Hep C Discussion Forum

5-1-18 · Guru

RE: ALL ABOARD THE VOSEVI TRAIN

robertsamx · Guru

Mac, Nice to see you report in at -ZERO- One heck of a trip to get there! After your failed trial and treatment I understand your apprehension with your current T/X on Vosevi. So whats the plan going forward? Has your main Dr approved the additional 4 weeks of Vosevi?

RC

polosilver · Senior Member

Mak --- Welcome to CLUB ZERO w/UND status!!!! Awesome. Its a beautiful and wonderful experience to slay the ole' dragon, take a deep breath and smile. Well done!!

ps

Canuck · Guru

Hi Mak,

I had to go out of town, but I am back now, and I see that while i was away, you got your long-awaited UND! biggrin

Very good.

That should make you feel a tiny bit better.

After this weekend, (this coming Tues) you said you are having an appointment at your regular hep treatment place?? - with your "official" nurse you said?? - do you not get to have a chat with your hep doc at that same appointment??

I would make sure you request some time on Tues (in addition to seeing your nurse) to also have discussion time with your hep doc, about all your VL results thus far, and your worries and thoughts about extending treatment and your choices. Let him know all the extension options that are available to you (what drugs you might be able to get) and what he thinks of this idea (of adding 4 weeks of epclusa or adding 4 weeks of vosevi to your 12 weeks of vosevi) - please let your hep doc advise you on this by discussing all of this thoroughly with him.

Nice your Mom knows how you are doing. smile C.

-- Edited by Canuck on Saturday 10th of November 2018 02:26:58 AM

Cheddy · Moderator

Great news!!!!

But, Mac, when are you going to get off this notions of self medicating??? You are undetected and still fighting!

As I understand it, we continue treatment to catch any replications in the works or may be hiding.

The dead guys are dead. They just dissolve and follow the natural path of clearing any waste the body doesn't want.

Celebrate! Stand up and dance! It will make you feel better.

And please, follow your doctor's advice. There is no reason to keep treating something that isn't there. When you get 12 weeks after treatment, your doctor will know to do next. I suspect it will be a happy dance.

Hang in there, Mac. You are getting it done.

Hoodietree · Senior Member

Oh my goodness, that is AWESOME!!

UNDETECTED hallelujah thank god!

mcmaklin · Senior Member

Yes I feel much better. Anyway I am thinking about making my treatment longer. My official results will be from last Monday soon, I am wondering what was a day earlier, when was the exact time it went out. I was indeed so stressed. Thank you SO MUCH for your support.

So what we are suppressing now? Can the virus be in body tissues? And I am wondering, if it is in dead hepatocytes HOW does my body remove dead hepatocytes? I am trying to understand what are drugs doing later.

I was very excited, when I told my mum I had problems with speaking. But then I went to the laboratory to confirm because there were no official document yet, they double check it and sign.

-- Edited by mcmaklin on Friday 9th of November 2018 11:48:12 AM

-- Edited by mcmaklin on Friday 9th of November 2018 11:52:44 AM

Tig · Admin

Woohoo! Congratulations Mak! I kind of thought you’d be a bit more excited with this great news. Are you in shock or what? I knew this day would come and here it is. You should be relieved and thrilled! It’s a great thing, enjoy your continued progress. You got this, Brother!

mcmaklin · Senior Member

I have news from last Tuesday. Undetected.

Tig · Admin

Hi Mak,

First of all, your lab work is excellent and yes, dropping enzymes are a clear signal that great things are happening! Stay confident and good things will happen

It is always nice to have our viral load drop to an undetected level early in treatment, but that doesn’t happen for everyone. I mentioned in an earlier post, a friend of mine was still detected at the end of treatment. Her doctor refused to repeat the viral load until week 12. She was about sick with worry, but her doctor was convinced that due to her ever improving enzymes and other blood work, she would be SVR and she was. I hated to see her worry and didn’t like the stress it caused her, but this stuff works, it all works and so will yours. Discuss your concerns here and with your doctor. I know this will work out for you!

mcmaklin · Senior Member

I believe it will come - I do not know if it is predictor but my liver profile is the best ever. Does Alt and GTP falling down say anything? <12 would not do any injure to the liver anyway so it may not mean anything? My main thing that I need to know is if I should be UND while on treatment.

I would like to add that a few years ago in Trials i Was THE ONLY ONE who did not get cured. It was M14-423 Trials.

-- Edited by mcmaklin on Thursday 8th of November 2018 01:10:17 PM

mcmaklin · Senior Member

Thank you. I am trying to think positive, tomorrow I will have results from last Tuesday and on Tuesday i have a visit at my official Nurse.

Tig / I guess I indeed need to be UND on treatment?

Tig · Admin

Hey Mak,

I understand the anxiety of treatment and waiting for that first undetected. It just eats at your stomach and gave me more than one sleepless night. You need to do your best to rid your mind of those fears and concentrate on being positive. Trust me, it feels much better to enjoy a positive mindset than it is to spend your waking hours convinced you’re going to fail. The odds of you failing are minuscule. You’re on the best drug on the market right now and your lab work is as good as it has ever been. Your viral load is too low to count, and the few stragglers that keep you from testing undetected are being mopped up as we speak. Chances are you are completely undetected by now.

