Hep C Discussion Forum

Tig · Admin

RE: Trial for people who failed DAA treatment

mcmaklin · Senior Member

Hi could you Please Clariify why Maviret is worse? What has Abbvie missed. I am thinking about the newest therapy with Pibrentasvir I may be able to receive it maybe. It is probable I had the L31M before treatment - and what is q54h?

BTW I am F1 or F2 not F3

And is there any knowledge saying That Viekira/Exviera I had was not effective against L31M which is probably the only I have now for geno 1b?

"The fact you dont have y93 resistance is good news The other rav at 31 you can kill.

Abbvie missed something, so it only makes sence that you go after the virus with a different bomb."

-- Edited by mcmaklin on Saturday 19th of August 2017 03:45:11 PM

-- Edited by mcmaklin on Saturday 19th of August 2017 03:54:20 PM

Tig · Admin

Allow me to offer some links to RAV information here. We've been discussing this quite a bit and Canuck has added some really interesting stuff that I'll add as well. Give me a few minutes and I'll provide additional links.

mcmaklin · Senior Member

Thank you very much - but why you think Vosevi is the best for me? You just support ot have any data about L31M? Who can help here?

mcmaklin · Senior Member

Hello, I have not been here for a while.

As you maybe know my story is that I have relapsed a month after treatment Viekira+Exviera without Riba. Genotype 1b, now F1. After relapsing I have been found L31M and Q54H (still do not know much about the last one).

Now I am waiting for the newest Abbvie Mavyret or the Vosevi.

I am in UK and in Poland (in Poland I doubt will get the Vosevi).

I need some good data, as probavbly there are no many patients who have L31M.

1. WHICH OF THEM IS BETTER FOR ME? My consultant is thinking of Mavyret. Any data?

2. And do I need to take Riba?

3. Do you know a situation in UK?

thank you

-- Edited by mcmaklin on Saturday 19th of August 2017 07:46:49 AM

mcmaklin · Senior Member

Pablito, yes thank you. But I cannot see any trials for now, unfortunately....

Pablito · Senior Member

Heh Mc

I also saw Prof D privately a few months back. He told me he's working at King's now and is involved in HCV trials so hopefully he'll be able to point you in the right direction.

I got very lucky and sneaked into the Polaris 2 trial just before they finished recruitment.

Pablo

mcmaklin · Senior Member

Hello as far as I know there was a conference now. Do you have any news for me hard to treat?

JimmyK · Guru

41? !!

No worries dear friend, your time is coming. For what it is worth, I was infected as long as you have been breathing and all is now well. wink

The Sun will rise in your future. All things in their perfect time.

JimmyK

Tig · Admin

Hey Mak,

I haven't been able to find much in the UK either. Have you called the Hep C Trust? They are on top of it, at least they seem to be from my side of the pond. There may be new treatments in the pipeline we aren't aware of, so the Prof may have some trial information. Keep us informed.

Hep C Trust

mcmaklin · Senior Member

I am asking because I have a private visit at prof Dusheiko in London soon - I would like to ask for trials in London.

Canuck · Guru

Hi mcmaklin,

Old! sheesh, out of the mouth of babes! hee hee.

Youth is usually always in one's favour when it comes to health issues.

Re: your question - any GS-9857 trials?? - please see this link/thread where a pile of sof/vel and sof/vel/vox (vox=GS-9857) posts have been stashed ( in "General Discussions").

My last look at/for any trials, you will find (about 4 posts down) in the thread I link to you, I have not looked for trials since then.

SOF/VEL and SOF/VEL/VOX

But I would recommend you keep scouring the NCT and keep looking for any current or new trials, but many trials are finished. Also, there are some other threads on this site that speak to obtaining generic drugs, but it would take much sussing on your part to find how one could possibly get generic sof/vel/vox. That might be impossible/improbable at this point. I am not "up" on generics, I recall hearing something about generic vel (out of China?) - don't know.

Have you discussed at length with your doc, what he thinks of sof/vel and sof/vel/vox, in your case, as far as your particular RAV's? Your doc should be "up" on (any) new trials coming out, no? When does he think sof/vel/vox may be rolled out where you are?

