EPCLUSA ~ Am I failing?

[V.BiTheSea]

My doctor believes my sub-optimal lab results indicate a poor outcome for me in achieving SVR. He urged me to stop treatment a month in when I reported severe muscle and joint pain. (I told him 'No way!')
In fact, there is increasing evidence that early response on treatment predicts the likelihood of cure in G3 patients – patients who clear the virus slowly during therapy are more likely to fail treatment.
I just got latest lab work back this morning and although numbers remain on a downward trajectory I am STILL DETECTED at almost 7 weeks in. Researching this board for those with G3 on Epclusa, I found only two people who remained detected at 4 weeks and they both went on to clear at next test.
I'm getting a referral to a Dr who is more of a Hep specialist than the one I'm seeing. I hope I can get the Epclusa extended to 24 weeks, but so far there are no completed studies I can find that would support such an extension.
I'm left on the one hand despairing, full of anxiety, and depressed that I may be in the unlucky 2% of treatment-naive people for whom this med will fail. (F**K!) On the other hand I have more energy now that VL is less. I noticed my eyebrows are turning gray all at once! This is so stressful!!!

[elias]

Hi again V. by Sea:

Sorry about what you're going through now.

I think the basic assumptions leading your doctor to expect treatment failure here are not that accurate. While many do clear HCV during first 4 weeks of treatment, many do not. Whats looked for is at least a 2 log drop in viral load early on, and you did achieve that. Early response was more of a prognosticator in the Interferon days. Not anymore.. Maybe that is what your current physician is using as a paradigm..

In fact, some dont even clear it by EOT , yet go on to achieve SVR by week 12.


See here. I know its about GT1, but was written up before Epclusa was in use:

https://academic.oup.com/cid/article/60/12/1743/2462593/Utility-of-Hepatitis-C-Viral-Load-Monitoring-on


GT3 is tricky for those with cirrhosis, which you do not have. I've never seen where severe side effects are suggestive of imminent tx failure.

It's good you're going to a new specialist. Hopefully, he can help sort this all out. And is more up-to-date with these newer meds. And if extending Epclusa to 24-weeks is a desirable route at this point....

I realize this must be scary. I'm going in tomorrow for my EOT+12 week test and my mind is playing out all sorts of scenarios

BUT: In the unlikely event Epclusa fails for you, there are two highly effective meds for treatment failures on fast-track fro approval by FDA this summer. I posted about those in the Research Section of this forum. But first see what the specialist you plan to see has to say. Try to be sure up front he has experience and is up to date with the newer DAA's

By the way:

How are those side-effects you had a few weeks ago? Gotten any better?

Best wishes

~elias

[elias]

Wasnt sure i should post this. But..

On your signature line for April 11:

"4-11-17   VL <15  Log <1.18
               ALT 30   AST 25

My own UNDETECTED Nov 22 report also reads:

HCV RNA<15
 HCV RNA< Log 1.18
 UNDETECTED.

You definitely decreased your viral load from 4 weeks to the 7 weeks. But what reference does your lab have for lowest level of quantitation?

Is it possible you're already undetected?

[Lynn K]

I agree your 4/11 viral load looks like either you were not detected or weekly detected. Was there in addition to the numbers either the words "detected" or "not detected"?
We had a couple of people here that treated with Harvoni and were weekly detected at end of treatment and even at 4 weeks post treatment but were eventually not detected 12 weeks after treatment ended which is considered cured. One member here may see this post Dragonslayer he remains cured now 2 years post.

There are no recommendation to discontinue treatment due to still being detected your doctor may be thinking of the old interferon treatment days.

You have made a good division to seek out a doctor more experienced in treating hep c I doubt they will say anything other than to continue your treatment.

The only test that matters is the 12 week post treatment test. On treatment testing is of little to no value. On treatment testing really only serves to cause unnecessary worry as it has done for you.

The odds for you are still very good believe it.

[V.BiTheSea]

The test results as reported above are FLAGGED "A" for ABNORMAL with following:

Hepatitis C RNA viral load below the lower limit of quantitation (15 IU/mL),
but above the lower limit of detection for the assay is present. Unable to
determine viral concentration in the sample. Repeat testing may be warranted
as clinically indicated.
The quantitative range of this assay is 15-100,000,000 IU/mL (1.18-8.00 Log
IU/mL ).
This test was performed using the COBAS AmpliPrep/COBAS TaqMan HCV test kit,
version 2 (Roche Molecular Systems, Inc.).

