Genotype 1A or 1B - does it matter anymore?

[hepcandme]

My doc says that the new treatment regimens do not differentiate for those with Genotype 1A or 1B. This seems to substantiate that assertion:

http://www.medscape.com/viewarticle/823549#1

I am also wondering why anyone would add Riba to the  ledipasvir and sofosbuvir combination since it doesn't seem to improve outcomes?

And, thoughts on 12 weeks vs 24 weeks?

Looking to begin a new treatment just as soon as the FDA approves this combo

[nan535]

My husband completed treatment (Sovaldi + Ribavirin 24 weeks) 4 days ago.
We're praying for SVR but given his overall history with this virus, we are preparing for the worst - relapse. His backup plan is this combo pill. He too is 1a.

The article you cited includes the following:
"Results were similar for patients with hepatitis C genotypes 1a and 1b. Those with cirrhosis did slightly worse, with SVR12 rates of 86% with ledipasvir and sofosbuvir and 82% for ledipasvir and sofosbuvir with ribavirin. However, SVR12 rates were 100% in both treatment groups with cirrhosis at 24 weeks, Dr. Afdhal reported.

A total of 11 patients relapsed after treatment. All were in the 12-week treatment group, and 7 had cirrhosis, he said."

It seems to be there is some risk then in just doing the 12 weeks if you have cirrhosis. With 100% SVR12 in patients with cirrhosis at 24 weeks, I would think that would be the way to go if a patient has relapsed on a prior Sovaldi treatment.

I'd like to hear others thoughts on this as well.

Nan

[hoping4cure]

Remember when it comes to the patients that have cirrhosis in these clinical trials they are cherry picking cirrhotics with numbers that fall into a certain  group looking at numbers like platelet counts so they can come up with good outcomes and SVR numbers. It looking like the 12 week triple so/led with with or without ribivarin or 24 weeks with so/led will be three of the options Probably can make a good case for those that have failed the so/oly combo for to go for the 24 weeks. The last I heard the so/led 24 week treatment is supposed to come in at a whopping $224,000 per treatment. Yikes!! I was approved for so/loly for 24 weeks so the insurance companies will consider it.

[hepcandme]

Hi Hope!

Does this mean that you are already testing the waters on the new treatment with your insurance company?

My Kaiser doctor told me to be patient. That we don't know exactly what the landscape will be after October 10th (or when it will actually be available after approval) but I sure would like to be ready to go just as soon as the FDA approves

Nan, I am still pulling for your husband to achieve SVR! It must be nice to be done with treatment so hoping he is feeling better and sending good thoughts to the both of you

[hoping4cure]

I'll be testing in less than two weeks for my 12 EOT on Sov/Oly. I was surprised to see that BCBS had no problem approving me for 24 on the Sov/Oly treatment. Doc didn't think I needed 24, I did or at least go out to 16. I guess he was concerned with an advanced patient going 24 with so few treated and with so little published data plus given the fact that the sov/led combo is just around the corner.

[hoping4cure]

That's 12 week post EOT so as to not confuse anyone who might read this.

[hepcandme]

Well, hoping that you achieve SVR with the Sovaldi/Olysio combo and that you won't need the new treatment!

So many have done so. No reason to think that you are not among them

The Heppers, the people who brake for test results. LOL

Seriously, I have pulled my car over on the freeway to check my lab results on my phone

[nan535]

Thanks for the kind wishes for us.  I am praying he gets to SVR and won't need this new treatment but as his caregiver, it is better to always have Plan B in place just so you don't fall apart when you get bad news.  Unfortunately, my husband's road has been a really tough one for both of us and being prepared for anything that may come along helps to relieve the stress level.  
Right now we are just enjoying his being off treatment. We restarted the Xifaxin and its already helping with the HE. (For those who are unaware, his HE actually worsened while on Xifaxin and Sovaldi/Ribavirin).

As I have said before, this community has been a godsend for me not only for the excellent information I have learned but also the very kind support through it all.   Thank you and best wishes to all to one day soon putting this all behind you.

Nan

[Willy50]

I could not access the link without logging into medscape,
but I can tell you that I disagree with the blanket assertion of the doctor.

The answer is the the doctor is correct for some groups of patients and incorrect for other groups.

First, understand that 1a is generally considered to be tougher to treat than 1b in current and soon to be approved treatments.  We see that in SVR rates in many drug treatments, both approved and in trials.

We also see that naives are considered to be easier to treat, and those with lesser amounts of liver damage.

For the easier to treat groups, yes there may be little difference, but as one moves towards harder to treat, I feel that there becomes somewhat greater differentiation.

