TOPIC:

Don't take this the wrong way but......sometimes when I read this forum I think people could be forgiven for thinking the DAAs cause certain individuals to LOSE THEIR FUCKING MINDS!

Lighten up, Chester. I thought we agreed we would play the ball not the man.

Or does this restriction apply only to the critics of Prof Gane and not his defenders?

The ball folks, the ball.

"If we don't hang together, we shall surely be all hanged separately"
Benjamin Franklin

M

First to the question of using DAAs prophylactically. I asked this some months back here. You can read the doc's response for yourself.

Thanks. We have an answer! Or at least we have part of the answer to one of the two questions raised in this thread. My understanding is that the Doctor is saying that treatment could be continued indefinitely, or at least beyond 24 weeks, subject to questions of affordability, and possible development of resistance. As to the latter, however, the Doctor is of the view that "this may not be a major issue for a variety of reasons" - as to what those reasons are he does not elaborate.

However, what does remain unanswered is whether sofosbuvir alone would suffice to have this viral suppression effect. This question was not put to the Doctor in the previous thread and so his comments there do not relate to it. But this question is important because it relates to affordability. Generic sofosbuvir alone is, I believe, cheaper than sofosbuvir combined with either ledipasvir or daclatasvir. It may also relate to resistance. The fewer DAAs being taken the less scope for developing resistance.

The fewer DAAs being taken the less scope for developing resistance.

Thurl - this is not true. Monotherapy (with one DAA only) has been proven not to work because resistance soon emerges and repopulates the viral pool. Dual therapy (2 DAAs) works when each DAA can kill the RAVs selected by the other one.

dt

Good question Thurl,

At the moment I suspect the answer is that no one knows because because as far as I know it hasn't been researched let alone trialled. The focus has been on curing not 'maintaining'.

There has been some mention of HIV and the use of retrovirals but what has to be remembered is that in that case there isn't any cure. However, in the case of HCV we now have treatments that cure the vast majority of people first time round. That leaves a few percent who need pretreatment and the majority of those will clear on their second attempt and if you are one of the very, very tiny percentage who don't clear after two tries then there will probably be new drugs to try by then given that getting that far will take you a fair while. So my question would be why would you want to effectively 'warehouse' yourself and wait indefinitely.....and for what?

At the moment I suspect the answer is that no one knows because because as far as I know it hasn't been researched let alone trialled.

The question of sofosbuvir monotherapy has been researched and trialed in the Pharmasset trial ELECTRON. This trial had an arm :
"PSI-7977 400 mg monotherapy for 12 weeks (n=10 GT2/3)"
(sofosbuvir used to be named PSI-7977 before Gilead bought it)
www.prnewswire.com/news-releases/pharmas...tis-c-131441993.html

Here is one report from that trial, coincidentally involving Prof Gane:
www.elpa-info.org/elpa-news---reader/ite...irin-and-gs-5885.htm
"However, sofosbuvir monotherapy or sofosbuvir plus reduced-dose ribavirin for 12 weeks, or sofosbuvir plus standard-dose ribavirin for just 8 weeks, only cured about 60% of treatment-naive genotype 2/3 patients."

Gilead advise that sofosbuvir not be used as a monotherapy and they have trials that back this up. Whether you love Gilead or hate them, the homework was done on sofosbuvir. You really have to go back to the early trials done by Pharmasset to get the full history on how sofosbuvir was tested as a monotherapy and that option was quickly excluded from later trials as being not viable.

dt

Or maybe his first geno test was wrong. I dont think the genotype test is 100 accurate.

FFS. The man had Hep C for 33 years you think all those years of Geno Type tests they got it wrong
and now its right!

I couldn't give one shit if you believe him or his consultant.

You know, I only mentioned him as he was the only person I knew who failed Gilead's Harvoni
the Geno type changing was an interesting part of the story I honestly wish I'd never mentioned it.

Hi dt,

My understanding from Thurl's question was that he was referring to long term maintenance dosing of Sofosbuvir rather that short term curative monotherapy testing as Gilead did with during Electron. I was responding to that when I stated that no research or trials had occurred to my knowledge.

I had already stated my concerns about long term maintenance use of Sofosbuvir due to some potential for resistance development. And that is because Sof is the 'keystone' of many of the most effective HCV therapies at the moment when used with another DAA. Yes there are alternatives but they tend to require 3 or 4 drug combos for less efficacy and more sx.

[qoute]
Oh and in regard to this....

Blimey. Enkel, I know the man in question he was Geno type 4 Pre treatment
and post treatment he was Geno Type 3 his consultant same as mine explained it too me.

Geno type mutation is not unheard of!

I could be wrong, but I think it is unheard of. Mutations of genotype into a more resistant strain of the same genotype, yes. Mutation of one geno into another, I don't think so. My bet would be this person has gotten reinfected with a different genotype.[/quote]

Ah, I deleted my original reply to this;

The person in question was 12 all the way through his Gilead Harvoni he never reached UD
his Geno type was 4 during treatment within six weeks of failing he was now a Geno type 3.
So, no he did not reinfect himself he was never cured in the first place ,the explanation I was given
by him and his consultant ( We share the same Dr) was his Geno type mutated.
You or anyone else may not like the explanation I am simply reporting the facts as explained to me
I only mentioned it as he failed treatment.