Gilead seems to be poised to roll out sof/vel/vox as a "rescue" therapy, for those that have failed other regimes - sof/vel alone has already rolled out in USA quite well, but with riba (for the interim) being used (if required) as the third drug for their "triple". This should change in 2017 (at least in the U.S.A), if and when they roll vox out for use in their sof/vel/vox triple. Gilead did indicate they may roll out this triple in USA first, then Europe (I think). Personally, I would not want to be forced to do riba either, even tho it can be a helpful effective thing.

The U.K. and Canada also seems slow to roll out sof/vel use.

Youth and F1 is in your favour as they keep you waiting.

How are you feeling anyway? Hope you're feeling OK. C.

mcmaklin · Senior Member

Thank you for all your help. I am 41 so not that old.

Do you know about any clinical trials in London for those who failed previous DAA? Or upcoming trials. I cannot find it but where is the phase 3 with GS-9857? I do not want Ribavirin.

Canuck · Guru

Mak,

My 2 cents again.

RAV's or being cirrhotic (in certain failed GT's) who are going for re-treatment, seems to be more problematic in GT 1a's and 3's (less so for 1b's).

You, being a young(?) GT 1b, saying you are F1, with your only RAV's being in NS5A (L31M, and a less significant one, Q54H), then RAV's in NS5B and NS3/4A don't apply to you, and even if they did, those might be less significant for you, as the later are shorter-lived.

Your main concern will be how fit (long-lived) the NS5A RAV's are (perhaps the L31M mostly), so, with your F1 status, perhaps it is not wrong to be delayed somewhat in defining and starting the best treatment, that will best address your RAV's (which you are already doing).

Perhaps restrict your researching to the best NS5A drug regime, that has shown itself to blow past L31M.

Time is a factor with RAV's, so is choosing the right re-treatment drugs and length of treatment, but perhaps another large (or larger factor) is your TT status (versus being CC or CT).

Your doc should be the best source for drug, RAV, TT considerations.

I am way out of my depth here on any of this subject matter, I but offer up my thinking anyway, even if I am dead wrong.

Sorry I can't be of more help.

You never did say how you are feeling ... how is it going? smile

C.

Tig · Admin

Hey Mak,

You mentioned having a decent healthcare team, do you think you could inquire exactly what RAV's they tested for? Knowing exactly what was tested for is important, unless the treatment DAA(s) are highly resistant to all known RAV's (RAS). Until you're confident in your options, keep asking questions. If you haven't been fully tested for RAV's, it is worth seeking.

If I'm covering bases already covered, forgive me. I'm not sure which item you're referring to. If it's about the various NS5A's, the lower the number, the higher resistance the drug has against the RAV. It referred to fold increases. You have to remember, just because a NS5A has low resistance, generally the NS5B will cover it. The options are limited only to access to drugs and care. There's something for everyone out there and they're making it easier to find out.

JimmyK · Guru

mcmaklin wrote:
I have been tested for L31M and q54h which I know I have after relapse - how are they correlated to those numbers like 1, 2, 3.

Greetings,

I am not informed enough to comment on q54h. My sincere apologies for that. But with regard to L31M, Harvoni is quite successful.

JimmyK

mcmaklin · Senior Member

I have been tested for L31M and q54h which I know I have after relapse - how are they correlated to those numbers like 1, 2, 3.

JimmyK · Guru

Greetings friend.

We here are with you and will STAY with you to the Cure.

I am aware of L31M and know that Harvoni is at roughly 80% successful with that particular RAV.

I am not up on the other but will study whatever I can get my eyes on for you.

I do know I was successful with a few more common RAV's and the added problem of Omeprazol with Harvoni x 12 weeks solo.

Do you have potential options wih direct ordering via India? Just wondering so we can help as much as possible.

Hang in there dear friend. We are with you!

JimmyK

mcmaklin · Senior Member

Thank You very much for your care. I have a question.

What are POSITIONS at the article you mention - they are mached with numbers like 1, 6 etc.

I have been tested for L31M and q54h which I know I have after relapse - how are they correlated to those numbers like 1, 2, 3.