In a very general sense the doctor may be correct, or close to it.
But if one is parsing percentages, one needs to compare whether the patient has treated before, the level of liver damage staging, and the actual treatment.

There are distinctive response rates for all of these and they are statistically significant IMHO;

They may decide which drug treatment plan one considers in the future (Gild vrs Abbvie /ENTA)

The duration of time one treats (8 weeks versus 12 weeks with respective treatments)

The inclusion or exclusion of ribavirin.

and the variables affect the ultimate SVR rates.

....... the answer is that it all depends on the patients particulars, IMHO

======================
(quote)
"I am also wondering why anyone would add Riba to the  ledipasvir and sofosbuvir combination since it doesn't seem to improve outcomes? "

My answer to that is that it is true for naives with low damage staging with Sov/Ledi, and it is incorrect for most past treatment failure cirrhotics with the same treatment; they will likely require 12 weeks with ribavirin in either the soon to be approved Gilead treatment or the Abbvie/Enanta 3-D treatment (and the 1b's will still likely have higher success rates in all groups, irrespective of treatments or liver staging)

That is the information that I keep seeing. Perhaps someone will correct me if I am wrong.

Willy

[Willy50]

http://www.natap.org/2014/EASL/EASL_27.htm

http://www.natap.org/2014/IAC/IAC_06.htm

http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Sovaldi_GT1.pdf

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=96696670

I cannot put my hands on the cure rates with sovaldi/ledipasvir G-1a vrs G-1b, (many of their results blend 1A's and 1B's
but there is a difference with the Abbvie 3-D treatment, and we also see other clinical trials where only 1b's are treated (which comprise roughly 1/2 of the G-1 population in the USA)

I think the answer still comes down to the patients particulars and which treatment is being considered. I think it doesn't matter what the general response is. You want your doctor to evaluate YOUR chances given your particulars (race, treatment history, liver staging, etc) and plug in what your chances are on any given type of drug treatment.

willy

[sue4hula]

I just read that your husband had you have just finished his treatment regime very recently.  I just wanted to take a minute and thank you.  You have been a great support to me and others on this board.  Thank you for your advocacy.

More importantly, I want to thank you for your support to your husband.  My husband has walked with me every step of the way since I was diagnosed in 98.  Having a partner who walks this walk without wavering ( at least in front of me) gives me strength, courage, and hope.  You are a powerful woman and i understand the walk of the support person/caregiver is not always easy.  

Praying for SVR for him, for you, for me and my husband and ALL whose life is impacted by this virus!

[patra_]

Nan:  I repeat what Sue said.  I have been blessed with a husband who has been/is ther for me, taking an active part in my care and in watching for changes, symptoms, so Like Sue, I KNOW  how much that means.  God's greatest blessings on you for your support to your huaband;also for all the sharing, cheering, advising to all od us.  Wishing y'all (and I do mean y'all) SVR.

Sue:  That thank you also goes to you for your active support and info on here.  Also thanks to our spouse for being there.

Hepc:  SVR is in all our futures, if not now, then before too long.  Hang in there.  

[hepcandme]

thanks for the links, Willy

very informative

My doc may have been speaking for me - not all who are considering treatment

Now that I am a null responder, I'm guessing that the Riba would more than likey be recommended? I know I should not keep thinking "what if" but what if I had tried 24 weeks instead of 12 with the S/O?

And I am concerned that the new treatments will still be considered off label without a larger data set so they would fall back to standard of care that includes Interferon and Riba

[Willy50]

Hi, I'm sorry that I was not up to speed on your particulars. I just looked and it appears you just failed Sovaldi and Olysio. And you are cirrhotic.

What this means to me is that you can try either of the soon to be approved  drug treatments; either from Gilead or Abbvie.
Both should be available by late fall winter.

It is all in the rear view mirror at this point, but I do not quite understand why you did not use riba in your last TX. It is neither here nor there now, but you almost certainly have it in your future. I like the idea that your doctor was proactive enough to get you on off label Sov/Oly, but I do question why the doctor skipped riba.

We may soon see the kind of stats for cirrhotics with and without riba on the two drugs, but maybe not. Sometimes the records remain a mish mash of anecdotal. It is the actual trials which provide the kind of spreadsheets of results that are most meaningful.

I would not be in a neck break to retreat. Make sure you pick the right drug treatment best suited to your staging, genotype, subgenotype, response, il-28 genotype, etc.

I would also make sure all your levels of everything were up Vit D, all B vitamins, A, your iron is where it should be, and I would even work on tiny things like BMI or getting as fit as one can. Use every small thing you may need to get you over the final hurdle.

