/R."
willingquote: "If you could knock off enough of the total virus quickly enough there might be so few survirors left they might not be able to find the necessary escape mutation in time. For vx this doesn't seem to be the case, within a few weeks the survirors have found the way out..."
Not to nitpick, but the virus does not necessarily have to come up with a telaprevir resistant strain "on the fly" in order to survive after the anti-viral onslaught initiates in all patients. Many patients were tested for PI/telaprevir resistant virus prior to being given telaprevir (and other PI's), and in a fair number of them either a partially or wholly resistant virus was found to already be in existence (albeit in very small numbers). So the mechanism for survival in the face of a PI attack wouldn't necessarily always be a purely adaptive one borne of a ferocious rate of mutative iterations and managing to come up with that "one in a trillion" just in the nick of time during the onslaught. It could simply be a case of the non-resistant variants being wiped out, and the very few pre-existing resistant types simply moving in and taking over (especially in the case of PI monotherapy). That is unless there are mutliple anti-viral modes of efficacy in play to keep this from happening, as in VX+SOC.
Not to nitpick, but the virus does not necessarily have to come up with a telaprevir resistant strain "on the fly" in order to survive after the anti-viral onslaught initiates in all patients. Many patients were tested for PI/telaprevir resistant virus prior to being given telaprevir (and other PI's), and in a fair number of them either a partially or wholly resistant virus was found to already be in existence (albeit in very small numbers). So the mechanism for survival in the face of a PI attack wouldn't necessarily always be a purely adaptive one borne of a ferocious rate of mutative iterations and managing to come up with that "one in a trillion" just in the nick of time during the onslaught. It could simply be a case of the non-resistant variants being wiped out, and the very few pre-existing resistant types simply moving in and taking over (especially in the case of PI monotherapy). That is unless there are mutliple anti-viral modes of efficacy in play to keep this from happening, as in VX+SOC.
yes, development of an effective immune response to the various "efficient" forms of the virus is the negotiation I believe is at the heart of SVR. I think of each tx as a sort of rerun of "High Noon" - after 48 (or 72) weeks of hell the streets are deserted. All that's left is a few surviving virions (black hat) and the DC and lymphocytes (white hat), just like at the time of the original acute infection. This time will the guy with the white hat (finally!) manage to get his act together or will the banditos run amok all over town once more? and so the story continues. HR's summary of the mechanics of T cell activation in that vaccine thread doesn't bear improving on - check it out.
Also, re your question about the relative damage done to the virus by vertex vs soc unnfortunately I don't believe there's an answer. The virus' greatest strength is an error-prone way of making copies of itself (there's some deep philosophical insight here about the fundamental importance of change) and this error rate per virion is pretty much constant. If you could knock off enough of the total virus quickly enough there might be so few survirors left they might not be able to find the necessary escape mutation in time. For vx this doesn't seem to be the case, within a few weeks the survirors have found the way out - but possibly with other drugs. How quickly is quick enough isn't known as best I can tell. In principle the simple but effective models used to predict the virus' steady-state population could be adapted, but I don't believe this has been done.
Also, re your question about the relative damage done to the virus by vertex vs soc unnfortunately I don't believe there's an answer. The virus' greatest strength is an error-prone way of making copies of itself (there's some deep philosophical insight here about the fundamental importance of change) and this error rate per virion is pretty much constant. If you could knock off enough of the total virus quickly enough there might be so few survirors left they might not be able to find the necessary escape mutation in time. For vx this doesn't seem to be the case, within a few weeks the survirors have found the way out - but possibly with other drugs. How quickly is quick enough isn't known as best I can tell. In principle the simple but effective models used to predict the virus' steady-state population could be adapted, but I don't believe this has been done.
I wish I could tell you of what else might have worked, certainly if your rash was to the anaphylaxis stage probably nothing else would have, but you didn't say that at first.
Don't know what the current thinking is, having not kept up on the reactions field, at one time I had to.......but it used to be no steroids for folk under 80, when the first liver studies came out.
I had chosen to forego steroids in my 20's even with raw grapefruit sized patches on my skin, based solely on the reports of liver damage.....so even then I was "being careful" as I could be.
I know that whole bad rap is much underplayed now, and certainly people want relief, but the public at large I do not think know, nor are they warned as to how cummulative steroid damage is to the liver.
Even though, when you think about it, with all the athletic abuse it should be common knowledge.
Of course if your rash was bringing lots of fluid to your skin surface, that means it could also swell your throat and make your heart stop...in those cases what's worse is thrown out, it's what will stop the allergic reaction in time to save life, and darn the torpedos. I've been there too.
I guess I was questioning, only based on your veriage of "bad rash". Obviously there's bad, and then there is BAD.
Don't know what the current thinking is, having not kept up on the reactions field, at one time I had to.......but it used to be no steroids for folk under 80, when the first liver studies came out.
I had chosen to forego steroids in my 20's even with raw grapefruit sized patches on my skin, based solely on the reports of liver damage.....so even then I was "being careful" as I could be.
I know that whole bad rap is much underplayed now, and certainly people want relief, but the public at large I do not think know, nor are they warned as to how cummulative steroid damage is to the liver.
Even though, when you think about it, with all the athletic abuse it should be common knowledge.
Of course if your rash was bringing lots of fluid to your skin surface, that means it could also swell your throat and make your heart stop...in those cases what's worse is thrown out, it's what will stop the allergic reaction in time to save life, and darn the torpedos. I've been there too.
I guess I was questioning, only based on your veriage of "bad rash". Obviously there's bad, and then there is BAD.
Well the steroids I was on were pretty strong, especially the bolus solumedrol (that's what they give people in the ER that are having potentially lethal allergic reactions to bee stings etc). And to my knowledge prednisone can be a very potent immunosuppressant, it just depends on what dose you take (and 80mg/day is a lot). So I don't know what immunosuppressants would have been better or more effective than these for controlling my runaway rash. Also, of course both me and my doctor did not want to overdo immunosuppressants considering I was knee deep in tx and a steroid jamboree could have nixed my SVR for good. So as far as I know what they gave me was what would commonlpy be used for that sort of thing. Why, do you think another type of immunosuppressant would have been better?
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