The addition of Ribavirin to Vosevi, or any of these new drugs, isn’t common. The studies have shown it serves little purpose, except make you sick. They add it in rare cases, such as transplant patients, but even then, it’s not used often.

mcmaklin · Senior Member

Thank you - I am still so worried. But I do not understand, is it better to try to do every effort to be UND while on treatment, like for eample asking for adding Riba and it gives bigger chances to get cured then not doing anything despite <12?

Tig · Admin

Everything related to your blood work is headed in the right direction, down. They are a clear indication of continued improvements. Be sure you discuss your thoughts on adding Epclusa to the end of your Vosevi treatment.

Obtaining an undetected result is always desirable, but not always the case with these newest DAA’s. Back in the Interferon days, if you didn’t achieve an undetected result during treatment, they would consider stopping it. That’s not the case with the new drugs. They work differently and that’s why some doctors refuse to do a viral load until EOT+12. Hold out for your results and wait to see what your doctor’s recommendations are.

mcmaklin · Senior Member

Hello, I have my updates from end of week 8:

GGT31, ALT15.6, AST22.4, Bili 16.6

ALT and GGT is probably the lowest I ever had. I am waiting for mor results of the VL.

I am patiently waitng for now.

Replying you Canuck it was a week ago the same as before - the same language: found presence of target RNA.

My only question for now, but as I am saiyng I am waiting and not undertaking any decision, as all is prepared to take it in the last moment, even if I have to buy myself.

I understand some people do not have UND at the EOT but <12. I will anynway ask my doctor, but it is not the time yet. I will have my results faster than they officially do.

1. Can making treatment longer with Vosevi, or when I get UND one month more with Epclusa (I know it is downgrading) cause anything good? My way of thinking is that if it is UND it is better to supress it some more, or if it is still <12 it is also better chance to get UND while on treatment than stop the treatment after month 3

2. It is always better to be UND while on treatment?

3. I have ordered Epclusa from India if I ever need it - but if I don't I can give it to someone who needs.

4. I can also buy one box of Vosevi myself if it is absolutely neceserry, It is hard but I can do it if it can give any benefit.

thank you for this

Canuck · Guru

Mak,

Just wanted to clear up a couple things - you referred to something we were discussing prior, you re-phrased/re-interpreted a topic I was bringing to your attention, you said ... "a person that started with Vosevi and Ribavirin at the beginning and than had different drugs. This way you showed me, as far as I understood, some unwise ways of treatment that should not be prescribed. You were surprised by unnecessary movements" ...

I just want to clarify that I have no idea whether their decisions were right or wrong, only docs can/should decide these things - there may have been reasons that none of us are aware of that could explain what happened there. RAV's, or other reasonings/knowledge we will never be party to. None of us can assume what is right or wrong, correct or ill-advised - only your docs can help you make treatment decisions. As I said before, the decisions have to be knowledge based. I did NOT say what they did was unwise, nor did I say it should NOT have been prescribed, I WAS surprised by the story though. I am not a doc, nor very well-read, I only pass along what I think, uneducated opinions or guessings. You simply must be in good council with your docs to get accurate info.

You seem to have 2 doctors advising you - you do not convey what your "new current" doc (the who is treating you with the Vosevi) says about extending your treatment with Vosevi or Epclusa, nor how he thinks you are doing, period, whether he has any concern about you being less than 12 detected, versus undetected, but, you do mention your "old doc" who you think is saying to you that it might be OK to extend your treatment after Vosevi for 12 weeks with Epclusa for 4 weeks.

I did NOT say you should not take Epclusa if you were considering taking epclusa to extend your treatment, I would not do that, I am not a doc, nor at all knowledgeable enough to advise you - that is good that you have at least your old doc making offers of advice to you (if your current doc is not sharing his opinions with you) - it IS the advice of your docs you have to listen to. Switching from one treatment drug to another lesser drug just seems not ideal to me, that is simply just my thinking/opinion, not advice. You indicated ... "my second doc thinks that Epclusa would be enough but Vosevi is 3 drugs and it is always better. You discouraged me of doing this ...", I would NOT discourage you from doing anything your 2 docs have suggested would be OK for you.

You said ... "the test detects for example dead viruses not able to multiply?...", you have hit on a topic discussed by other people before, about why we see people who are detected at less than 12 at EOT but then go on to be SVR12 and 24. The theory (loosely) is that EOT positive people are showing crippled/critically damaged remnants of virus which can never again replicate, I lack a better way to describe this, but that is some of the talk i have read.

So, how much would a "pay for it yourself" box of Vosevi or epclusa cost you?? Are you really in any position to obtain either of these anyway? Are you actually able to get either of these drugs on your own (logistically, financially and or time-wise)?? - ie what country would the epclusa or vosevi have be be travelling from and how long would it take to get here, no point torturing yourself and hashing over all these "what-if's" if extending treatment is not even a feasible or realistic on-the-table option. Most important and firstly is that you need your docs firm opinion on how he thinks you are doing with your less than 12 detected status.

Can you (again) write here (word for word) what it says on your copy of the last PCR results - (the most recent test result you indicated was Mon Oct 29, week 7 or end of week 7) - I want to confirm the lab is still using the same language as in the prior test ... "found presence of target RNA" ...

What day/date is your next blood draw, what day/date is your next appointment with your doc? Later, C.

mcmaklin · Senior Member

Cannuck,

I appreciate your help a lot and thank you that you are not leaving me alone with all my thoughts.

You have a lot of knowledge because you are simply interested in the subject and read as much as possible.

