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Hep C Discussion Forum -> General Discussion -> Yet another post about RAVs!
Post Info TOPIC: Yet another post about RAVs!
Zlikster


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RE: Yet another post about RAVs!
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Tnx Malcolm,

Is there a test to check mysterious Riba levels in blood while on tx? My hepa was telling me, more toxic, the better (when looking at hgb/rbcc levels). Since i am gonna get again some Riba love soon, wondering will it be in vain again cause i might not be absorbing it well. Since my last time on tx there wasn't much "riba toxicity" until 4th month of tx. Really strange that molecule like Ribavirin (which has been discovered 40 years ago?) and it's antiviral mechanism is still poorly understood...wondering whats holding up it's derivatives like Taribavirin from finishing clinical trials.

best



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GT 3 dg. 08-2012 / FibroScan: 5 kPa F1 / FibroTest: F0-1 A1 / SoC TX: PegInt 120mcg+Riba 1000mg UND from w8 relapse EOT+4w
01-2016 Sof+Dac+Riba UND from w8, SVR24!
Groupergetter


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Thanks Malcolm, good discussion.  I have twice asked my physician about adding riba to the Harvoni (prior to and during tx) She chose not to prescribe. Hope this was the right decision.  We're thankful you are here.   Be well



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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.
mallani


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The question whether Ribavirin is needed in some cases is just too complicated.

Although it mops all ALL RAVs, there is an understandable reluctance to prescribe it. Also some patients don't seem to be able to absorb it and get the right blood levels.

For the 1a's, until better drugs are approved, it adds some insurance.



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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
Matt Chris


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Hey Malcolm

Good common sense approach to the HCV polymorphisms, its really shows the years progression of DAA's and their control of the different mutation addresses. Like you said, in time its likely that that the newer DAA's will be able to suppress nearly all the sites. 

The more I learn about how the HCV reacts to DAA's the more I see the importance of big Pharma get this right. I am wondering if an additional item/drug is needed along with the (DAA's) replication / inhibitors blockers to help the immune system clean up the remnants of HCV.

Something like interferon or Riba but not as toxic. 

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! 
Miss B


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Malcolm,

Thank you so much! This is very interesting info.



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Miss B
56 years old. Genotype 1B, previous treatment with interferon 1994. Started Harvoni 12/8/14. After 2 weeks, VL dropped from over 4 million to 496. At 4 weeks, undetected, but at 8 weeks, <15 mL (detected), at 12 weeks/EOT UND!  
Tig


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Thank you Malcolm, an excellent explanation! Many thanks to your colleague for sharing his time and knowledge on this important topic.

Tig



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Tig

68yo GT1A - 5 Mil - A2/F3 - (1996) Intron A - Non Responder, (2013) Peg/Riba/Vic SOT:05/23/13 EOT:12/04/13 SVR 9+ years!

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mallani


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Hi all,

I've just spent some time talking to a Virologist at the PA Hospital Liver Unit. I've cancelled a lot of my on-line subscriptions and wanted to be sure I haven't missed anything.

The whole topic of RAVs (Resistant Mutations) is still poorly understood. The antiprotease RAVs have been discussed at length previously.

The NS-5A site is now the most discussed. This is an unstable site, particularly in Geno 1a's. For an unknown reason, patients with a non-CC allele at IL28B don't do as well. With the first generation inhibitors (Daclatasvir, Ledipasvir and Ombitasvir), RAV's quickly developed and in fact, many were present before treatment. The next generation NS-5A inhibitors, GS-5816 and Elbasvir (MK-8742) have been found to be effective against these RAVs, and will obviously be important in retreatment of any relapsers ( particularly for Harvoni or ViekiraPak).

Unlike the antiprotease RAVs, these NS-5A RAVs appear to be 'fit' and can exist for a long time. None of the RAVs appeared when Sovaldi was present- they only surface after EOT. It is important to remember that an Undetected Viral Load result just means no virus can be detected in the peripheral blood. There may still be virus in blood monocytes, liver cells and virtually any other tissue.

The non-nucleoside blockers of NS-5B have also been investigated. These are very unstable and apart from Dasabuvir (in ViekiraPak), I can't see any use for them.

In the PAH Trials, ALL patients were Undetected at the end of a Sovaldi treatment (i.e. Sovaldi/Riba, Sovaldi/Peg/Riba and Sovaldi/Daclatasvir). In the few that relapsed, they did so in the first 6 weeks after EOT. So obviously RAVs to Sovaldi must exist, and the fact they can't be found must mean they are transient, and quickly revert back to wild-type virus.

Pretreatment testing for RAV's will never happen. It's too expensive and nobody knows what the results mean. At the moment, testing of relapsers is useful but the results can be predicted and it doesn't change anything.

What we need to do is wait for the newer generation drugs to be approved. Then, SVR rates will be close to 100% and RAVs won't need to be mentioned.

Again, I urge all new patients to insist that their doctors do a proper liver assessment prior to treatment (biopsy or Fibroscan). At the moment, 8 weeks of treatment for an F3 or F4 may result in heartache. 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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