Hep C Discussion Forum

JimmyK · Guru

RE: Question Regarding Breakthrough

JimmyK · Guru

mallani wrote:
Just a note of caution interpreting results from the ION Trials.
When they speak about 'treatment experienced' relapsers, they are referring to those who failed either PEG/Riba or PEG/Riba/Incivek or Victrelis. These patients will not have treatment-induced NS-5A RAVs.
Treatment-experienced relapsers after a previous NS-5A blocker are a different kettle of fish. These patients will have treatment-induced (as well as naturally occurring NS-5A ) RAVs.
Just remember that Ribavirin is effective against all known RAVs. Cheers.

Greetings Malcom. I appreciate your input.

With regard to the RAV's this is something that I am confident The Doc is looking at closely. Here is a note from him back on 02/14.

"Your failure appears to be related to a specific NS5A mutation at the 28 position.
This was reported to be sensitive to 24 weeks of Harvoni. However, the data from a large observational study showed that patients who take acid suppression have a worse outcome. If not for this, all patients were cured with 24 weeks of Harvoni UNLESS they had a L30 or Y93 mutation.
I checked with Merck - lower sensitivity resistance mutations (i.e. 28) did not have an effect on outcome. They recommended 16 weeks Zepatier with RBV.
I can't be sure that this is the best choice, but data are currently limited.
We can try 24 weeks Harvoni (I would add RBV).
AbbVie has a new combination that should take care of this mutation - I will have to see when their trials start.
Zepatier may work based on lower resistance for the 28 mutation."

Ok that said the specific mutation in my case is considered to be a. "...lower sensitivity resistance mutations (i.e. 28) did not have an effect on outcome."

When he said, "...We can try 24 weeks Harvoni (I would add RBV).", this is the statement I want to get clarification on. Again I do contracts so exact wording is something I tend to focus on in some cases, such as here. He did not say we can try Harvoini with RBV. He used a parenthetical statement as if to imply if it were him he would add.

I do believe he is focusing to closely on the Omeprozol. He set aside the M28 and noted that only the L30 and Y93 produced failures.

From what I have read the simultaneous use of Harvoni and Omeprozol in fasting conditions eliminates the concern. Personally I believe the difference between 12 weeks and 24 weeks is by far the superior method of eliminating any concerns if L30 and Y93 are not part of the equation. That is how I read the data.

If indeed the M28 is set aside based on it's low sensitivity resistance in a 24 week regiment then I see no actual benefit in adding RBV. If there indeed is a solid and sound purpose than no problem. Kind of like ankle weights. If I was diving I would probably want them. But just for every day walking around? Not so much.

Warm Regards

JimmyK

Gracie · Guru

JimmyK wrote:
Linuxter wrote:
Can't 'splain in medical terms but you could always look at it like Harvoni is the sword and Ribavirin is the shield ...
... doubt that's at all accurate but it makes sense from a Riba perspective ... as I drool and babble on in idiocy ...

Dave
Indeed Dave, not a bad analogy. Provided of course the shield does not become a dead weight only. Then it just slows a Warrior down.
Need one of them :drumroll: smilies here . LOL

If RIBA is the shield, it's a very small shield as the difference between using it and not using with 24 weeks of harvoni is no difference at all in SVR rates up to very little difference. And the sides are much worse, so a better visual might be a very very small shield which you use to repeatedly hit yourself in the head with for 24 weeks.... Lol...

mallani · Guru

Just a note of caution interpreting results from the ION Trials.

When they speak about 'treatment experienced' relapsers, they are referring to those who failed either PEG/Riba or PEG/Riba/Incivek or Victrelis. These patients will not have treatment-induced NS-5A RAVs.

Treatment-experienced relapsers after a previous NS-5A blocker are a different kettle of fish. These patients will have treatment-induced (as well as naturally occurring NS-5A ) RAVs.

Just remember that Ribavirin is effective against all known RAVs. Cheers.

Canuck · Guru

JimmyK,

Riba or not to riba, that is the question? Well, if just any ole person can vote on this, then personally, I would never "wish" riba on you just because I like you. Not scientific. But, then again, I do want to see you get the "just right" goldi-locks regime this time round, again, for same reason, really like ya! Good arguments about lack of data on riba increasing success, and reminds me of syd's rationale with her doc when she wished to increase her therapy from 12 to 24 weeks - where she pointed out to him that there was no data that said she DID NOT need 24 weeks. I tend agree with the head nodders, that riba is cruel insurance, but nor would I wish to do it.