I was surprised when you wrote me about the case of a person that started with Vosevi and Ribavirin at the beginning and than had different drugs. This way you showed me, as far as I understood, some unwise ways of treatment that should not be prescribed. You were surprised by unnecessary movements.

I still believe I will be UND. I do not want rely on you as on my doctor, I want to assure you about this but you have so big valuable knowledge.

When I took my last test <12 I started to be a bit more peaceful, because it obviously shows that virus is possibly going down to UND and this is not going up (because 3 tests week by week prove this) If it happens for more than 3 weeks I think it just happens. I will wait 2 weeks and then see- and than think maybe about buying a box of Vosevi myself - I will have a prescription but the thing is just waiting. It is a lot of money but when there is a small obvious thing that it can help more I will do this. Although my second doc thinks that Epclusa would be enough but Vosevi is 3 drugs and it is always better. You discouraged me of doing this and you may be right.

I am only thinking - is not it like that the test detects for example dead viruses not able to multiply?

I am also curious how many people on this forum with genotype 1b or a and Epclusa or Vosevi where still detected 12 in week 7.

I know it means nothing but I just wonder if 0 while on treatment is a better prediction or maybe adding Riba can cause the 0 while on treatment and. This I do not understand. Or adding the Riba to Vosevi in week 10 for example makes sense or just pain.. No one knows what will happen with <12 when I stop taking pills. I know even taking more Vosevi will not reassure me but a basic question: maybe it is better to do everything so UND is while on treatment. I believe taking meds does not cause that it is >12 detected but not UND. Does it? This is so hard to understand

-- Edited by mcmaklin on Saturday 3rd of November 2018 05:39:58 AM

Canuck · Guru

Mak,

I agree with what Tig said below ... "Just keep taking the Vosevi, its one of the absolute best. If they want to extend it 4 weeks, do it. If not, stay positive and believe what youre doing is right. Youre going to succeed, I feel it!" ...

Your VL has crashed, your ALT has crashed - that is documenting Vosevi's success in you - but you just simply have to have your docs expertise on this matter, just like I said before, you have to discuss all this with your doc and know what HIS belief and opinion is, on how you are doing on the Vosevi.

How would you ever get an additional 4 weeks of Vosevi anyway, and, what would it cost you?

I can only second guess your doc, this is why i stress how important it is for you to be communicating with him, to find out what HE thinks - not once have you relayed how HE thinks you are doing, and I cannot possibly guess, but I suspect he might say he cannot/ willnot make 4 additional weeks of Vosevi available to you, and, that he and the experts would say longer treatment is not necessary. Nothing is going to reassure you, even doing an additional 4 weeks of Vosevi (if you could even obtain it by yourself) will not reassure you. I am guessing (maybe) 6 months or one year, maybe even up to about 2 years after you are cured, will you still have moments of worry, and it will probably take you a long time to finally accept your cure - that what a bad scare/experience can do to a person, it can badly undermine their confidence and belief, but, go ahead, if you think you can get 4 weeks of additional Vosevi, then do it with your docs permission and knowledge of what you are doing. I don't think you will be able to find/get your own Vosevi and if it could be had the price would be prohibitive.

I would be more worried had your VL ever increased, but it has not, it has crashed and stayed there. I would question the success if the VL was increased and/or if the ALT increased (as outlined in the guidelines), but your ALT has not increased. (So far you have displayed this very good response to Vosevi, crashed VL's and ALT's, and they have stayed there - you have so far continued to sustain this very good response.

Believe in one thing Mak, we are all on your side! - your doc, and Gilead, and all of us! C.

mcmaklin · Senior Member

One thing- as far as I read here it is always better in such situation to continue one more month with Vosevi.

Do you mean that at some moment it should be <12 undetected? Better while on treatment but possible after the end of treatmen?

Tig · Admin

You have a stubborn Dragon, Mak! I will continue to believe, with your viral load below quantitfication, the mop up process is underway. I have a friend that was detected at the end of 12 weeks of treatment (different DAA drug) and was SVR12. These drugs work differently in each of us. She was convinced it would come back, but has been over two years clear of the virus now. Just keep taking the Vosevi, it’s one of the absolute best. If they want to extend it 4 weeks, do it. If not, stay positive and believe what you’re doing is right. You’re going to succeed, I feel it!

mcmaklin · Senior Member

Tig - it says DETECTED.

Tig · Admin

Does it say detected anywhere on the report? Your lab may not provide that. The VL <12 indicates your viral load is below the lowest level of quantification. 5 years ago the lowest they could go, was 100. If it doesn’t specifically say it is still detected, you need to make a call and find out. The Bilirubin is only slightly elevated and the rest are within normal limits. I think they are quite good.

They never list your viral load as zero, ever. It will be <12 iu/ml (lloq) and say undetected. They don’t use the term Zero with this test.

mcmaklin · Senior Member

Hello - Monday 29th which is the end of week 7 still detected <12

7week GGT34, ALT 19.1 AST 26.4, Bili 17,9 , VL<12

I will have my official tests on Monday, results will be maybe a week later or more then 2 weeks to EOT.

I may have a possibility to consult a doctor but have to be prepared to prolongate with Vosevi. I do not think it is possible to receive this officially from the hospital.

About this what you wrote before - does making treatment longer creates a chance to have 0 while on treatment ?

