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beaches said: “I thought that HCV mutated quickly anyway,and that’s what made it so hard to treat.”
Yes. Here is a good read on mutants and resistance that Dr James wrote last year.
To answer Enkel’s question at the end, Sofosbuvir has a high barrier to resistance. It can happen but is uncommon.
G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
Meg wrote:Very interesting thread!
Tweakmax you wrote : ” But would there be resistance e.g. worst case is sofosbuvir resistance at position S282T, then it will definitely affect future treatments as sofosbuvir is still the backbone for HCV treatment/retreatment
” .Does it mean that longer treatments with sofosbuvir may cause the Hep C virus to become resistant to it? What comes to mind is when treating G1b – no cirrhosis – tx naive – low VL it would be the ideal to treat it with 8 weeks instead of 12 weeks following Gilead’s guidelines. Because if there is a relapse – and 5 % will relapse anyway no matter how well patients follow any specific tx (it is a matter of statistics) there is smaller chance to become resistant to sofosbuvir on a 8 week tx than on a 12 week tx. Right?
Must ask the doc haha
What I know is, those on a 8 week tx, if relapsed, have a good chance of curing if do the tx longer the second round!
If I were u, I will just do the normal 12 weeks. 8 weeks is too risky really. But it is your personal choice
Hi Meg,
I’m not an expert but I suspect the answer to your question is basically no and the main reason for shorter treatment is economic (see the second half of post#797 of this link https://fixhepc.com/forum/resistance/164-resistance-and-treatment-failure-mechanisms.html?limitstart=0#797) plus a small desire to reduce length of exposure which is a worthy aim with any drug as long as the Tx is effective.
We need to remember that we can’t be completely certain before treatment how much fibrosis and other liver damage is present in a patient. Also viral load levels are based on how much RNA can be detected in serum, they do not reflect how many hepatocytes are infected. So when Gilead say that 8 weeks harvoni Tx is suitable for low fibrosis, low viral load 1b patients they are really saying “on average to achieve an acceptable SVR rate”.
Also the 95% SVR rate you talk about for 8 weeks harvoni Tx will actually increase to something like 99% if 1b patients are given 12 weeks Tx.
We know that failing treatment is often an indicator of some form of resistance, that is why we repeat Tx with a longer, stronger dose or different drug the next time. So presumably the shorter 8 week Tx results in increased risk of resistance developing compared with longer treatment for the maybe 4% or so extra patients who fail on shorter Tx.
As far as Sofosbuvir S282T resistance goes, it is extremely rare both at baseline and in those who develop viral failure per below quote and is not very good at replicating if it does occur.
In another recent pooled analysis of phase 2 and 3 studies where sofosbuvir based regimen was administered, no S282T variant was detected at baseline. Emergence of this variant was infrequent (1%) in subjects who had virlogical failure. S282T levels declined on average by four fold within two weeks of follow up period confirming low replication fitness of this variant [61].
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690891/
So in most cases any resistance that develops in those who don’t reach SVR during standard Tx will be to something other than Sofosbuvir and that takes us back to Dr James post at the top of the thread.
G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
Hi Gaj thank you so much for explaining how Sofosbuvir S282T resistance goes and how rare it is to become resistant to Sofosbuvir. Phew! I had no idea. Also have been biased all along by “the desire to reduce length of exposure which is a worthy aim with any drug as long as the Tx is effective” . I have missed this other very important piece of information too that “the 95% SVR rate we talk about for 8 weeks harvoni Tx will actually increase to something like 99% if 1b patients are given 12 weeks Tx.” ! This is fantastic!
hmy: As far as I had understood so far it was just about 1% increase. Lastly I had no idea either that a 8 week tx could in fact increase the risk of resistance comparing to a longer tx. Live and learn everyday!
Thanks again Gaj.
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