[Lynn K]

That sounds like your viral load is less than the LLOQ (lower limit of quantification)  which is the lowest quantity of virus that the test is able to determine the quantity of.

That would be a viral load of less than 15 but detected.  I don't recall what Dragonslayers viral load was on treatment, at the end of treatment, and four weeks post treatment but it was higher than 15

[V.BiTheSea]

Hello elias! I will be sending all my very best wishes your way for your appointment tomorrow. Can't wait to hear how everything turns out; sounds like you are on track for a sterling report!

Are you getting any sleep lately? Have your sleep patterns changed as you've progressed through the meds, or is it all pretty much the same as before?

A big thank you for posting re the treatment-resistant meds. I thought I was at a dead-end if the Epclusa didn't work as I had read somewhere that Gilead was no longer interested in working to invest more time and money with the unlucky 2-5% since they have had such major success with the other 95%! I haven't read the articles yet, but am feeling hopeful just hearing about them. I have been in a downward spiral these past weeks and am much cheered by your recent posts.

[Lynn K]

The AASLD ( American Association for the Study of Liver Diseases) is a clearing house for medical research on liver disease along with the different hepatitis viruses.  There are many many researchers involved with finding ways to cure hepatitis C other than Gilead pharmaceuticals.

There were a few here who failed treatment but were  subsequently retreated and later cured.

 I am confident you are not done yet that this treatment will work for you but even if it doesn't, medical researchers will find a way to cure the unfortunate few who weren't able to be cured with present methods.

I failed a 12 week treatment with Sovaldi and Olysio in early 2014.  I was found to have relapsed 12 weeks after I completed treatment in September 2014.  In October 2014 harvoni was approved. I began treatment with harvoni in November for 24 weeks plus with the addition of ribavirin. I was cured on my second treatment with the new DAA's my 5th treatment in total.

If I can be cured you can be too.

[V.BiTheSea]

Thank you Lynn K. I was such a wreck this week. Trying to talk myself into taking the Riba, which I am Deathly Afraid of and which I KNOW this 'new' (I saw him once but he changed out of my group) Dr is going to suggest. When I saw him initially he wanted to start me on the Harvoni and Riba but I had already found out about the Epclusa becoming available and opted to wait.

Because I have no liver damage I never thought I would be eligible for treatment at all, and was shocked when I found out this year my insurance would cover it and another organization would pick up the difference. I feel as if I have been given a Mega Gift, and I will always be grateful, no matter what the outcome.

[V.BiTheSea]

Wow, Lynn K, what a terrible time that must have been for you.

This stuff is nerve-wracking, to say the least.

I didn't know about the other interests in helping 'poor responders', and that is heartening.

Thank You!

[elias]

Hi again V.

That 1-2% you fear being among is about viral relapse. Which means one cleared the virus while on the Epclusa-- but relapsed once off it. So that's not whats going on here. 

Not clearing it in the first place --non response-- while on it..I have not come across that at all in any of my readings on Epclusa. (Unless you're about to make Epclusa history..)

 But in fact you are responding. By 4 weeks , dropped a few logs; by 7 weeks, moved to below LLOQ. So that it is  now non-quantifiable. You're only a bit over halfway through your Epclusa treatment.  Half the tx protocol still lies ahead..Once off it for a while, you can repeat this test. If you like. It will either be UNDETECTED (likely) or at a much higher n very quantifiable level as HCV replicates very rapidly.

Viral relapse is highly unlikely for you. There's now some outline of a profile for relapsers. And u don't fit that profile..Doesn't mean it cant happen, but

It could be that what that most recent vl test picked up was fragments of killed virus. "shadow virus" One of the 2 theories put forth on this. I think it's mentioned in the article I linked to.

In unlikely event u need to re-treat best to be in care of dr who would have best sense of which approach to use for that.

Gilead might be done with R&D for newer DAA's. But the one expected to be approved this summer (Sof/Vel/Vox) is believed to be capable of "mopping" up what prior treatments have failed. And  Abbvies' is even better.  Yet a third one is in the wing. Since you're at such low fibrosis level, waiting for those is less risky.
====

My sleeping pattern is still a mess..Will post more on it. Good luck n try to keep hopeful

[elias]

V. wrote:

When I saw him initially he wanted to start me on the Harvoni and Riba but I had already found out about the Epclusa becoming available and opted to wait.