Canuck · Guru

Mak,

Instead of concentrating all your energies and thoughts to these nuances in the studies, details about being detected (at less than 12 or 15) versus being undetected, I would far rather see you having in-depth discussions with your doc about how HE thinks you are doing on the Vosevi, what HE thinks about the importance of still having a a "quantifiable positive" (less than 12 or less than 15) PCR at EOT, versus being undetected, and whether HE would agree with you that you need more drugs, OR whether HE considers a <12 or <15 at EOT+12 weeks to constitute SVR12 and a cure.

Based on the reason of being less than 12 versus being UND, you say you are considering taking Epclusa (perhaps for 4 weeks?) - immediately following the Vosevi - (Epclusa which you would obtain on your own) in order to continue treatment longer than the 12 weeks of Vosevi - ask your doc if he agrees with this. Extending therapy with differing drugs is an important decision. Extending treatment, which drugs and for how long, has to be a knowledge-based decision.

Ask him (if anyone for any reason thought it necessary to continue therapy beyond 12 weeks of Vosevi) whether he can/would be able to get more Vosevi for you - I think not, I think you will have difficulty obtaining "extra" Vosevi period, and that he will likely say extra Vosevi is not required, and that extra treatment (beyond the 12 weeks of Vosevi) is not required. But, I am only second guessing your doc.

You have to clarify these things with him. C.

mcmaklin · Senior Member

So it is no better to be UND then to be <12 at the end of treatment? I will study more of it. English is not my main language and it was not so easy with these texts. I must have mixed somthing.

By the way I just got to know that in my previous treatment on trials I was startting with just the same 1,4mln and 4weeks i was 72 and they have no other data apart from that I was UND at the EOT.

Saying this: 62% of them were GT1's - (9% of these GT1's) ended up being positive at EOT but got SVR12 ...

you mean that all of those who were positive at EOT (I assume it was below level of Quantitive) that they were all cured?

It seems for me I am reding it correctly: 100% of EOT+ patients went on to reach SVR12

This was confusing to me: trials demonstrated that 55% of EOT+ patients went on to achieve a sustained viral response (SVR) 12.¹ So I was thinking they were not all of +patients at the EOT who obtained SVR. I am still a bit confused if it is 55% or 62% or what.

I am impressed by your knowledge and please forgive me as I am in stress too often now

-- Edited by mcmaklin on Wednesday 31st of October 2018 04:22:14 PM

-- Edited by mcmaklin on Wednesday 31st of October 2018 04:24:27 PM

-- Edited by mcmaklin on Wednesday 31st of October 2018 04:26:47 PM

-- Edited by mcmaklin on Wednesday 31st of October 2018 04:28:55 PM

-- Edited by mcmaklin on Wednesday 31st of October 2018 04:29:27 PM

Canuck · Guru

mcmaklin wrote:
I read al of this. Thank you!
- Two things are unclear for me: Does it all mean that when a patient is <12 at the end of treatment he has no more chances for relapse than when he finishes with 0?
- And from your previous post - I do not understand how many patitents with a genotype 1 where <12 at EOT and how many of them relapsed
_____________________________________________________________________________________________
So, if you read the whole of my posts (this one I bump up here again - I copy it here from below - from 3 days ago) .... if you read the details, such as the references to the studies, marked as (1) and (2), you can read those study details for yourself .... ie. the studies were comprised of about 89 people toal, 62% of them were GT1's - (9% of these GT1's) ended up being positive at EOT but got SVR12 ...
(Excerpt only) - for full info see Journal case study
Gastroenterology
Written by Miguel Malespin MD
The presence of end-of-treatment viremia (EOT+) in patients treated with direct antiviral agents (DAA) can be stress-provoking to patients and providers alike. This case series further prompts the question of whether EOT+ is, in fact, a predictor of treatment failure with DAAs. Prior data obtained from 12 interferon-free clinical trials demonstrated that 55% of EOT+ patients went on to achieve a sustained viral response (SVR) 12.¹
Our group further evaluated EOT+/SVR12 in clinical practice and showed this phenomenon to occur in only 6% of HCV mono-infected patients treated with DAAs.² Furthermore, 100% of EOT+ patients went on to reach SVR12, with EOT+/SVR12 occurring in only genotype 1a/b patients with advanced fibrosis/cirrhosis and by Abbott RealTime PCR assay (ART; Abbott Laboratories, Abbott Park, IL).² Although there remains no consensus on why EOT+/SVR12 occurs, we can definitely conclude that EOT+ is not associated with treatment failure in patients treated with DAAs.
References
1. Harrington P, Deming D, Komatsu T, Naeger L. Hepatitis C virus RNA levels during interferon-free combination direct-acting antiviral treatment in registrational trials. Clin Infect Dis. 2015;61(4):666-667. https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/civ402
2. Malespin M, Benyashvili T, Uprichard SL, et al. Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies. Therap Adv Gastroenterol. 2017;10(1):68-73. http://journals.sagepub.com/doi/10.1177/1756283X16672392

Tig · Admin

The PCR test will never state 0 (zero). It always lists the test result as less than the LLOQ (Lowest level of quantification) and typically will state clearly, Detected or Undetected. They are only able to quantify (count) to the lowest level the equipment is capable of and that is 12-15 IU/ml. The sensitivity is another thing and that’s where the detected/undetected result falls into place.

mcmaklin · Senior Member

I read al of this. Thank you!