Does it mean that there are all RAVs I have been tested or this is what they do - test the most common and other it is some luck? I want to know what happened after the bad treatment.

2. Can you - wiser then me people sort out from this article WHAT of drugs is good for killing L31m and q54h with geno 1b?

Tig · Admin

Hey Mak,

I'm not sure if this was shared previously, but it's worth sharing again. We aren't seeing a lot of new data coming out of the ABT camp. Makes me wonder if the newest Gilead doubles and triples are so effective, interest in the current trial drugs has slowed down a bit, while the competition regroups. That doesn't mean the ABT protocols shouldn't be looked at. Availability and physician preference also plays into the selectiom process. If the regimen your doctor considers covers every base, consider it. We're more than happy to provide our opinion when you have some options.

Here's a link to additional Magellan trial data:

http://www.natap.org/2016/EASL/EASL_13.htm

Canuck · Guru

Hi mcmaklin,

No, I'm not saying that at ALL! (that new abt drugs are "worse") or anything at ALL like that. It is just that I am more familiar with pans like sof/vel/vox and have been hearing about this other new pan NS5A Ravidasvir lately, I just thought you might wish to keep exploring pans period, if you and your doc are not settled on what you think is best for you, or what might or might not be available to you in your country. I thought you had already been exploring ABT drugs with your doc and you were both pretty well leaning that way, so, I just offer up other regimes for you consider with him. That's all. I cannot say which regime is better than another for you, nor which one is best suited to you I am afraid. Sorry I can't be of more help, I wish I was more knowledgeable. Sorry, I don;t mean for you to "read into" my posts about other drug choices "as being a negative" against ABT, I simply laid out drug info choices. I am worried that where you are, drug choices are limited, by both, drug trial and by prescription.

How ARE you doing/feeling? How are your LFT's? I think you said before your Fscore was low? I am guessing you may be feeling frustrated, perhaps to say the least.

On this site, some folk who were on ABT have not responded with feedback for some time, one fellow just finished recently, he did well, but I am guessing the others did well too, but as I say, not many are writing about being on ABT here, I don't think there have been that many here who were on Abt. But I am sure you have already searched around the site and found them and their posts, and the general knowledge/info posts about ABT.

Other than what was already covered by the others (below) in this thread, I don't know what else I could add. confuse

I hope you don't have to be kept waiting too much longer to get a break, and will get access to some good re-treatment drugs soon. smile C.

mcmaklin · Senior Member

Why nobody is writing about newest ABT drugs. Are they worse or what?

Canuck · Guru

Hi mcmaklin,

How are you holding up BTW? This has been a long haul for you. How are things? How are you actually feeling?

Have you read and re-read these threads?

A "new?" NS5A - "PP1-668" (Ravidasvir)

SOF/VEL and SOF/VEL/VOX

Hope you are feeling OK. Let us know how things are going for you. smile C.

mcmaklin · Senior Member

Thank you. If you have more data of treating those who failed DAA and who has L31M and genotype b please let me know. I am still waiting for my options

Tig · Admin

You can bet your last dollar, pound or euro, that the generic labs in India and China are working hard to threaten Gilead with another unenforceable patent right infringement. They did that with Sofosbuvir and won. They're probably ready, that's what they do.* It will then be available like much of the current DAA's are. Mail order is expanding world wide. Be cautious whom you trust if you consider that. It's important to have a local physician that's on board with it. So all of that said, prices will come down for those wanting a generic option. I like knowing our options are improving and getting easier. That's what it's all about!

* jmho

Canuck · Guru

Mcmaklin,

I would still explore (thoroughly) with your doc (or docs) the appropriateness of sof/vel (and/or perhaps sof/vel/vox, when that triplet becomes available), for you in your particular case, considering your prior failure and current RAV's.

I have no idea how the roll-out of sof/vel (Epclusa) is coming along in Poland, nor, when they will start using vox along with sof/vel as a triplet rescue regime for relapsers (anywhere!).

We see, in North America, Epclusa (alone) being rolled out first (with recommendations to add riba if a triplet is warranted). The drug I believe Gilead intended for triplet use with sof/vel was supposed to be vox, and there is not hint about when vox will be available by prescription, except for vague rumours about it coming in 2017.

