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Post Info TOPIC: Ribavirin's impact on Polymorphisms / RAV's during Treatment


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RE: Ribavirin's impact on Polymorphisms / RAV's during Treatment
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Hi Matt,

I doubt whether you'll ever find an exact answer to the question of Ribavirin's mechanism of action. As you said, Riba is most potent in it's triphosphate form, and it is a weak NS-5B inhibitor of many viruses. It also has some action at NS-5A. This old article is one of the best:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099343/

There is no real difference between population and deep sequencing for RAV's. Previously population sequencing referred to the percentage population of a certain mutation in the total quasispecies count eg 3%.

We are waiting for further info concerning the NS-5A RAV's in particular. In Merck's C-SALVAGE Trial, the Merck duo (including Elbasvir) had a 75% SVR rate when Y93H was present at baseline. The time for these RAV's to decay is not known. Patience mate. Cheers.



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Geno 1b, IL28B CT,  x3 prior relapser,  ex-cirrhotic, 75 yo, did 48 weeks with Victrelis/Peg./Riba.  VL 1.28m at start, UNDET. at 8 ,12 ,16 ,24 ,30  and 48 weeks.  EOT 15 Feb 2013 , UNDET. at EOT + 28 weeks. SVR!  Still Undet. at EOT +5 years

Malcolm



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Matt, thanks for sharing this.  I discussed adding Riba to the Harvoni with my doc prior to start of Harvoni tx in November, and again partway through my 24 weeks.  She used the "only 2%" logic in not prescribing it.  Praying it works out.  I had previously sent her the link where doc's from the AASLD conference in Boston were discussing the benefits of adding Riba to Harvoni but it didn't help.  This is a teaching hospital and one would expect they use the best protocols.  Still, in relative terms this is all very new.  My 4 week labs need to come back UND.  Guess I'll know the first week in June.  Take care.



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1b  Int/Riba relapse @ 48 weeks.  Stop tx Peg Int/Riba 12 weeks ill. Relapse S/O 6/23/14 :(   Started Harvoni 11/12/14  EOT 4/28/15.  EOT+4 UND :)  SVR! 8/4/15  :)     Thankful for every morning.



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I signed up for a HCV webinar sponsored by Clinical Care Options with Mark S. Sulkowski, Professor of Medicine from Johns Hopkins University School of Medicine Baltimore, Maryland

One of the topics was · Role of Resistance Testing in HCV Re-treatment 

During the program Dr. Sulkowski said a statement that the addition of Ribavirin helps to control HCV polymorphisms / Rav's from emerging during treatment. I thought I have heard that before but I never seen a scientific research written about its use with the new DAA's. I googled the internet but found no up to date info. other than the SVR results from the ION trials where the addition of Ribavirin increased the percentage by 2% of percentage points in the 24 week arm and 4% in the 12 week arm.

Here is the link   http://www.natap.org/2015/EASL/EASL_87.htm

My deeper question has to do with how and where Riba impacts HCV polymorphisms is it mostly add the NS5A or other parts? Has anyone on the forum read or found any new data on ribavirin with the new DAA protocols?

I did find this older article about Riba when the SOC was Interferon & Riba that provided some interesting insight   

Ribavirin is a broad-spectrum antiviral nucleoside analogue that is converted to mono-, di- and triphosphorylated forms inside of cells. It has recently been demonstrated that the antiviral activity of ribavirin can result from the ability of a viral RNA-dependent RNA polymerase (RdRP) to utilize ribavirin triphosphate and to incorporate this nucleotide into the viral genome with reduced specificity, thereby mutagenizing the genome and decreasing the yield of infectious virus.[6] Moreover, ribavirin exhibits an antiviral effect through a mechanism of error-prone replication in the HCV subgenomic replication system.

I did submit two questions for the webinar that was not answered.

#1 what is the difference between "Population Sequencing" and "Deep Sequencing" 

#2 once patient has developed a RAV at a particular address like NS5A location Y93H in GT1a scenario can they be treated with a newer DAA's that covers that resistance address with no problems?  

I know this is deep stuff but it needs to be answered sometime in the future.

matt

 



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"And in the end, the love you take is equal to the love you make"

61 year old Geno type A1, F4 Cirrhotic, started 24 weeks on Harvoni 12-17-14 ,EOT-5 week = UND, 8-31-15 =UND , SVR-24 Baby YES! 

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