- Two things are unclear for me: Does it all mean that when a patient is <12 at the end of treatment he has no more chances for relapse than when he finishes with 0?

- And from your previous post - I do not understand how many patitents with a genotype 1 where <12 at EOT and how many of them relapsed

Canuck · Guru

I just want to bump this up here again to try to define SVR ...

Basic premises (and semantics) that need to be understood, about ... what constitutes SVR12 ... and it is NOT whether you are "UND", it is if your PCR shows that you are "below the lower limit of quantification" (below LLOQ) which for most of us, and the labs we go to, the LLOQ is often either <12 or <15 ...

Phase 3 Harvoni trials used this language ... Sustained virologic response (SVR) was the primary endpoint and was defined as HCV RNA less than LLOQ at 12 weeks after the cessation of treatment. Relapse was a secondary endpoint, which was defined as HCV RNA greater than or equal to LLOQ with 2 consecutive values or last available post-treatment measurement during the posttreatment period after achieving HCV RNA less than LLOQ at end of treatment."

So, who agrees with, or does not agree with, this above definition of SVR as used/written by Gilead?? And as similarly written by other docs and guideline regulators?? - (see also below). Maybe I am mis-interpreting how this should be read as far as defining SVR??

____________________________________________________________________________________________________________

AASLD/IDSA Guidelines as readily noted for USA, and as similar to EASL/EU guidelines, these should be quite similarly found guidance for UK.

Excerpts below are from the current Guidelines:

Section - "Monitoring Patients Who Are Starting HCV Treatment, Are on Treatment, or Have Completed Therapy"

Recommendations for Discontinuation of Treatment Because of Lack of Efficacy
RECOMMENDED	RATING
If HCV RNA is detectable at week 4 of treatment, repeat quantitative HCV RNA viral load testing is recommended after 2 additional weeks of treatment (treatment week 6). If quantitative HCV viral load has increased by >10-fold (>1 log₁₀ IU/mL) on repeat testing at week 6 (or thereafter), discontinuation of HCV treatment is recommended.	III, C
The significance of a positive HCV-RNA test result at week 4 that remains positive but lower at week 6 is unknown. No recommendation to stop therapy or extend therapy can be provided at this time.	III, C

Further, in the guidelines ... "it is essential to test for HCV RNA 12 weeks (or longer) after treatment completion. Undetectable OR unquantifiable HCV RNA 12 weeks or longer after treatment completion is defined as a sustained virologic response (SVR), which is consistent with cure of hepatitis C infection" ...

_______________________________________________________________________________________________________

With no other influencing factors such as certain ALT performances, based only on having a non-elevating (a maintained) and/or decreasing unquantifiable VL during treatment (less than the LLOQ) and/or that it remains to be thus (a suppressed unquantifiable VL at EOT+12 weeks), THIS then would be considered SVR at EOT+12.

I believe you are correct Mak, your current UK doc (based on guidelines) probably would not be considering you to be failing, just based on your obvious response to the Vosevi, there is no guideline supporting him to treat you differently than giving you the 12 weeks of Vosevi. If he did it would be of his own prerogative, and it could prove not straight forward for him to do so.

I would have no argument with your "other old" doc, about there potentially being "no real harm" in treating you longer, I am sure you would find it reassuring to get an extra 4 weeks of Vosevi, but longer treatment according to your response thus far, and according to what the experts recommend, may be just a waste of treatment time and money if it is not actually required/when it is not necessary, and if it would be "redundant" (according to the guidelines) - there is NO provision for lengthening a course of Vosevi from 12 weeks that I have ever read, other than a doc doing so by his prerogative and of his own volition, and presenting his arguments for extension to the bodies in control of doling out the drugs (NHS or whatever body your and doc and your country happen to be dealing with).

Your doc has no UK guideline (given your good response to the Vosevi) to extend your Vosevi longer than 12 weeks. But he is the one you should be talking with about all this anyway - does he feel you would benefit from 4 more weeks of Vosevi? At best and perhaps more easily he might offer you additionally riba to what is left of your 12 weeks of Vosevi - which has not really shown in trial data to boost the outcome of a 12 week Vosevi treatment by much, if at all.

If I was a prior relapser, and if I was on a course of Vosevi as my second treatment - it certainly would not be my first choice (nor would I wish to switch) to finish up my treatment with additional weeks of a lesser combo such as Epclusa only because it would mean a discontinuation of the VOX. Once on Vosevi I would finish with Vosevi, period, no matter if it was just for this normal 12 week course, or in the unlikely event you were to be given a 16 week course of Vosevi. As an extention, Epclusa with riba is NOT a substitution for the Vosevi and it's VOX.

