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Anyone know the dynamics of relaspe?
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Anyone know the dynamics of relaspe?

If one has done the ultra sensitive PCR <2, my understanding is that  that precludes the possibility of a very small remnant of viron living in the serum, that after tx might repopulate. So the relasping viron would be hiding out in the liver I suppose. Is a damaged liver eaiser to hide in? Why? jerry
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Avatar_n_tn
Virus does not 'hide' as such-it mutates.
The dynamic of relapse is that a so called 'wild type' variant designs itself during treatment and survives in small numbers only to reproduce prolifically when treatment ceases.
Whilst it is true that a scarred liver is a negative predictor for treatment success the virus relies on healthy liver cells which it uses for 'factories' in which to replicate.The T-Cells that we produce to deatroy  infected cells are blood borne which may be why a compromised flow through the liver can impede an SVR
I know that this is a rather simplistic attempt at an explanation but it goes some way to explaing why a patient can be undectable on treatment for upto a year yet still relapse.
Protese inhibitors such as Telaprevir specifically prevent the design of a successful wild type variant as the Vertex company has explained in their presentations.
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Avatar_m_tn
The virus replicates very quickly 10 to the 18th. Which means each day one trillion new virons are created. So if there are even the smallest amt remaining it will become dedectable quickly.
Red
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Avatar_m_tn
HCA

'wild type' variant

Its my understanding that 'wild type' refers to established genotypes. A wild type variant would be a quasi-species.

Red--  "replicates very quickly 10 to the 18th "

This illustrates just what a fantastic job our immune system does in keeping vl relatively low. Even so, many of these replicons are quasi-species that will exist only a short period of time even without an attack from our immune responses. This is due to their instability,which is a product of translation errors by error-prone RNA.

Mr Liver
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Avatar_n_tn
Yes, the use of 'variant' may be misleading

Boger of Vertex actually said
'The model revealed that the mutant species of the virus were constantly present, and provided an explanation for why the virus would return even when the viral load was undetectable. The model also predicted that if Telaprevir could knock out the wild type of the virus very quickly, follow-up with the current drugs could remove the remaining mutant species, successfully curing the disease'
For those interested the full text is here;
http://www.bio-itworld.com/2008/05/09/boger-keynote-bioitworld-expo.html
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186344_tn?1278268245
"The model also predicted that if Telaprevir could knock out the wild type of the virus very quickly, follow-up with the current drugs could remove the remaining mutant species, successfully curing the disease."

Does not this mean that Telaprevir knocks out the original wild type virus, and then interferon and ribavirin removes the remaining mutant species created by the use of Telaprevir? That is how I have understood it.
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186344_tn?1278268245
Should read "the remaining mutant species created by the use of Telaprevir and SOC".
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186344_tn?1278268245
"Protease inhibitors such as Telaprevir specifically prevent the design of a successful wild type variant...."

The way Telaprevir would be helpful would be because of its quick eradication of the wild type virus which gives the virus less time to find an efficient mutant species that can survive the attack of the immune system enhanced by interferon and ribavirin.

Feel free to correct me if I am wrong. I am just a layman.
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Avatar_n_tn
That is approximately my understanding.
The knowledge I have is gleaned from the internet and not debated with others (apart from my doctor occasionally) so any misconceptions I may have are not really challenged..
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186344_tn?1278268245
I've also understood it to be that when not treating the wild life virus tends to choose variations which allow it to reproduce as much as possible. Depending on how strong one's own immune system is, one will have either a high or a low viral load when not treating. During tx the virus instead tries to mutate into quasies which allow it to survive tx. If we want to, we can call this "to hide" from tx.
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186344_tn?1278268245
Since telaprevir attacks the virus directly, time is precious, because the virus will find a quasi form which is resistant to telaprevir. Then our immune system has to do the job with the help of interferon and ribavirin to eradicate the remaining virus.

If relapse occurs after treating with telaprevir and SOC, the virus will once again go back to the wild life forms which allows it to replicate as much as possible, but it will retain in its "memory" the resistance against telaprevir, which is why one does not treat twice with these new drugs.
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186344_tn?1278268245
wild life virus = wild type virus
LOL
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