You should keep searching out (with your doc, and on your own) the likelihood of ALL the drugs that WILL be coming available to you (by trial or on the market), and given that, then which regime is the most appropriate for you.

You cannot count on a perfect trial coming up for you. You should keep scoping ALL your options, and, future options that may come available to you.

You can tell I am partial to sof/vel and sof/vel/vox, and it may become more easily available to more people in the near future by prescription. I think sof/vel/vox should be high on your list to explore

Sorry I cannot help more. I did post some odds and sods over in "Knowledge Base" ... "About ABT-493/450", just some reading material. C.

Tig · Admin

Hey Mak,

Yes, Sovaldi (Sofosbuvir) is classed a NS5B polymerase inhibitor. Here is some data from Gilead.

Sovaldi

mcmaklin · Senior Member

Hello - thank you all for your heart. I have updated my signature.

TIG56:" It makes one wonder if another round of the ABT 493/530 combo, with an NS5B addition would be the ticket."

Is Sofosbuvir NS5B?

Canuck: in your country, if it is Poland, what drugs are available to you, easily, without being in a trial? What drugs does your doc think he can get for you, now, or by way of waiting for a trial there? (BTW - I still have not scoured up another failed 1b, just like you, yet). Is it a possibilty for you to find the drugs you and your doc have decided might be best for you elsewhere if they are not available to you now where you are? Just a leave-no-stone-unturned thought.

It is Poland - maybe there will be just one trial for people like me who did not get cured with Abbvie - I am the special one 1b no cirrhosis. Normally with waiting available Harvoni, Viekira+Exviera and soon Velpatasvir, and all other necessery like Olysio also available - not very easily but yes

-- Edited by mcmaklin on Friday 16th of September 2016 09:26:48 AM

Canuck · Guru

Tig,

Yup I knew you put it there for reference.

I also just highlighted for mcmaklin that even this regime may not be easily available.

Agree on all else you bring up ... and, like you said, it will all depend on what is available to him. C.

Tig · Admin

Hi C,

I listed the trial info strictly because he asked about Vox and they help describe the protocol and goals. It makes one wonder if another round of the ABT 493/530 combo, with an NS5B addition would be the ticket.

I think it depends entirely on what's available or will be in his region of the globe. I don't believe ABT and Gilead have plans to get friendly anytime soon. Used to be the chance to go off label, but I don't hear much of that anymore. Most insurance carriers, some doctors and governments have agreements and deals with Big Pharma$. It's big, big money. This was planned out long ago. Competition and licensing red tape should be visited.

We need to see routine RAV screenings pre treatment, and we're not. Here anyway. Any history of tx failure should be an automatic, regardless of time post failure. My opinion of course. There are so many considerations now, it's important to have a comprehensive list of resistant varients or a protocol unaffected by them. I think we're getting closer with each new discovery.

That's my wink

Canuck · Guru

We are kinda right back where we started.

Pablito - Nor could I find any 530/493 trials, anywhere, that exactly fits the bill of what mcmaklin or his doc have suggested as "best" for him and his particular parameters. Close to the "wanted" regime does not exist (that I could find), and other trials (that focus mostly on 530/493 alone) were recruiting only for liver transplant pts., HIV co-infected, etc.

Tig - The sof/vel/vox trial info you pulled up for reference, as well as all the other sof/vel/vox trials that have been listed - we encounter the same thing, the exclusions exclude mcmaklin as he stands, and/or were not recruiting, and most of the locations were Can, US, Aus, Germ, France, Puerto Rico. Although RC thought VOX may come to "market" in 2017?

Mcmaklin - you did not say your home country (or what country you will/or could be treated in) ... in your country, if it is Poland, what drugs are available to you, easily, without being in a trial? What drugs does your doc think he can get for you, now, or by way of waiting for a trial there? (BTW - I still have not scoured up another failed 1b, just like you, yet). Is it a possibilty for you to find the drugs you and your doc have decided might be best for you elsewhere if they are not available to you now where you are? Just a leave-no-stone-unturned thought. Perhaps many trials have ended and the next best thing coming to market will be the sof/vel/vox triplet as a rescue regime.