Since when is Harvoni used for for GT3? And why the need for Riba, since you're F0? Prior to Epclusa, I think the advised tx for GT3 was Sofosbuvir+Daclatasvir

In any case, its good youre trying to get input from another specialist on this. Hope you got your 3rd bottle on hand already

[V.BiTheSea]

I DO have my third bottle on hand and am on track to start it in five days from now. I've been careful to keep it unopened because I thought I might have to be returning it and wanted to make sure it was considered fit for use by someone else.

After reading comments here yesterday I am hopeful to be putting it to good use myself. You're right, my labs ARE showing a good response, which I pointed out 3 times during my office visit by Dr was decidedly unimpressed! He was all like, “This is bad news”, and “Genotype 3 is the hardest to cure”, and if the VL rebounded at all I should should quit “right away” and suggested I might go to SF for treatment.

So good for me that in the depths of fresh despair I instinctively ran here to tell my sad story. Well, it was like climbing out of a dark pit and finding myself in a sun-filled library where people know a lot, have been through a lot, and care enough to tell it like it is. I have so much to be grateful for, and finding my way to you guys is high on my list.

The first office visit I had was more than 2 years ago, and I might be dead wrong about exactly what he wanted to prescribe at that time ~ might not have been Harvoni at all, but I'm very sure about the Riba component because I can remember the blood draining from my head when I saw the name on the packet he brought in. Lucky I had read something about the Epclusa being on deck for approval, because it sounded so much better to me.

I can't wait to hear about elias' update today, but not exactly sure where to look. This is a big site, and I'm still trying to find my way around. Sending you good energy from a beautiful day in CA!

[elias]

Hi again V.

I wont know results of viral load i took today until next Thursday earliest. Because of  holidays. if you click on my user name, u can find my latest posts.

As Lynn pointed out, the purpose of viral load testing during treatment is to assess patient compliance, and rapid vs slow response during treatment has little bearing on the final outcome. It's very hard for us as patients to come to grips with this. But it makes it much harder if the prescribing physician doesn't realize this either and operates under the older interferon paradigms.

It is true that the test which matters most is the EOT+12 week test.Which I took today.   Some do take the test 4 weeks after completing treatment. Because if "not detected" then, much lower chance of viral relapse by EOT12. About 70-80% of those who relapse eventually, will do so by week 4 after EOT. I did take that test ~5 weeks after EOT, and was "not detected" then. I took it because I hoped a "non-detect" the would help my sleep some by some degree of reassurance. The doctor today seemed to think I'm assured good outcome. But I have hard time with all this. So the wait goes on for me...

As for newer medicines for re-treatment in case of failures, the best summary for that I've come across is the following symposium podcast. Based on presentations the AASLD 2016 Liver meeting in Boston. The panel are very high level researchers in HCV and have published extensively. So I trust it. The key info on re-treatment protocols are in the first half of this fairly long podcast. So in case you get anxious about "viral failure" again, might help to listen and have a look at those charts they show:

http://hosted.medipix.com/aasld2016/

[Lynn K]

From what I have read if not detected at 4 weeks post the odds of making it to 12 weeks are closer to 95% and at SVR12 the odds of remaining hep c free are 99.8% and that the primary way we would ever test positive in the future would be from an entirely new infection.

[V.BiTheSea]

The same day I started this thread I wrote to FixHepC.com. Here is the reply I received yesterday, along with the some of my answers which I returned as requested. There is also an Addendum sent later by me that I included here.  I really appreciate that this kind Doctor took the time and interest to reply to my e-mail. (I am not publishing the physician's name because I have not asked permission to do so).

Dear Dr
Thank you for your reply. I have answered your questions below...


On Apr 16, 2017, at 1:46 PM, FHCBC <help@fixhepc.com> wrote:

Hi Vickie,

Yes, it's not great. Not hopeless and I can tell you that 75% of people still detectable ie <15 at the end of treatment will still go on to SVR12

I am presenting that little factoid at EASL next week.

I am also presenting 2 other bits of relevant data

1) 12 weeks is not enough for GT3. Full stop (at least with Sofosbuvir+Daclatavir) and this is because the kinetic decay (how fast it goes away) is not fast enough for it reliably to be all gone by 12 weeks

2) Patients who are still detected at the week 4 test have a 1.91 - 2.5 times greater risk of relapse. 44% of our relapses had this profile versus 22%.

