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1084115 tn?1385232189

how does triple tx working

o.k maybe its a strange question but i want to ask.

iam in triple tx with inc.

the first 12 weeks i had triple dosing, and try to get UND as early as possible.
so,when your UND by week 4 and 12 the incivek is finished and the peg and riba have to do their job.

when your UND at week 12 and continue with soc,do they supress the virus or whats their job exactly for the rest of therapy?

regards
3 Responses
2062453 tn?1350336542
Hi Rexx:

I'm 8 weeks further along from where you are in treatment -- I just started week #22 of triple therapy (Incivek).

I'm not a researcher or a doctor, but I will tell you what I THINK the peg and riba are doing for ME.

I think peg and riba are boosting my immune system. I think the peg and riba are helping my body eradicate any of the virus that remained after the protease inhibitor (Incivek) worked it's magic.

I also believe there (unfortunately) is small chance the peg and riba are keeping my virus in hiding -- that's what I believe happened to me in 2009 when I went from UND to 1.8M VL within a month after stopping soc. If the same thing is happening again, I believe the peg and riba will keep my virus in hiding until I stop soc in 3 weeks.

Because of what happened to me in 2009, this time I requested my doctor conduct a VL test 2 weeks after I stop treatment. Based on my 2009 experience, I believe 2 weeks will be enough to determine if the virus had been in hiding during treatment. In addition to this 2 week post treatment VL test, I'll also get the standard 4 week post treatment VL test and the 6 month VL test.

Maybe someone else will respond with a more technical answer to your question.

Regards,
GB
1815939 tn?1377995399
I found some links that will tell you exactly how each works. I included only one part of each article and it would probably be benficial to read the entire articles:

Incivek
"Telaprevir is an inhibitor of the HCV NS3/4A serine protease, necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication. In a biochemical assay, telaprevir inhibited the proteolytic activity of the recombinant HCV NS3 protease domain with an IC50 value of 10 nM."

http://www.rxlist.com/incivek-drug/clinical-pharmacology.htm


Ribavirin: 2012

Mode of action
Hypotheses include:

*ribovarin monophosphate inhibits inosine monophosphate dehydrogenase which results in decreased synthesis of guanosine triphosphate (GTP). GTP is required for translation, DNA and RNA virus transcription and RNA virus replication
*inhibition of capping of viral transcripts
*direct inhibition of viral RNA polymerase by ribavirin triphosphate
*modulation of immune response resulting in a reduction of immune-mediated tissue damage
*ribavirin triphosphate is utilized by viral RNA-dependent RNA polymerase and causes lethal mutagenesis of the viral genome


1815939 tn?1377995399
Oops, submitted it accidentally without the post being finished:

I found some links that will tell you exactly how each works. I included only one part of each article and it would probably be benficial to read the entire articles:


Incivek:

"Telaprevir is an inhibitor of the HCV NS3/4A serine protease, necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication. In a biochemical assay, telaprevir inhibited the proteolytic activity of the recombinant HCV NS3 protease domain with an IC50 value of 10 nM."

http://www.rxlist.com/incivek-drug/clinical-pharmacology.htm


Ribavirin: 2012

Mode of action
Hypotheses include:

*ribovarin monophosphate inhibits inosine monophosphate dehydrogenase which results in decreased synthesis of guanosine triphosphate (GTP). GTP is required for translation, DNA and RNA virus transcription and RNA virus replication
*inhibition of capping of viral transcripts
*direct inhibition of viral RNA polymerase by ribavirin triphosphate
*modulation of immune response resulting in a reduction of immune-mediated tissue damage
*ribavirin triphosphate is utilized by viral RNA-dependent RNA polymerase and causes lethal mutagenesis of the viral genome

http://www.aic.cuhk.edu.hk/web8/ribavirin.htm


Here is an easier to understand article on the mode of action of Ribavirin:

For the treatment effect of ribavirin, mainly three assumptions on treatment mechanisms have been analysed.

Firstly, ribavirin may mainly block viral production. The total effect can be estimated by a viral kinetic parameter describing the treatment efficacy. Nevertheless, this viral kinetic parameter has been estimated comparing the viral kinetics in patients with interferon-α monotherapy and interferon-α plus ribavirin combination therapy (41, 42). If ribavirin mainly blocks viral production, estimated treatment efficiencies on blocking viral production should be higher in patients treated with combination therapy than in patients treated with interferon-based monotherapy. Nevertheless, no significant difference in the efficacy in blocking viral production could be observed but, of course, sample sizes were relatively small and the studies were not powered to detect only slight treatment effects of ribavirin on viral replication.

Secondly, ribavirin may alter the immune response in a way that leads to an enhanced infected cell loss during combination treatment when compared with interferon-α monotherapy. Such an effect would be observable as an enhanced second phase or as a further increase of viral decay after the second phase if the effect will be delayed (41). Indeed, a triphasic viral decline has been observed in clinical data, particularly in patients treated with standard doses of (pegylated) interferon plus ribavirin, and, therefore, such a mechanism of ribavirin can be explained by these models (41, 43–46).

Lastly, ribavirin may influence the infectivity of newly produced virus. This can be modelled by assuming that a proportion of the produced virus is non-infectious and that combination treatment with ribavirin, possibly via lethal mutagenesis, does enhance this proportion (45, 47) [see also (41) for a first sketch of such a model]. Nevertheless, a treatment effect of a second drug on the infectivity during combination treatment can only be observed in patients where the first drug blocks less than about 50–60% of viral production. Therefore, assuming such an effect of ribavirin during combination treatment with interferon fits well with the observation that significant differences in the final phase (second phase in a biphasic decay pattern, third phase for a triphasic decay pattern) were mainly observed in genotype-1-infected patients treated with a standard dose of peginterferon-α but not in patients treated with a high dose of interferon-α (45). Nevertheless, such a model could not explain the strong benefit of adding ribavirin to interferon in the relatively easy-to-treat genotypes 2 and 3 infections (3, 5, 48).

Entire article:
http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2008.01896.x/full


Interferon:

MECHANISM OF ACTION

"Alpha interferons have been extensively studied in the treatment of patients with chronic hepatitis, including hepatitis B, C, and D. Alpha interferons are type-1 interferons and are an important part of the innate antiviral immune response [2,3]. They also play a role in the adaptive immune response. Alpha interferons have potent antiviral activity. They induce interferon-stimulated genes (ISGs) that help establish an antiviral state within cells, though the response is not virus-specific. Alpha interferons act by binding to cell surface receptors, activating a response cascade that culminates in the expression of multiple ISGs, some of which block viral protein synthesis. In addition, alpha interferon may lead to a decrease in viral RNA stability."

http://www.uptodate.com/contents/mechanism-of-action-and-efficacy-of-peginterferon-for-the-treatment-of-chronic-hepatitis-c-virus-infection


Two more links:

http://www.hbvadvocate.org/news/NewsUpdates_pdf/2.2_Conference_Reports/EASL_2002_Agenda/Section3/Thomas.pdf

http://www.atsu.edu/faculty/chamberlain/Website/Lects/Interfer.htm#in


Hope this helps.
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