Sorry I can't be of more help. C.

Pablito · Senior Member

I'm unable to find mention anywhere of a trial between the ABT drugs and Sovaldi.

- - - - - - - -

True dat. That's the big thing missing from the DAA science. It might be because it's still early days or that it's an oligopoly with a handful of companies making the drugs with a lack of desire to go head-to-head, complicated somewhat by most regimes using sofosbuvir as the backbone with Gilead owning the rights to this....

...but if we did have these head-to-head trials then we could make more astute decisions about which ones to choose.

JimmyK · Guru

Good stuff Tig!

MC we are with you! We will get there!

JimmyK

Tig · Admin

There isn't much information available, but here's a trial reference to the regimen from the US.gov website. I'll add anything I find that might help you gain knowledge.

S/V/V trial

JimmyK · Guru

Tig56 wrote:
Mac,
I'm unable to find mention anywhere of a trial between the ABT drugs and Sovaldi. Who knows what the future might be, but I kind of doubt there will be any formal research done, like a 3 phase trial between the two companies. Gilead is already moving beyond the current treatments, and have just released Epclusa, which is a combination of Sovaldi and Velpatasvir. Voxilaprevir (GS9857) is a NS3 Protease Inhibitor that has been in phase 3 trials for quite awhile now. Gilead will be offering it as a triple regimen. It has been very effective.
Sov/Vel/Vox

Brother I agree and want to make sure our friend in Poland is OK and well informed.

JimmyK

Tig · Admin

Mac,

I'm unable to find mention anywhere of a trial between the ABT drugs and Sovaldi. Who knows what the future might be, but I kind of doubt there will be any formal research done, like a 3 phase trial between the two companies. Gilead is already moving beyond the current treatments, and have just released Epclusa, which is a combination of Sovaldi and Velpatasvir. Voxilaprevir (GS9857) is a NS3 Protease Inhibitor that has been in phase 3 trials for quite awhile now. Gilead will be offering it as a triple regimen. It has been very effective.

Sov/Vel/Vox

JimmyK · Guru

The fact that you are dealing with a combination of competing manufacturers makes me question the validity of such a trial.

We here want to make sure you have all your facts straight so we can properly assist and I assure you, that you are on my mind and in my prayers. I really would like to help you out my friend. :)

JimmyK

-- Edited by JimmyK on Thursday 15th of September 2016 02:44:53 PM

mcmaklin · Senior Member

What is VOx? And do you think Abbvie both with Sofosbuvir is safe? How is it possible to take it in trials of nobody was testing it? I guess it will not be phase 1

Pablito · Senior Member

ABT-530 + ABT-493 + Sofosbuvir and Ribavirin - that's your ticket IMO, but you'll be the first on this forum to be on this combo. I would imagine that it's only the ribavirin that would cause sides (anaemia).

As wedded as I am to sof/vel/vox, having been on this myself, I think Abvie combo is slightly better given your profile, but Eclupsa + Vox is a close second. I'd be looking for 12 weeks rather than 8. I can't see them giving you 24 weeks.

Pablo

Cheddy · Moderator

You always do

Tig · Admin

Never fear, we'll catch you!! biggrin

Cheddy · Moderator

That just makes me dizzy.

Tig · Admin

I'm not familiar with any discussion on a specific trial dealing with that here on the forum. I found some information on the Magellen trials that you can read. The NS5A RAV's are the most persistent, but they believe the newest NS5B and NS3/4a drugs are most effective in defeating them. Whether another round of the ABT protocols, along with the addition of an NS3/4a PI is the answer, I don't know for sure but they are leaning that way.

The addition of a NS5B may be warranted to defeat the RAV's.