So first is this is Gilead Epclusa or a generic? If a generic which brand?
  *Gilead EPCLUSA  Sofosbuvir and Velpatasvir   4000 mg/100 mg   

Next - how long a treatment is planned/how long have you got to go?
 * 1 Tablet Daily For 12 Weeks  Treatment Started 2/21/17

Next - which country are you in? USA?
  *USA

Next - are you taking any other medications/supplements?
   *Amlodipine 10 mg/Benazepril 20 mg Daily  * Hydroxyzine 25 mg Daily   *HYDROcodone/acetaminophen 10mg/325mg Tab As Needed   *Melatonin 2.5 mg Daily   
  *Tumeric   *Vitamin B Complex   *Multi Vitamin   *Vit D3   *Algae Omega   *Magnesium Malate   *Hyaluronic Acid   *Swiss Kriss Lax 

Finally is your doctor going to the EASL ILC in Amsterdam this week? Or what is his name and from where - I can look it up.

**************** ADDENDUM TO MY REPLY OF APRIL 16
                      I HAVE A LONG HISTORY OF FIBROMYALGIA SYMPTOMS SIMILAR TO THOSE EXPERIENCED AFTER EPCLUSA 10 DAYS IN.
                      THE MUSCLE AND JOINT PAIN AND FATIGUE WERE MUCH WORSE DURING EPCLUSA THAN EVER BEFORE.

[elias]

Hi V.

Here is presentation at EASL  ILC 2017 which  possibly indicates differently:

http://livertree.easl.eu/easl/2017/international.liver.congress/168237/ubaldo.visco.comandini.virological.and.clinical.significance.of.detectable.html?f=m3t4035

"Results
Patient were on Metavir F4 (68.6%) or F3 fibrosis (22.8%) or liver transplanted (16.6%). HCV genotypes were 1a(29.7%), 1b(33%), 2(9.2%), 3(16.3%) or 4(11.6%).

Overall, 16 patients experienced post treatment HCV relapse (4.7%).

The frequency of DNQ samples progressively decreased during and after treatment (p<0.0001, Fig.1) and was not associated to any specific DAA regimen, HIV infection, liver transplant or Child-Pugh class.

A significant association was observed between DNQ and F3 stage only at PTW4 (p<0.001).

"Results obtained by US test are shown in Table 1. Only a single patient out of 18 with detectable HCV-RNA with both tests at EOT or PTW4 experienced relapse. Out of 16 relapsers only 2 showed DNQ at EOT (12.5%)."

DNQ=Detected not Quantifiable. Here its referring to such a reading at EOT.
(Yours was much earlier at 7 weeks..)

One out of 18 failures for those DNQ's is approximately~ 5.5% failure rate, which is not significantly different from others with those same protocols of DAA

Also consider: In that communication via fixhep c:

2) Patients who are still detected at the week 4 test have a 1.91 - 2.5 times greater risk of relapse. 44% of our relapses had this profile versus 22%.

Possible confounding variable of cirrhosis in relapse. Did he control for that possibility?

 

[elias]

duplicated posting accidentally

[Lynn K]

Just wanted to make a comment about where you said you were keeping the bottle sealed in case you were not going to take it so you could return it.

Actually once you receive the medicine you cannot return it. 

Unfortunately ,the only thing that legally can be done with medicine that you received is for it to be disposed of

[V.BiTheSea]

Lynn K ~ I had no idea if a med bottle was clearly unopened, that it would be unlawful   
              to use. What a  waste!  I am just in the process of learning there is a network f   
              or generics and perfectly good meds as described to be salvaged for people to
              benefit from. Thank you so much for the info.

               

[V.BiTheSea]

elias ~ The new EASL study you posted is THE one, after much searching, I thought must not yet exist. You are so very excellent. There may come a time in the VERY near future when I will cite this work in my own defense for continuing treatment, wherever that may be headed.

[Lynn K]

In the US once meds are dispensed the pharmacy cannot take them back to prescribe to another patient. They have no way of knowing what may have happened with the meds once out of a controlled situation. You are also not permitted to sell or even give away meds prescribed to you to another person so say if you had some prescription pain med and had some left over legally you cannot give them to your friend. That would be dispensing medication without a license.

Not sure how the networks are allowed to recycle meds or even if they are really allowed to. Of course I understand and appreciate the motivations of such groups but please be cautious about what is going on with that.

[V.BiTheSea]

elias hello 

Awesome news re your test report! I am so happy! Congrats!

(I could not find a post from you, but read it with your profile update.)

How are your feeling???  What are you thinking???