I would not be overly alarmed about resistance to Sovaldi, but the protease inhibitor (olysio) may result in some resistance for a spell. It seems to me that the gilead treatment took one relapser and almost immediately re-treated them, and the second go-around they cleared and SVR'ed. DO keep in mind that you may have some potential resistance issues so you may need to used everything at your disposal this next attempt.

I will repeat, I do not quite understand why your doctor did not use riba this last attempt and I do not quite agree with their statement about no difference between genotype 1A and 1-B response. Please make sure and double check the doctors recommendations against various responses on this forum before your next TX. (It costs nothing to get confirmatory opinions)

Also, do pay attention to the next Liver conference; AASLD this fall. There should be relevant information to your case,  (once again, even if it is only confirmatory. )

And am I to understand.... you are a null responder to Sovaldi/Olysio? How about other past treatments? If you have treated in the past and also been a null responder I would really question..... there would have to be a good reason that riba was skipped this past time, IMHO.

Maybe I am just walking into a discussion or circumstance I know nothing about and am missing something?

best,
Willy

[nan535]

Thank you both for your kind words.  I am happy to know you both have supportive partners to help you through this very difficult period in your lives. I can only imagine how hard it is for someone doing it alone. This is one of the reasons I post here. I see how much he needs someone to be his advocate and it makes me wonder what happens to those who don't have anyone there to support the.  So if I can be of help to someone by sharing our experience,  that's great.

I am praying one day in the not too distant future Hep C will be noted only in the history books.

Nan

[Willy50]

Some people are familiar w/ Dr. Paul Kwo. Here is an article somewhat germane to this discussion;

http://hepatitiscnewdrugs.blogspot.com/2014/05/reconsidering-whether-to-treat-genotype.html

"Therefore, in genotype 1b patients, I recommend sofosbuvir plus simeprevir, and in patients with genotype 1a, I recommend sofosbuvir plus simeprevir with ribavirin"

===================
I would suggest that your issues now in treating are your possible resistance to PI's for a period of time, your cirrhosis, your past null response, and to some degree your geno-subtype (1B or 1B; I don't know which you are), and other considerations; if you have other co-morbidities which make using riba an issue, potential for decompensation, etc.

Before considering the Gilead sovaldi ledipasvir combo I would want to see how it scores against past TX failures, past null response, with cirrhosis and for your genotype and sub-genotype.

The issue of resistance; you may have to wait up to 1-2 years..... for the resistance to PI's to revert back to wild type, but there may be more current info on this. It's the last info that I thought I understood.

If you treat in the next year, I think you will see 12 weeks with RBV minimum, regardless of whether it is Gilead or Abbvie. (I am inferring you are a G-1A)

willy

[zarmar]

Thank you for this discussion.  I am a 1a newbie to Tx, but not to HCV as I have advanced, compensated cirrhosis after 40 years with the disease.  My S/O 12 week course ends on 8/15. I am not a good candidate for RIBI given my comorbidities with lymphoma.  My concern is that my hepatologist won't know until the next week if I am SVR at EOT - I was UND at wk 8.  The 16 wk course mentioned in this post sounds like a good option for me rather than leaving S/O perhaps too early for my stage, and wait for S/L or other to be approved in a few months.  My pharmacy told me this week they are not aware of any compassionate care prescriptions being submitted for S/L at this point.  Is this a good argument for me to make to my Dr. to request a 4-wk add-on of S/O so there is not the interruption and a better shot at SVR?  I have the impression from a conversation with the pharmacist a few days ago that it is up to Dr.  Thanks all for your expertise on this.

[Willy50]

My take on it.....
there is no data on this, or very little.
I currently have a past treatment failure friend who is on Sov/Oly without riba, so I think it is common, but I question if it is wise, given that many are cirrhotics which will have increased hurdles if failure occurs.

My friend is RBV intolerant, but he has suffered through RBV before, and it would probably provide roughly the difference between treating for 12 weeks versus the added benefit of several percent of treating for 24 weeks. (just a few % points)

I guess I wonder if it would make sense to do 4 weeks of riba, then stop or continue with the riba based on a 4 week PCR and other factors, like anemia?

Even if one stopped, there would essentially be a taper as the half life decreased, and I believe it would be effective in speeding the viral reduction at a super critical time, raising the efficacy without making for serious side effects. I don't think it would seriously affect most cirrhotics, but could provide a small bump in efficacy/cure rate. It's purely speculative, and I've no clue about lymphoma issues, nor am I recommending RBV as an add on at the end of TX.