Now, having just said that (that I would stick with the same triple, Vosevi, IF the course had to be extended), here is another oddity I found, just to confound the wisdom of that theory of not jumping drug ships - who knows what the exact reasoning was for this 4 week extension (below) whether it had to do with very specific RAV's (perhaps?, but I don't guess so), or, perhaps just lack of access to getting Vosevi for another 4 weeks (maybe more likely), that elicited this further extended and modified regime ... where after 12 weeks of Vosevi+riba, and additional 4 weeks of completely different drugs are provided (different drugs, save for the SOF/RIBA)! Weird (at face value) without an explanation! Another unexplained curiosity is why she even had the riba added to Vosevi from day one in the first place. This patient (early in 2018) seemed to have received her initial 12 weeks of Vosevi/riba via a Canadian doc, and then added (a further) 4 weeks of another treatment via an Australian doc! What makes it odder still is that she had been showing a good response via her ALT performances and being <15 at week 4 and UND at week 8. shrugs

https://fixhepc.com/support-forum/gt1/1817-re-treating-with-vosevi.html

In an old post to you Mak, I showed you a fixhepccom thread that outlined their "Redemption Trials" which included Epclusa but not Vosevi. Like all countries keenly interested in Vosevi coming to market, Vosevi hit the USA first, and was slow to get past the post everywhere else. Vosevi, although spoken of fairly intensely in Aus and in many countries other than USA since 2017, it continued to be nuanced in UK, Canada and Aus in 2018 as far as costs/deals/use, etc. Vosevi has been accepted and listed on Aus books (NPS and TGA) but I would also like to know HOW MANY people have actually been offered and treated with Vosevi in Australia!

5-1-18 · Guru

mcmak,

have you tried begging your doctor for the extra time?

what was your previous treatment? was it with the same doctor?

mcmaklin · Senior Member

I know maybe for people in America it is more difficult to understand it but in Europe you can have what they offer in treatment regimes, it is not that it is "my insurance".

lamassu · Senior Member

robertsamx wrote:
Mac, I believe its 8 weeks supression after you go und. No matter what you end up doing MAKE SURE its with your Drs blessings. Last time i checked with Jeff in Australia the vosevi was not available in generic form. RC

Yes there is no generic Vosevi manufactured in countries like India where generic Epclusa is licensed and manufactured. What I find interesting is that Gilead does not appear to have any new HCV DAAs in the pipeline. That would probably mean they will not license a generic Vosevi for some time.

robertsamx · Guru

Mac, When my Dr ordered the extra 4 weeks of vosevi, my insurance turned it down saying it was off lable. I appealed it and won. Try to get the extra 4 weeks vosevi. RC

mcmaklin · Senior Member

epclusa only is available

robertsamx · Guru

Mac, I believe its 8 weeks supression after you go und. No matter what you end up doing MAKE SURE its with your Drs blessings. Last time i checked with Jeff in Australia the vosevi was not available in generic form. RC

mcmaklin · Senior Member

One thing here. I do not think NHS will prolongate my treatment.

I will have to Buy one bottle of the Vosevi mySelf (very expensive but possible) or to order Epclusa from India. Epclusa is Vosevi Without Voxilalrevir. Does it make sense not to add Voxilaprevir or it is absolutely necessary? I have the officcial Doctor (so they want to test me at week 8) and also another one i was on triala before. The second one says it is not a bad thing to make the treatment longer.

RobertSamx- I remembered this what you said before- that it is important to suppress the virus for at least 4 weeks when it is a zero. This is why I started to worry - but it it wise to think of it.

-- Edited by mcmaklin on Monday 29th of October 2018 08:19:47 PM

robertsamx · Guru

HI ALL. I wanted to chime in on mcmak and his progress. Mac , I understand what it is like to have failed a couple treatments, so its no wonder your so worried about how yours is coming along. In my case i had failed 2 treatments so VOSEVI was about the only choice we had. it had just been FDA approved two weeks before my transplant. Originally my R/X was 12 weeks Vosevi but by week 8 i was still detectable. My Dr called at week 8 and said he wanted to add ribavirin and also add 4 more weeks Vosevi extending my treatment to 16 weeks Vosevi . So that I am clear, my treatment came out to be as follows

16 weeks VOSEVI, with riba added for the last 8 weeks. I took riba the last half of my 16 week treatment.

It was very important that i was on treatment for at least 8 weeks undetectable,that 8 weeks und on treatment gave the R/X drugs time to mop things up . The addition of riba was our insurance that gave the VOSEVI the extra boost i needed. I dont think the riba helped and i think the 16 weeks of Vosevi would have been all i needed but as you know after two failed treatments, you start grabbing anything to help.

Mac- In your case I dont think its a bad idea to get the extra 4 weeks of vosevi and extend your treatment to 16 weeks. RC

5-1-18 · Guru

i too thot mcmak was stopping tx and then getting other pills ; but then realized it was actually pills for a longer tx after eot in dec.

but with so many weeks to go you are doing a good job mcmak. keep up the good work.

we are cheering you on

5

Hoodietree · Senior Member

This is one of those cases where I am glad I misunderstood!

Are you afraid that your insurance won't cover the prolonged course of treatment?

What does your doc have to say about it?

mcmaklin · Senior Member

You misunderstood me- I wrote it not clear enough I am sorry. I will take all I need the Vosevi Till the end. I will not be taking more after I finish - I was thinking of adding other drugs after I finiish like an extra month

Hoodietree · Senior Member

don't stop taking your pills

don't stop believing

don't stop taking your pills

-- Edited by Hoodietree on Sunday 28th of October 2018 03:27:37 PM

5-1-18 · Guru

mcmak, you have lots of weeks left for the vosevi to do it's job but i understand the idea of wanting to make sure. the doctors do know what they are doing now days.

your job is to follow this to the letter and find some ways to relax.

[2nd Vosevi12wks- SOT Sept 12,2018 to EOTDec ]

-- Edited by 5-1-18 on Sunday 28th of October 2018 08:17:00 AM

mcmaklin · Senior Member

No, no. For now I am not going to be on treatment any longer.

I am only concidering, depending on what will happen. I will order Epclusa from India just in case. But I will not be taking any decision myself.