Magellan trials

The prevalence of naturally occurring resistance mutations against NS3 protease inhibitors, NS5A replication complex inhibitors, and NS5B polymerase inhibitors in patients with hepatitis C virus genotype 1b

Kazuhiko Hayashi, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Yoshiaki Katano, Yoshiki Hirooka, Hidemi Goto;

Gastroenterology, Nagoya University, Nagoya, Japan

OBJECTIVES: Numerous direct acting antivirals (DAAs) such as NS3 protease inhibitors, NS5A replication complex inhibitors, and NS5B polymerase inhibitors are developing and phase III clinical trials of these DAAs combination therapy have been conducted. DAAs combination therapy is less advert events, better tolerated and high eradication rate of HCV. However, the shortcoming is drug resistance associated amino acid variants (RAV). HCV genome is very short half-life and replicates at rapid turnover with lacks proof reading activity. This mechanism of HCV replication naturally induced RAV to DAAs. It has been suggested that the preexisting RAV might be one reason for treatment failure. There were a few reports about natural occurrence of RAV but their prevalence is not fully understood. The aim of this study was to investigate RAV in NS3, NS5A, and NS5B regions in patients with HCV genotype 1b. METHODS: Two hundred seven patients with chronic hepatitis C genotype 1b were enrolled. All patients were naïve to DAAs. Identification of resistance mutations in the NS3 (position at 36, 54, 80, 155, 156, 168, and 170), NS5A (position at 31, 54, 62, and 93), and NS5B (position at 96, 282, 316, 414, 423, 448, and 495) regions by direct sequencing. RESULTS: NS3 mutations V36L (N=2), T54S (N=6), Q80K (N=1), S138L (N=1), D168E (N=3), V170L (N=1), and V36I+Q80R (N=1) were detected and mutation rate was 7.2%. R155K and A156V which are lead to a high level resistance to NS3 inhibitors were not detected. NS5A mutations L31M (N 8), L31V (N=1),Q54H (N=42), Q54P (N=2), Q54K (N=1), Q54L (N=1), Q54N (N=2), Q54S (N=1), Q54Y (N=3), Q62E (N=2), Q62H (N=1), Q62N (N=1), Q62S (N=4), Y93H (N=7), L31I+Q54H (N=1), L31M+Q54H (N=2), Q54H+Q62E (N=8), Q54H+Q62A (N=3), Q54H+Y93H (N = 10), and L31M+Q54H+Y93H (N = 1) were detected and mutation rate was 48.3%. L31M and Y93H which associated with high level resistance to NS5A inhibitors were frequently found. NS5B mutations C316N (N=54), M414L (N=2), Y448N (N=2), and C316N+Y448N (N=1) were detected and mutation rate was 28.5%. S282T which is RAV for nucleoside NS5B inhibitor was not found. 8 patients simultaneously have RAV in both NS3 and NS5A regions and 12 patients simultaneously have RAV in both NS5A and NS5B regions. CONCLUSIONS: The preexisting RAV for NS5A inhibitors and nonnucleoside NS5B polymerase inhibitors are frequently found but the naturally occurring resistance mutations against 2nd generation of NS3 protease inhibitors and nucleoside NS5B polymerase inhibitors are rare. These results indicated that the combination of 2nd generation of NS3 protease and nucleoside NS5B polymerase inhibitors would be optimal IFN free regimen.

Disclosures:

Hidemi Goto - Grant/Research Support: MSD, Roche, Bayer, Bristol-Myers, Eisai, Ajinomoto, Otsuka, Astra, Tanabe

mcmaklin · Senior Member

I have been told that maybe there will be a trial ABT-530 + abt-493 + Sofosbuvir And Ribavirin.
No data yet. Antybody here taking a simillar combo? How safe is it? Will I be the first one?

mcmaklin · Senior Member

I have translatMed the document From my language. I asked to test for mutation Y93h and L31M this is what they were able to do in region NS5A and my doctor for some In region NS3.

this is the result:

In region NS5A among mutations L31M and Y93H:

mutation L31M confirmed to be present,

Y93H NOT PRESENT in referral sequence AY045702 for genotype 1b

Additinally confirmed to be present Q54H

In region NS3 I have no mutations D168A/F/H/N/Y/V. And not possible to estimate Y56h (too small viral load, or genotype different than 1b

Tig · Admin

Definitely going to need current RAV (RAS) results before you can determine your options. Sovaldi is effective against more variants, so one of the new Epclusa w/wo Vox will be the ticket. What was the name of your trial? You might add that info in your signature, it helps when replying. All information on results are welcome.