On a sidetrack ... regarding re-treatment for failures (Mallani once wisely advised me on what my likely "pre-built-in" TN RAVs might be, and, to ask my doc "what next", where will I be able to go, if I fail my regime - a question I still do not yet have clarity on from the doc - if I ever get to treatment!) ... but, being that you do have feedback on your RAV's, you probably already have this "re-treatment" question covered, or it is on your list for the doc on Mar 8? Is this too a consideration ... in deciding whether you should or should not add riba to this round? Sof "re-use" has been covered, ledi successes speak for themselves. I did find "re-use" of ledi interesting ... SOMEWHERE on this site (just recently)- I CAN"T FIND IT NOW - EVEN THO I TRIED! - someone posted something about ledi "re-use" in ledi failures - thought it might have been worth reading again - but like I say, I can't find it. Found this tho - prolly won't help. Wish I could help tho! C.

http://natap.org/2015/EASL/EASL_26.htm

Linuxter · Guru

Tig56 wrote:
Okay, I just have to throw this out to brighten up the mood around here. We all have to be honest, "we love Ribavirin" (head nodding), Ribavirin is good (nodding) and I'm crazy as hell (nodding). Yep, I'm nuts, but it's fun sometimes, lol! Hang in there my friends, you're going to whip this. That I'm sure of (nodding again )!!

Right there noddin' with ya Tig ...

Signed,

The guy with the "non-existent" sides

-- Edited by Linuxter on Monday 29th of February 2016 05:36:45 AM

Linuxter · Guru

No ... don't need it bringin' ya down unnecessarily ...

JimmyK · Guru

Linuxter wrote:
Can't 'splain in medical terms but you could always look at it like Harvoni is the sword and Ribavirin is the shield ...
... doubt that's at all accurate but it makes sense from a Riba perspective ... as I drool and babble on in idiocy ...

Dave

Indeed Dave, not a bad analogy. Provided of course the shield does not become a dead weight only. Then it just slows a Warrior down.

Need one of them :drumroll: smilies here . LOL

Linuxter · Guru

Can't 'splain in medical terms but you could always look at it like Harvoni is the sword and Ribavirin is the shield ...

... doubt that's at all accurate but it makes sense from a Riba perspective ... as I drool and babble on in idiocy ...

Dave

JimmyK · Guru

This is why this place feels like Family to me. Honest, direct, sharing and understanding.

Quite a bit of data indeed.

I am at a place where I do not intend to fight for or against RBV. I will follow the final decision of my Doctor either way. But I do intend to fight for the proper substantiation that determines the course of therapy. If RBV is to be added, (assuming that 24 weeks of Harvoni is the way to go), then I want to know why. I want to be shown why.

If it takes being sicker than two dogs to whip the Dragon then so be it. That really is not the issue. Getting sick is something I used to do as a routine every time I was booked into The County Jail. Back then it was simply part of what I chose to do.

Right now I choose to win so whatever it takes, tally ho and all that kind of crap.

I am not cirrhotic. Actually a low end F2. My mutation is the M28 and not the most rabid. All the data points to 24 weeks w/o RBV and the rate is extremely high.

So yes I will add RBV if it can be demonstrated that it actually increases my odds, but it must be demonstrated and not simply a "good idea" based on treatments other than Harvoini. I already know getting me in the place I was is not anyones idea of a "good idea" if they actually have to deal with me. LOL

My current state is an exercise that regardless of the decision reached, it will not be hap hazard in nature but a product of solid reasoning.

Warm Regards y'all !!

JimmyK

wmlj1960 · Moderator

Okay. I'll quit being a killjoy. I was 100% for riba when my Dr said do it. I'm nodding but not like I was when Dr said "no-riba". biggrin

Tig · Admin

Okay, I just have to throw this out to brighten up the mood around here. We all have to be honest, "we love Ribavirin" (head nodding), Ribavirin is good (nodding) and I'm crazy as hell (nodding). Yep, I'm nuts, but it's fun sometimes, lol! Hang in there my friends, you're going to whip this. That I'm sure of (nodding again biggrin )!!

wmlj1960 · Moderator

JimmyK wrote:
When blood was again drawn at roughly week 9 my side effects were rather extreme and it felt like something was not quite right. Even then the test was not read until week 11 at which time they said STOP. By then I was quite a mess physically and mentally. I was attributing it all to 11 weeks of RBV but it seemed a bit extreme in comparison to many here I have been watching. So my question is specific to weather a Breakthrough enhances side effects of RBV.