-- Edited by mcmaklin on Sunday 28th of October 2018 07:28:30 AM

5-1-18 · Guru

mcmak, yep it's a scary deal to wonder if this time it will work.

i didn't do the full interferon tx's cos i was an early nonresponder so was spared. but i was still worried at test time becos of that one negative experience. but with these daa's they don't take us off cos they are created to cure what ails us.

what did you take before?

hang in there. we are all here cheering you on and thinking good thots towards your liver and your wellbeing.

how much longer will you be on tx? i forgot blankstare

5

-- Edited by 5-1-18 on Sunday 28th of October 2018 07:26:21 AM

mcmaklin · Senior Member

thank you. I want to assure you that I am reading all posts carefully. I also was trying to find those people on the forum, that you mentioned. I had a problem of finding a person who was not und In week 6 and for genotype 1b.

Your knowledge is incredible. I assume it would be better to already have UND than <12 but this does not mean too much. I am ONLY considering - but I will see how it is going- to ask my doctor to make treatment longer with the Epclusa if things go too slow. And only because I would have to order it from India I need to prepare earlier but I am trying to thing a good way and I have a lot of Hope.

Canuck · Guru

Just more studies for you Mak,

Published in Gastroenterology

Journal Scan / Case Study · October 11, 2017

Clinical Cure of Hepatitis C Virus Is Possible Even With Detectable Viremia After Treatment Completion

TAKE-HOME MESSAGE

· This small case series reported that 5 patients with a detectable hepatitis C virus level after completing treatment with direct-acting antivirals, 1 with detectable viral levels 4 weeks after completion of therapy, went on to have a sustained virologic response.

· This case series highlights two important concepts for practitioners treating hepatitis C virus. The first is that a detectable virus level at the end of therapy does not mean that a patient will not achieve a sustained virologic response. The second is that clearance of the virus may take up to a month or longer in those patients with a detectable virus level at the end of therapy.

Eric Kallwitz, MD

(Excerpt only) - for full info see Journal case study

Gastroenterology

Written by Miguel Malespin MD

The presence of end-of-treatment viremia (EOT+) in patients treated with direct antiviral agents (DAA) can be stress-provoking to patients and providers alike. This case series further prompts the question of whether EOT+ is, in fact, a predictor of treatment failure with DAAs. Prior data obtained from 12 interferon-free clinical trials demonstrated that 55% of EOT+ patients went on to achieve a sustained viral response (SVR) 12.¹

Our group further evaluated EOT+/SVR12 in clinical practice and showed this phenomenon to occur in only 6% of HCV mono-infected patients treated with DAAs.² Furthermore, 100% of EOT+ patients went on to reach SVR12, with EOT+/SVR12 occurring in only genotype 1a/b patients with advanced fibrosis/cirrhosis and by Abbott RealTime PCR assay (ART; Abbott Laboratories, Abbott Park, IL).² Although there remains no consensus on why EOT+/SVR12 occurs, we can definitely conclude that EOT+ is not associated with treatment failure in patients treated with DAAs.

References

1. Harrington P, Deming D, Komatsu T, Naeger L. Hepatitis C virus RNA levels during interferon-free combination direct-acting antiviral treatment in registrational trials. Clin Infect Dis. 2015;61(4):666-667. https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/civ402

2. Malespin M, Benyashvili T, Uprichard SL, et al. Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies. Therap Adv Gastroenterol. 2017;10(1):68-73. http://journals.sagepub.com/doi/10.1177/1756283X16672392

__________________________________________________________________________________________________________________________________________________

HEPATITIS C TREATMENT

HCV viral load levels during treatment and speed of decline do not predict cure with interferon-free therapy

David Wyles presenting at CROI 2015.

Liz Highleyman

Produced in collaboration with hivandhepatitis.com

Published: 23 April 2015

(Excerpts only)

... Conference on Retroviruses and Opportunistic Infections (CROI 2015) ...

... Furthermore, even having low-level detectable HCV RNA at the end of treatment does not preclude a cure, the investigators for a related study concluded ...

Viral load monitoring

Sreetha Sidharthan and colleagues evaluated the ability of HCV RNA levels measured at week 4 and at the end of treatment to predict outcome among 37 people with HCV mono-infection who were part of the SYNERGY study and 50 people with HIV and HCV co-infection who were part of the ERADICATE study and who were treated with sofosbuvir/ledipasvir for 12 weeks (this analysis omitted SYNERGY participants who received one of the triple regimens for only 6 weeks). As noted above, SVR12 rates for this regimen were 100% in SYNERGY and 98% in ERADICATE.

Using the more sensitive Abbott assay with a quantification limit of 12 IU/ml, the majority of participants with HCV RNA >LLOQ, or below the LLOQ but still detectable, at week 4 went on to achieve SVR12. There were five people in SYNERGY and seven in ERADICATE who still had detectable HCV RNA at the end of treatment, and all achieved SVR12. The negative predictive value of week 4 viral load was less than 13%. Looking at people with HCV RNA >LLOQ at week 4 and at the end of treatment, a majority achieved SVR12 and the negative predictive value was >11%. Fewer people had HCV RNA >LLOQ or <LLOQ but detectable using the less sensitive Roche assay.