There are some good options available and more research on the way. You shouldn't have much of a wait to retreat. Stay involved with your doctors, the news is coming fast these days. We'll do our best to stay on top of it. Keep in touch.

JimmyK · Guru

In 1B subjects the presence of resistance mutations in NS5A (L28V, L31M, Q54H, Y93H and I280V) were observed in 16/30 (53.3%) patients in one study. This is in treatment naive folks so 53.3% had preexisting RAV's as I read it. That is significant.

I am going to offer a study I don't think is here.

http://virologyj.biomedcentral.com/articles/10.1186/1743-422X-10-355

Lots of interesting information and sorry but it is a long read.

Regards

JimmyK

JimmyK · Guru

Greetings.

I am a little concerned with the statement; "I have probably no NS3 RAVs -"

Mainly the term "probably".

Do you have copies you can share on the testing done to determine the RAV existence and drug resistance? Something like the attached.

The reason I ask is because it would be very helpful in determining the predicted resistance to particular DAA's.

Can you post the document that show, NS5A RAVs L31M and Q54h and genotype 1b?

Thanks and hang in there, you will be fine. I failed V-Pack with RBV as a 1A.

JimmyK

Canuck · Guru

Hi,

You said ... I have probably no NS3 RAVs - I have NS5A RAVs ...

I did note that, and that WAS on my mind, as was my pondering about what amount of professional advice you had been given thus far by your doc (or docs). I cannot recall where it lives, but I did read a thing on re-treatment of failures (in your situ) with 530, which did side with what you and your doc have come up with thus far.

Are you looking for confirmation, second opinion, or are you having doubts with what the thinking is thus far that you and your doc have come with?

I am waaay out of my depth here. I'm sorry if I can't think of anything else helpful to add, other than ruling out any benefits the sof/vel or sof/vel/vox rescue regimes may hold over any other re-treatment regime, perhaps what your doc is thinking IS indeed most appropriate for you and your specific conditions - i would not know. I will scour around the site and see if I can find some other person in your same failure position tho, seems to me there was a Viek failure (or two), but perhaps one of them did ledi 2nd time round - I can't rightly recall any of it right now without looking for it. I will look.

I am hoping anybody (maybe another fellow 1b) with more info or good guessing/opinion will enter here. Perhaps someone with more of a grasp of RAVs such as Tig or mallani can help with questions.

If in doubt, what about another professional opinion from another hep doc, on the best re-treatment regimes for 1b's with your RAV's? Can you wrangle a "second opinion" appointment with someone? Sorry I can't be of better help. C.

Pablito · Senior Member

Yes, RAVs can either be present pre-treatment or occur during treatment. They vary in strength (i.e. to what degree they cause resistance to a DAA, 2-fold, 10-fold etc.) and the length of time they remain in our bodies for. NS5B RAVs (i.e. against sofosbuvir) are less common and less of an issue as they expire quickly. The big problem is NS5A RAVs, as NS5As have a low barrier to resistance and can last for as long as a year and, hence, why some doctors like to wait to re-treat.

The answers to most of your questions are in the article so do read it. Canuck is correct in pointing out that it does not cover sof/vel/vox in the article. I hear you that vel might be a problem given your RAVs but vox is not an NS5B. Obviously I am not an expert in the issue, but I have read fairly deeply about re-treatment just in case and what to do if in the nightmare scenario where sof/vel/vox fails, and this is what I would want if I was in your situation...

The new Abvie regime your consultant recommends as first preference and sof/vel/vox as the second choice. I'd be gunning for 24 weeks (if this is possible) and would strongly consider adding in ribavirin.

I hope it works out for you.

Pablo

Hep C Discussion Forum

The prevalence of naturally occurring resistance mutations against NS3 protease inhibitors, NS5A replication complex inhibitors, and NS5B polymerase inhibitors in patients with hepatitis C virus genotype 1b

Kazuhiko Hayashi, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Yoshiaki Katano, Yoshiki Hirooka, Hidemi Goto;

Gastroenterology, Nagoya University, Nagoya, Japan

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