Aa
Hepatitis Researcher, Pre-Dosing Ribavirin
I am starting treatment with Infergen in 2 weeks and am planning on pre-dosing riba(1,600 daily) leading up to the start date. Do you feel this may give me an edge or would it be better to just add the extra riba to the daily intake once I start the Infergen?
MO: I'm his opinion on pre dosing with riba and he said it was "VooDoo.
----------------------
LOL. I assume it's the "Rock Star" I'm familiar with? Curious though, can you tell us who "Donovan" is. I ask because very little on pre-dosing within the medical community and might be worthwhile knowing what he knows. Just mostly us here with our voodoo dolls :)
-- Jim
----------------------
LOL. I assume it's the "Rock Star" I'm familiar with? Curious though, can you tell us who "Donovan" is. I ask because very little on pre-dosing within the medical community and might be worthwhile knowing what he knows. Just mostly us here with our voodoo dolls :)
-- Jim
I was hoping to pre dose ( I still might) and I went for another consult - a "rock star" and asked him his opinion on pre dosing with riba and he said it was "VooDoo." So I guess that means he's not impressed:) He just doesn't buy into it at all.
He used another doctors name and said "that's Donovan" < not real doctors name ,,,and I said "no, I haven't discussed this with him yet, I forgot, but I will the next appointment." He thought I got the "pre dose" idea from that particular doctor. I wouldn't tell him that I heard it here. I've made that mistake before(saying I get good info from MH) and I get "the look", but I give ~the look~ right back.
Good luck with whatever you decide.
I have no choice but to tx now cause all these doctors have said that there is nothing around as far as new drugs for geno 2's - and being I am a geno 2 'relapser,' I would be waiting even longer for studies to be done he said. But I figured that, and thats why I call myself " a minority within a minority," - not too many geno 2 relapsers out there:)
Kind of stinko when I really think about it, but at least I am feeling good these days and I am thankful for that.
He used another doctors name and said "that's Donovan" < not real doctors name ,,,and I said "no, I haven't discussed this with him yet, I forgot, but I will the next appointment." He thought I got the "pre dose" idea from that particular doctor. I wouldn't tell him that I heard it here. I've made that mistake before(saying I get good info from MH) and I get "the look", but I give ~the look~ right back.
Good luck with whatever you decide.
I have no choice but to tx now cause all these doctors have said that there is nothing around as far as new drugs for geno 2's - and being I am a geno 2 'relapser,' I would be waiting even longer for studies to be done he said. But I figured that, and thats why I call myself " a minority within a minority," - not too many geno 2 relapsers out there:)
Kind of stinko when I really think about it, but at least I am feeling good these days and I am thankful for that.
willingquote: “My point was only that there is no known reason to believe that starting riba before ifn has a beneficial effect.”
We may not have any scientifically proven reason (yet, anyway) to believe that pre-dosing riba will enhance anti-viral kinetics (and subsequent SVR rates), but we have a quasi-plausible theory that it just might help (including FLGuy’s anecdotal report of going UND in 2 weeks with a starting VL of 4 mil with cirrhosis). As is often the case in HCV treatment, especially for those in tough to treat scenarios, we must make decisions based on limited and imperfect evidence (as is the case for alinia right now). The way I see it, if the proposed “off-label” strategy does not introduce an unreasonable level of risk and the suspected/hoped for benefit is meaningful, then it’s reasonable to implement and include that strategy (be it IFN doubledosing, alinia, riba predosing etc). In the case of riba predosing, I think it rises to an actionable level and the risk is usually manageable (especially with pre-emptive procrit onboard). As far as the previously mentioned lag between serum levels and possibly referred immune responses, effectively all this means to me is letting the serum levels come up to strength and then letting them “season” at those levels for maybe a week before starting the IFN – with total predosing duration maybe lasting 2-3 weeks (4 on the outside) depending on how convinced I was serum levels ramped up quickly. In the event that little sub-theory turns out to be hogwash, then not much harm done, especially when the totality of a 48 wk (or more) tx is factored in. Bottom line is that if I were entertaining starting an SOC based tx anytime soon, I’d incorporate riba-priming into my treatment. Out of curiosity, what would you do?
willingquote: “We do however know that riba serum concentration bounces around for the first two weeks and thus that most patients go through their first-phase VL decline without having reached steady state concentration.”
That’s interesting to hear that it bounces around for the initial 2 weeks, I didn’t know that. I would think there would be a fairly steady increase to full strength levels over the course of a few weeks. Is it understood why this happens? And if what you say above is true concerning patients undergoing their most profound viral decline while their riba levels are fluctuating (presumably up and down?)…then might this also suggest that predosing riba and equilibriating it to steady levels (full strength) prior to the introduction of IFN might pay dividends?
willingquote: “In fact, along the lines of open speculation I think there's more support for continuing riba post-EOT. Per the CTL epitope theory, as substantiated by that "shortens the half-life of infected cells" quote above, there may be reason to believe that continuing riba post eot may expose the relapse-inducing virions that remain in infected cells at eot.”
That’s interesting, never heard that one before (at least in the absence of extending IFN too). I know HR had discussed the theory for IFN dose tapering after EOT, mostly as a way to allow the body’s own IFN production/modulation to come online instead of simply shutting off the synthetic IFN faucet cold turkey. Also, I would think the speculated effects of riba you describe above would occur anyway for some time after EOT considering its long half-life. One thing’s for sure, when I finally quit riba I was glad to see it go!