"Low negative predictive values of HCV RNA at week 4 underscore the importance of continued therapy for patients who fail to achieve undetectable levels of HCV RNA early on during treatment because the likelihood of achieving SVR12 is still high," the researchers concluded. "Contrary to past experience with interferon-containing treatments, the presence of detectable HCV RNA at EOT [end of treatment] is not predictive of relapse in these studies." ...

_________________________________________________________________________

Basic premises (and semantics) that need to be understood, about ... what constitutes SVR12 ... and it is NOT whether you are "UND", it is if your PCR shows that you are "below the lower limit of quantification" (below LLOQ) which for most of us, and the labs we go to, the LLOQ is often either <12 or <15 ...

Phase 3 Harvoni trials used this language ... Sustained virologic response (SVR) was the primary endpoint and was defined as HCV RNA less than LLOQ at 12 weeks after the cessation of treatment. Relapse was a secondary endpoint, which was defined as HCV RNA greater than or equal to LLOQ with 2 consecutive values or last available post-treatment measurement during the posttreatment period after achieving HCV RNA less than LLOQ at end of treatment."

-- Edited by Canuck on Sunday 28th of October 2018 04:38:38 AM

Canuck · Guru

Oh my Mak!

That is a tall research order you are asking for! ... that you want me to find you everybody who has ever been found to be <15 detected at EOT and gone on to be SVR12! (gee - and i thought it was hard enough or a lot of work just to look up some of the folks around here for you on this site who were also not UND by week 4, but went on to be perfectly cured! BTW- did you ever read that post, below, (where i found you some folk around here who were not UND at 4 weeks and were slow to go UND, but yet were cured??) - you rarely respond in depth to the posts we make to you, so i am not sure you have really read them, you often go on and skip ahead to another event.

So, further to showing you names of other people here who did not go UND at 4 weeks or who went UND slowly and still ended up being perfectly cured ... (see in my prior post to you) ...

Here is a post I copied from a nice lady called "Ella", she is from and on another website - she obviously reads studies about this topic of being detected at EOT too. She found one pretty good (related) study (337 people) but specifically a part of the study that spoke about only one person out of 18 who had been found detected at EOT who relapsed.

Here is what Ella found and shared ...

Here's an interesting article from April 2017. It does not include Epclusa specifically (maybe not out then?), but I think it would apply to DAAs generally.

Virological and clinical significance of detectable HCV-RNA below limit of quantification at End-of-Treatment in patients treated with direct antiviral agents
http://livertree.easl.eu/easl/2017/international.liver.congress/168237/ubaldo.visco.comandini.virological.and.clinical.significance.of.detectable.html?f=m3t4035

337 patients enrolled in the study.
16 patients relapsed.
18 patients were detected, not quantifiable (DNQ) at end of treatment (EOT).
All patients DNQ at EOT or 4 weeks post were reanalyzed using an ultrasensitive HCV RNA test (US).
Out of 18 with detectable HCV-RNA with both tests at EOT or PTW4, only 1 experienced relapse.
Out of 16 relapsers, only 2 showed DNQ at EOT (12.5%).

I have also found quite a few studies/articles which are ALL leaning to the premise that "detected <15" at EOT does not (cannot) predict/equate to failure.

The VL has to be done, and will be done again at EOT+12 weeks. And, lucky you, your doc will also be giving you another VL at 8 weeks and at EOT. So, even if the 8 week VL and the EOT VL shows detected at <15, this is still very good news - it is the same good news you have been receiving since you started the Vosevi, which is that you have had a very strong, good, early and robust response to the DAA and I am sure you will continue exactly this same way from now on - you have already succeeded in getting a lovely crashed VL and LFT's, and you have been getting yourself so many VL's done (overall, the private ones and the regular ones) they are ALL showing you that you are remaining/retaining/holding this crashed VL and LFT level. Achieving and holding these levels IS significant. The UND will come. smile

Oh - and so, BTW, I don't really care if your lab says get another test with them OR at another lab - where you get it done likely doesn't matter much (although using the same lab, same equipment, same people is just better in theory and in practice) - the testing, via differing labs, would likely be reliable and very close to one another anyway - the only dif being maybe whether their equipment goes down to >12 or >15, it is only that i thought it an odd comment for the lab to add to their report, that's all. It is likely some dumb "liability" cover-yer-butt sentence they add to a report. shrugs

You SIMPLY MUST discuss your failure fears with your hep doc - we cannot reassure you no matter what proof, evidence we find or say - as far as I am concerned your labs have already proven the Vosevi has whopped the poop out of your load, decimated your infection to smitherines, and that you will be UND and you will stay that way ... ASK YOUR DOC for his advice and opinion.

Later, C.

Cheddy · Moderator

Oh, I remember. You are on your second treatment. No wonder this comes up for you. I have to say, I would probably be feeling the same. Still, I'm sincerely optimistic. Some people say that the early tests are just to see that you are taking your meds, not in fact because they think you will be cured early. Hang in there, brother. We are here to help you get through.

Best to you.

mcmaklin · Senior Member

I hope to be UND soon - I will not be doing anything without doctors knowledge!

Hep C Discussion Forum

(Excerpt only) - for full info see Journal case study

Gastroenterology

Excerpts below are from the current Guidelines:

Section - "Monitoring Patients Who Are Starting HCV Treatment, Are on Treatment, or Have Completed Therapy"

Recommendations for Discontinuation of Treatment Because of Lack of Efficacy

TAKE-HOME MESSAGE

(Excerpt only) - for full info see Journal case study

Gastroenterology

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