I was quite a mess a week 11 too Jimmy but the Ribavirin affected me most in the 2nd half of my 24 week Sov / Riba treatment in 2014 and I was UND all the way to EOT. I was just looking back over some of my old post and see where, at week 11, I described the Riba Sx 's as "that lonely 'The World Against Mike' feeling". The depression got me worse than the irritability. The fatigue really set in during the second half too.

I am cirrhotic / co-infected and that makes a big difference and my case was abnormal as I underwent 3 major surgery's at 16 weeks for broken back and other bones and arm amputation and was still in the hospital recovering @ EOT. My hepatologist at the liver transplant center where I was being treated for HCV was taken out of the picture during this time because I was under the care of the Orthopedic surgeons at the trauma hospital. They evidentally were not very concerned with the ribavirin effects and also I was pushing to stay on the full dose of riba the whole time. It's amazing how much some of us will put ourselves through to rid ourselves of HCV.

This doesn't exactly answer your question because my breakthrough was after EOT, but the ribavirin effects stay with you for an extensive time after EOT and my condition went way downhill during that time after breakthrough. My Hgb had stayed above 9.5, RBC 2.64 during Tx. Then they had to amputate my leg due to post-op infection at EOT+4 week at which time my Hgb was 7.2, RBC 2.04 and HIV CD-4 169, and it was a good thing I was confined to a bed because I didn't have the energy to stand up if I could have.

I agree with why not add ribavirin if it will increase your chance of achieving SVR but when my hepatologist choose to re-treat me with 24 weeks Harvoni (NO Riba) I didn't argue at all. After all I had been through with ribavirin just to fail treatment I just didn't think the Sx's vs the unproven advantage would be worth fighting for. I won't know until April whether 24 wks Harvoni (No Riba) worked for me, but if not, It's good to know that these latest Riba-free regimens are having such good success. My circumstances were unique and pretty drastic but after my treatments with both riba/no-riba I'd rather do 3 - 24 week Tx's without riba than do 1 - 24 wk Tx with it. JMO smile

Linuxter · Guru

Hi Jimmy,

This Article does not address "Increased Side Effects due to Breakthrough" but does analyze one study about the addition of Ribavirin to Harvoni and mentions specifically Genotype 1a and breakthrough patients as part of the study. At the bottom of this article is the Reference. (Do note the potential for conflict of interest which may or may not have effected this study ... i.e. Take it with a grain of salt and perhaps find additional studies that may or may not support these findings.

Edit: Please Read THIS POST which sheds light on this study and the use of Ribavirin in conjunction with DAA's (Thank you Malcolm)

Dave

-- Edited by Linuxter on Monday 29th of February 2016 08:57:41 PM

mallani · Guru

Hi Jimmy,

Although absorption of Ribavirin is rapid, it takes about 4 weeks to achieve steady-state plasma levels. This is why most patients don't have any side effects for the first 4 weeks.

As the plasma concentration increases, more Riba is transported into RBC's. The Riba anaemia usually shows itself from 4 weeks onwards.

In the old SOC days, it was quite common to measure plasma Riba levels. For some patients, this never reached accepted levels. These patients had a minimal drop in Hb, and usually had breakthrough or relapse. The low plasma levels were thought to be due to a lack of the transporters, and was particularly noticed in patients taking a lower Riba dose. Weight-based Riba gave better SVR chances than the standard 800 mgms/day.

So, in answer to your first question, breakthough does not have any effect on the side effects.

The PPI's, like Omeprozol, have a minimal effect on the absorption of Ledipasvir. This reference suggests the plasma level may be reduced by ~10%, which does not effect the chances of SVR.

http://www.natap.org/2014/Pharm/Pharm_04.htm

As a relapsed cirrhotic, I'd want 24 weeks of Harvoni and Riba. Cheers.

Shadowfax · Guru

Hey Jimmy,

I wish I had some answers but I wanted to chime in to say you have been very supportive and informative to many. You are in thoughts and prayers for this to work. You will clearly be well armed to tell your doctor what you have learned and challenge anything that does not seem right based on the information you are collecting.