We may not have any scientifically proven reason (yet, anyway) to believe that pre-dosing riba will enhance anti-viral kinetics (and subsequent SVR rates), but we have a quasi-plausible theory that it just might help (including FLGuy’s anecdotal report of going UND in 2 weeks with a starting VL of 4 mil with cirrhosis). As is often the case in HCV treatment, especially for those in tough to treat scenarios, we must make decisions based on limited and imperfect evidence (as is the case for alinia right now). The way I see it, if the proposed “off-label” strategy does not introduce an unreasonable level of risk and the suspected/hoped for benefit is meaningful, then it’s reasonable to implement and include that strategy (be it IFN doubledosing, alinia, riba predosing etc). In the case of riba predosing, I think it rises to an actionable level and the risk is usually manageable (especially with pre-emptive procrit onboard). As far as the previously mentioned lag between serum levels and possibly referred immune responses, effectively all this means to me is letting the serum levels come up to strength and then letting them “season” at those levels for maybe a week before starting the IFN – with total predosing duration maybe lasting 2-3 weeks (4 on the outside) depending on how convinced I was serum levels ramped up quickly. In the event that little sub-theory turns out to be hogwash, then not much harm done, especially when the totality of a 48 wk (or more) tx is factored in. Bottom line is that if I were entertaining starting an SOC based tx anytime soon, I’d incorporate riba-priming into my treatment. Out of curiosity, what would you do?
willingquote: “We do however know that riba serum concentration bounces around for the first two weeks and thus that most patients go through their first-phase VL decline without having reached steady state concentration.”
That’s interesting to hear that it bounces around for the initial 2 weeks, I didn’t know that. I would think there would be a fairly steady increase to full strength levels over the course of a few weeks. Is it understood why this happens? And if what you say above is true concerning patients undergoing their most profound viral decline while their riba levels are fluctuating (presumably up and down?)…then might this also suggest that predosing riba and equilibriating it to steady levels (full strength) prior to the introduction of IFN might pay dividends?
willingquote: “In fact, along the lines of open speculation I think there's more support for continuing riba post-EOT. Per the CTL epitope theory, as substantiated by that "shortens the half-life of infected cells" quote above, there may be reason to believe that continuing riba post eot may expose the relapse-inducing virions that remain in infected cells at eot.”
That’s interesting, never heard that one before (at least in the absence of extending IFN too). I know HR had discussed the theory for IFN dose tapering after EOT, mostly as a way to allow the body’s own IFN production/modulation to come online instead of simply shutting off the synthetic IFN faucet cold turkey. Also, I would think the speculated effects of riba you describe above would occur anyway for some time after EOT considering its long half-life. One thing’s for sure, when I finally quit riba I was glad to see it go!
It's always nice to see your name here - and to read your thoughts too. Be well, Mike
tn: will do. BTW, re ntz, among the many things that remain to be shown is whether its effect on relapsers/nonresponders is significant. As far as I know, what's been released about its mechanism of action is "selectively inhibiting dephosphorylation of eukaryotic initiation factor 2α (eIF2α)". In the context of anti-viral effect, phosphorylation of that initiation factor is done by the PKR kinase in response to ifn-alpha receptor binding on the cell membrane (normally part of the "spraying the neighborhood" effect as HR described it). One of the tools in hcv's bag of tricks is a domain on its E2 protein, the PePHD domain, that may inhibit this action allowing an infected cell to happily keep translating its mRNA in the presence of ifn. Regardless, ntz's mechansism of action seems to be closely correlated to ifn's. In fact, for the data released at aasld, SVR among the tx-experienced arm, 36%, was much less impressive than the 93% among the tx naive.
mremeet : OK, there may well be other riba dosing strategies that work better than co-administration per current soc but that remains open speculation in the absence of any evidence. My point was only that there is no known reason to believe that starting riba before ifn has a beneficial effect. We do however know that riba serum concentration bounces around for the first two weeks and thus that most patients go through their first-phase VL decline without having reached steady state concentration.
In fact, along the lines of open speculation I think there's more support for continuing riba post-EOT. Per the CTL epitope theory, as substantiated by that "shortens the half-life of infected cells" quote above, there may be reason to believe that continuing riba post eot may expose the relapse-inducing virions that remain in infected cells at eot.
mremeet : OK, there may well be other riba dosing strategies that work better than co-administration per current soc but that remains open speculation in the absence of any evidence. My point was only that there is no known reason to believe that starting riba before ifn has a beneficial effect. We do however know that riba serum concentration bounces around for the first two weeks and thus that most patients go through their first-phase VL decline without having reached steady state concentration.
In fact, along the lines of open speculation I think there's more support for continuing riba post-EOT. Per the CTL epitope theory, as substantiated by that "shortens the half-life of infected cells" quote above, there may be reason to believe that continuing riba post eot may expose the relapse-inducing virions that remain in infected cells at eot.
Thanks for the greeting - and great to see you, too!
If you get the chance, fire me off an e-mail (if you still happen to have mine floating somewhere). My entire contact list when "poof" a couple of months ago when Micro-squish asked me to "update" Windows Live Mail. Still trying to recover from that "helpful" upgrade.
TnHepGuy
If you get the chance, fire me off an e-mail (if you still happen to have mine floating somewhere). My entire contact list when "poof" a couple of months ago when Micro-squish asked me to "update" Windows Live Mail. Still trying to recover from that "helpful" upgrade.
TnHepGuy
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.
