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Hep C Discussion Forum -> Hep C News -> CROI 2016: Viral Hepatitis and Liver Fibrosis
Post Info TOPIC: CROI 2016: Viral Hepatitis and Liver Fibrosis
Pablito


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RE: CROI 2016: Viral Hepatitis and Liver Fibrosis
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I indeed remember reading Malcolm's thread on the topic.  A man with much knowledge!



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44 y.o. male, HCV G4 since 1996, F-scan score 9, F2, Failed prior I/R, finished sof/vel/vox 8 weeks 5/16, pre-treatment VL 2 million, EOT UND, EOT+4 UND, EOT+12 UND.
RAGDOLL


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 Tig,  Great information.  Thanks CC



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F 63,  1b  1974, no cirrhosis, fibro scan 5.8 F0-F1,fibro test .37 ,V/L 702987, ALT 90, AST 75.  ABBVIE Topaz II on 10-30-14 Viekira Pak no RIBA , EOT 1-22-15 SVR, ALT 37, AST 29, 4-15-15 SVR12 - fibro test .22,  1-21-16 SVR 52 ,  1-21-17 SVR 104! 1-21-18 SVR 3 years ,2020 5 years, 2022 7 years!
Tig


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Hey Pablo,

The subject of RAV's is quite a topic and has been a constant source of discussion here. I remember when they weren't even talked about. When the NS3/4 inhibitors came along, the failures were further studied and R&D started seeing the relationship these variants had on SVR rates. It has continued with the NS5A/B's. They keep finding a more powerful drug or a weaker link in the RNA to break. Sovaldi is an extremely effective drug that has proven it's effectiveness with just about everything. Backbone is an accurate term, it supports just about everything. Gilead has a goldmine there.

I like your interpretation. We have had several discussions on RAV's. Malcolm has posted several items here on the subject that explain some of this well. Matt Chris has as well. Use the search function and if I can help you with anything, let me know.

I like the prospects of Sov/Vel/Vox too, even Sov/Velpa (Epclusa) is a great new comer as well. Then we have further study by Merck, BMS, Abbvie and others that will continually change and likely improve effectiveness and treatment length in the near term. If I were to guess anyway. Look at what we've witnessed in the last 2 years. I'm liking what I'm seeing. They're coming so fast, it's hard to stay on top of all the research.

 



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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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Pablito


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The section on RAVs is particularly good and has added greatly to my understanding.  I attach the table Canuck posted a while back here as I think it feeds in nicely to this paper.

My understanding is this: sofusbuvir (and other NS5B inhibitors) are potent DAAs with a high barrier to resistance and are, hence, the backbone of treatment regimes.  They do the heavy-lifting work, but they are not quite potent enough to get us over the line and, as such, are never used as a mono-therapy.

NS5A inhibitors, on the other hand, are highly potent DAAs but are prone resistance,  For people without cirrhosis and, in particular, no NS5Bs RAVs 12 weeks of Harvoni (or similar) should achieve SVR rates close to 100%. But it's these pesky NS5A RAVs that are causing treatment failures.  Further, these RAVs are more common in G1 and G3 and, hence, why these genotypes have lower SVR rates.

But hope if not lost, as the paper says that re-treatment with 24 weeks of Harvoni gave 89% SVR rates in prior treatment failures so somehow longer treatment can overcome RAVs....presumably the longer exposure to sofosbuvir is enough to get people with RAVs over the line.  Then there was something that I hadn't heard before: RAVs differ in potency with some reducing the concentration of NS5As ten-fold but others up to a 1000-fold.  So maybe if the RAV is on the weaker end of the spectrum the extra 12 weeks of the NS5A is helping out its friend sofosbuvir too.

There's the option of adding in ribavirin too.  And then we have the new triple therapies, like sof/vel/vox, the NS5B/NSRA/protease inhibitors combos and other novel treatments.

It's all starting to come together in my mind.  Have I got this right?

Pablo



-- Edited by Pablito on Saturday 23rd of July 2016 05:05:36 PM

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44 y.o. male, HCV G4 since 1996, F-scan score 9, F2, Failed prior I/R, finished sof/vel/vox 8 weeks 5/16, pre-treatment VL 2 million, EOT UND, EOT+4 UND, EOT+12 UND.
Pablito


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Lots of high quality data there, Tig.



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44 y.o. male, HCV G4 since 1996, F-scan score 9, F2, Failed prior I/R, finished sof/vel/vox 8 weeks 5/16, pre-treatment VL 2 million, EOT UND, EOT+4 UND, EOT+12 UND.
Tig


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More information from the Conference on Retroviruses and Opportunistic Infections (CROI) 2016. In PDF format and technical, but is very informative and separated into easy to find subjects that may be of interest to you. 

Viral Hepatitis and Liver Fibrosis



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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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