Wishing you only the best and will be watching for your post after your appointment.

JimmyK · Guru

Hiya Scruff and thanks much!

My counts did go down and entered the area where low but it was no plummet that is for sure. That happened between 11/17 and 12/15. My sx were a combination of no sleep/weight loss (25lbs)/extreme muscle pain/and a side order of insanity.

I was allowed to work from home and still am. I will continue to do so through treatment but I will need to get a solid grip on anger and outburst issues that can cause an unsuspecting person to kind of soil themselves.

At treatment stop they actually had to give me light dosage of Norco for 20 days and whereas it did not particularity ease the pain it did make it where I was a bit more "who cares" about it.

JimmyK

JimmyK · Guru

Gracie wrote:
Hi,
I failed treatment twice ... Int/RIBA and Incevik triple. Both times I had RIBA. At 8 weeks last treatment I was und. Sometime between 8 and 12 I relapsed. The symptoms never changed much so I wouldn't think your worsening was from the virus itself, but rather the RIBA wreaking havoc on your blood levels.
My hepologist said with 24 weeks of harvoni RIBA was not needed. And she also told me I could take omeprazol as long as I took it at the same time as the harvoni. She said taking it at the same time would cause no issues with the effectiveness of the treatment, and adding RIBA would not give me a better chance of success for 24 weeks. Only with 12 weeks. I didn't take the omeprazol mind you, and never had any stomach issues to speak of during treatment. But I did have it here in case my stomach issues came back. Harvoni actually made my stomach issues decrease which was odd but nice. Maybe it was all that DQ ice cream that soothed the tummy.
I think since you had such an adverse reaction with the RIBA, 24 weeks of harvoni alone would be your treatment of choice. Speaking from somebody with the same type of history. But make sure you go to the doctor with your list of questions so you make the best choice for you.

Thanks much Gracie!

This is exactly where I am headed. The data supports your Doctors conclusion, and your UND status does as well.

JimmyK

JimmyK · Guru

Tig56 wrote:
Hey Jimmy,
I'm unaware of their being a correlation between the use of Ribavin and a subsequent increase in felt adverse effects following a breakthrough. More than anything, the side effects from Ribavirin seem to affect everyone when they initially prescribe it on a weight based calculation. Knowing you're a big dude, I'm assuming you received 600 mg twice daily. Yes/no? That dose clobbers everyone and it was particularly tough on me throughout treatment and for a full year afterwards. If there was a side effect, I had it. Now one consideration you can investigate is whether you need to be on a weight based dose. Some reports I've read indicate a much easier ride on lower doses, such as 800mg. Put that on your list of questions
I believe your odds of success on 12 weeks of Harvoni are good and 24 would be stellar. You can find results that indicate routine to improved benefit from the addition of Ribavirin's inclusion in the Harvoni treatment. I would start a list of questions and thoughts prior to your meeting on the 8th and in the meantime we can assist you in finding more information on everything pertinent to the discussion.
http://ipsite.org/3f8w
http://www.news-medical.net/health/What-is-Ribavirin.aspx

Greetings Tig,

1st thank you for the time spent on a well thought out response. I tend to agree that there is likely no connection to the Breakthrough. That said however I don't think that RBV is a good idea for me. I have kept rather quiet of some of my experiences as not to dissuade anyone else from using it or spooking them. Each person is an individual and this is not a one size fits all kind of thing with regard to side effects.

The 12 week Harvoni may see a measure of improvement with RBV but slight at best. The 24 week I am convinced RBV is not helpful nor needed.

I appreciate the links and the tend to support my conclusion.

I am absolutely going to be requesting the 24 weeks and I believe he will support that. I will need some absolute justification on adding any degree of RBV to that when the data says it is not helpful.

JimmyK

Scruffy · Guru

Most likely the riba Jimmy. The riba takes a little time to build up and do its thing (which include sx's) At week 7 I felt a little "off" well maybe a lot off. Doc looked at the blood test and sent me right on the spot to the ER for a transfusion. I would guess it was just the riba causing you to feel like that and not the virus.

Best wishes for your new tx.

Gracie · Guru

Hi,

I failed treatment twice ... Int/RIBA and Incevik triple. Both times I had RIBA. At 8 weeks last treatment I was und. Sometime between 8 and 12 I relapsed. The symptoms never changed much so I wouldn't think your worsening was from the virus itself, but rather the RIBA wreaking havoc on your blood levels.