I don't want to get into a fight with you, Sir. So if that's what happened, OK. I trust he is the subject of further study as his situation would appear to be unique.

At the same time, as some people here find Tx and waiting for SVR very stressful, nor do I think it is helpful to add to that by having them think their genotype may mutate into another genotype when the literature says it is not possible.

From HCV Advocate , first para of page2:

A blood test is required for the genotype test. Gener- ally, a quasispecies test is only performed for research purposes. HCV genotype testing is only done once since the genotype does not change unless someone is re-infected with a different genotype.

From the CDC about 3/4 of the way down under "Is it necessary to do viral geno typing when managing a person with chronic hepatitis c?":

Once the genotype is identified, it need not be tested again; genotypes do not change during the course of infection.

As far as the accuracy of genotype testing, I haven't been able to find anything. I know PCR tests can produce false positives/negatives and may be repeated and there is a lot of literature about that. But as I couldn't find anything about genotype testing efficacy and as I can't recall reading of a case where they got it wrong, I can only assume there is a high level of accuracy.

Thurl, I'm sorry if you failed to pick up the humour in my comment. I should have added a smiley. I just think that the world is not black and white. There is a lot of gray. There are good reasons for Prof Gane having links to Gilead. It does not automatically follow that he is the devil incarnate. In saying that some of the generics may not be bioequivalent, he is simply stating a fact it seems to me. This does not mean they aren't bioequivalent or, even if they aren't, they won't work. Nor does it follow that he is arguing people should not take them. Indeed, other parts of the interview indicate otherwise.

I have always factored in the possibility of failure and, from the start, determined to keep hammering away from it. After all, with my level of fibrosis what else can I do? But in the meantime, I'm content that I'm giving it my best shot. I'm buoyed by the fact I still had enough get up and go left in me to hunt down the generics. And I'm proud I had the courage to take what I consider to be a well calculated leap of faith but a leap of faith nevertheless.

And I think everybody else is best off focusing on those things too and not the what ifs. If others feel differently, so be it. But personally, beyond having already decided to have another go in the case of relapse, I see no point worrying about crossing bridges that the science says I will probably never need to cross.

dointime wrote:

The question of sofosbuvir monotherapy has been researched and trialed in the Pharmasset trial ELECTRON.

Thank you, dt, for the links to the ELECTRON study. For me it makes rather chilling reading: it appears to establish that Prof Gane could well be right at least as to one thing, namely that sofosbuvir (at least in combination with ribavirin and hence possibly just by itself) is sufficient to suppress the virus while treatment continues and, indeed, to achieve RVR (rapid virologic response) as well. And if he is right about one thing it raises the inference could he also be right about other things? This latter point is perhaps off-topic here but I believe it raises this question: can a chemical like ledipasvir be tested to establish whether or not it is in the appropriate active, crystalline form which Prof Gane speaks of in his broadcast?

Hi all, This whole thread is uneasy reading and to my way of thinking, much of it is speculation.
I am not on Twinvir or Chinese meds, but from what I can see, there have been some pretty good responses to treatment on this medicine.

I cannot really see how this discussion can progress in a way that is positive to anyone until some new evidence either way presents itself?

It is a sensitive time for many on treatment or just ending and I can feel the collective stress levels rise - Mine included !

(edit) It's a shame there isn't more data (as they say) yet to put everyones minds at rest, but until there is, maybe we could have a collective slow breathe in through the nose and out through the mouth !

Chester wrote:

I'm sorry if you failed to pick up the humour in my comment. I should have added a smiley.

Excuse me, Chester, if I had sense of humour bypass. No offence meant or taken by me.

I'm not suggesting Prof Gane has done anything wrong. It is true I am hoping he proves to be wrong in his assertion that there could be defective ledipasvir coming from China or Bangladesh, but that's because that is the type of medicine I am taking. Disagreeing with someone isn't the same thing as accusing them of wrongdoing.

I think we are all worried about relapse. I am perhaps more worried than most because I am taking ledipasvir from Bangladesh and Prof Gane - a noted authority - has said that there could be defective ledipasvir coming from there and China.

Gaj wrote:

So my question would be why would you want to effectively 'warehouse' yourself and wait indefinitely.....and for what?

Well, you may not want to wait indefinitely but at the very least sofosbuvir monotherapy, IF it is sufficient to achieve viral suppression, could provide a stopgap while you researched your options and decided what to do. Yes, cure is better than maintenance therapy but once you have relapsed there may not always be a clear retreatment option available. In the longer term maintaining viral suppression could enable you to wait for the appearance of a new knock-out non sofosbuvir-based pan-genotypic remedy. Or, in my case, it could enable me to wait in a state of viral suppression until the NHS finally agrees to fund my treatment, taking the cost and anxiety of determining treatment out of my hands.