My hepologist said with 24 weeks of harvoni RIBA was not needed. And she also told me I could take omeprazol as long as I took it at the same time as the harvoni. She said taking it at the same time would cause no issues with the effectiveness of the treatment, and adding RIBA would not give me a better chance of success for 24 weeks. Only with 12 weeks. I didn't take the omeprazol mind you, and never had any stomach issues to speak of during treatment. But I did have it here in case my stomach issues came back. Harvoni actually made my stomach issues decrease which was odd but nice. Maybe it was all that DQ ice cream that soothed the tummy.

I think since you had such an adverse reaction with the RIBA, 24 weeks of harvoni alone would be your treatment of choice. Speaking from somebody with the same type of history. But make sure you go to the doctor with your list of questions so you make the best choice for you.

Tig · Admin

Hey Jimmy,

I'm unaware of their being a correlation between the use of Ribavin and a subsequent increase in felt adverse effects following a breakthrough. More than anything, the side effects from Ribavirin seem to affect everyone when they initially prescribe it on a weight based calculation. Knowing you're a big dude, I'm assuming you received 600 mg twice daily. Yes/no? That dose clobbers everyone and it was particularly tough on me throughout treatment and for a full year afterwards. If there was a side effect, I had it. Now one consideration you can investigate is whether you need to be on a weight based dose. Some reports I've read indicate a much easier ride on lower doses, such as 800mg. Put that on your list of questions

I believe your odds of success on 12 weeks of Harvoni are good and 24 would be stellar. You can find results that indicate routine to improved benefit from the addition of Ribavirin's inclusion in the Harvoni treatment. I would start a list of questions and thoughts prior to your meeting on the 8th and in the meantime we can assist you in finding more information on everything pertinent to the discussion.

http://ipsite.org/3f8w

http://www.news-medical.net/health/What-is-Ribavirin.aspx

robertsamx · Guru

Hi Jimmy! I"m going to think out loud here. I wonder if reducing the amount of Riba taken each day would give positive results in controlling s/x and still help kill the virus?? RC

JimmyK · Guru

Greetings Y'all,

As I contemplate options and in preparation for discussing the same with my Doctor on 03/08, I know one of the options on the table is Harvoni x 24 weeks.

I know that my Doctor if he agrees will want to add RBV. That due to the fact I take Omeprozol.

What I am not sure of because I have never seen it discussed, is if during a Breakthrough, are side affects enhanced? Back ground: I was doing 12 weeks V-Pack and RBV. At 4 weeks I went from 3.8m VL to 115. Up to that point the side effects were there but not that big of a deal. Sometime after the 4 week test results I had a Breakthrough but blood testing was not as on target as it should have been. When blood was again drawn at roughly week 9 my side effects were rather extreme and it felt like something was not quite right. Even then the test was not read until week 11 at which time they said STOP. By then I was quite a mess physically and mentally. I was attributing it all to 11 weeks of RBV but it seemed a bit extreme in comparison to many here I have been watching. So my question is specific to weather a Breakthrough enhances side effects of RBV.

The reason I am asking of course is if the Doctor says ok to 24 x Harvoni on the condition I also use RBV will the effects be as extreme as the 11 weeks was? Is he justified in the addition of RBV based on my taking Omeprozol? If so where is the data for that?

I also have added two slides.

The first is Table 4 of the Harvoni dosing guidelines. That Omeprozol can be used is clear but it is also clear it can have an effect on the concentration of Ledipasvir. What I do not see is the data that shows the level of effect.

The second slide is the ION II Study table in cases like mine where treatment has failed. 12 weeks if non cirrhotic produced 95% SVR and 24 weeks produced 99% including 22 out of 22 cirrhotics at 100%. n=109 in each study so not small and specific to repeat offenders.

It is also noted that RBV regarding both of these arms was NOT USED and in fact stated that RBV was NOT shown to increase response.

Because the 12 weeks is what is recommended in my case, I would assume that any concerns regarding Omeprozol should be swallowed up in the 24 week course without RBV.

I know there is a lot of support here for RBV and I am not saying the stuff does no good. But in my case it is a bit on the extreme side unless that was simply part of the Breakthrough response to it., and hence my question.

Thanks Y'all

JimmyK

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