I'm just not aware of any "rule" that says all drugs must be used the exact number of days as all other drugs. We commonly see RBV dose reductions done with negligible reduction in SVR rates, so if anything, there IS data that shows this may be effective. The magic line for genotypes, past failures, cirrhotics may not yet be known; maybe 6 or 8 weeks would be better.

My point is that 4-6 weeks of riba on the front end might be as effective and WAY cheaper than adding another 4, 6, 12 weeks of DAA treatment.

willy

[Livelife777]

Willy your right.   It really is a crapshoot, and I believe the experts in the field don't have the right answers.   Your reasoning and sound advice makes perfect sense to me.  
...Kim

[zarmar]

I respond to reasoning positively, as well.  I will have a go with my Dr.  

The consulting Hepatologist I saw at Mount Sinai before Tx began and with whom I correspond with from time to time was pushing Ribi given my profile.  I don't know if  can crunch timing at this point, but if I could see her before the 8/15 ax drops on the 12 wk course, wonder if she could authorize Ribi for 4 wks?  

Thanks ever so much - I am a fish way out of my depth trying to address this new Tx world.

[Willy50]

Um no, actually I am throwing the idea out for considering adding RBV even if it is only for 4 or 6 weeks, if one is cirrhotic, a past TX failure, other negatives that may impact on SVR rates. Consider even a little instead of none at all.

If your doctor is proposing riba I would guess it is merited, and dosing can always be reduced, and so far be it from me to recommend reduction.

The original post was about sub-genotype response, and I was addressing that issue that the OP may have needed a bit more of a boost. IF the OP was a null responder to Sovaldi and Olysio it is even questionable if riba would have tipped the scales, but yes, maybe riba with 24 weeks; one may have gauged that by response rates and/or week of viral clearance

~W

[susan400]

I know that as far as in the research areas, the 1A versus 1B may have some baring on response.  I am not a scientist, and I'm really not that great at keeping all the science of Hep C straight in my head.  Usually, when somebody starts discussing the chemistry aspects of the Hep C virus, I start getting brain fog and feel like my head is spinning and really can't make any sense of it.  But, I have treated more times than anybody else I know of.  I'm sincerely hoping that this treatment is it for me & that I SVR.  I get my 2nd viral load (week 8) on Aug. 13.  I met with my doctor last week and we were having the discussion.  Hoping that this is it for me, but the 'what if' conversation.  If for some reason, I fail to clear the important hurdle of undetected through this treatment and on the end of treatment check as well and I relapse...   I have told him and he supports my decision, that I will not turn around and jump right into the Ledi/Soval combo.  Or even the Abbie one that's coming up soon.  I will wait about 3 yrs again.  Right not with as much as I've treated, my body can only take so much.  My doctor does say though, that even though I've never SVR'd, YET, that all of these treatments have helped to temporarily suppress the virus and give my liver a chance to rest.  I've had this for 30 yrs and actually have very little damage.  I don't do any major dietary restrictions, but I do work out about 5-6 days (even have been known to do 21 days in a row) a week.  I do weights like every other day with a day off in between and the other days I do cardio equipment, i.e. treadmill, elliptical, stationary bike.  I pretty much eat whatever I want, except try to avoid fried foods and spicy foods(only because spicy foods kill my gut).  I haven't drank alcohol, or smoked cigarettes for 19 years.  All these things, my doctor says have helped to keep my damage level under control.  Also, I've never had a weight problem and haven't done the yo-yo gain/loose weight thing.  I pretty much have stayed within the same 5 lbs for the past 20 years.  I might go up 5, but then, a month last be back down the same 5.  Never losing like something crazy like 40+ lbs. or like gaining 50+ lbs., nothing extreme like that.  My blood sugars have also, never turned diabetic.  Other than the fact that my immune system obviously s*cks, because otherwise, seems to me, I would have SVR'd by now.  But, at least this time, I have that hope since I finally heard undetected back on week 4 blood draw.   Susan400

[hepcandme]

Here's my basic info:

Diagnosed with Hep C in 1992
May have been infected as early as 1974 through blood transfusion but, hard to say?

Genotype 1B (I had thought 1A for a long time)

Cirrhotic - low level edema and ascites, portal hypertension

MELD score 12 in October 2013
Reduced to 10, then 9 and held steady at 8 since last April

Treated off label with Sovaldi/Olysio from April -June
Relapsed at 4 weeks EOT

MELD score now 10
ALT levels doubled (but still not Terrible - 47)
Viral load at close to one million at 4 weeks EOT
Other labs in normal or close to normal range - platelets a bit low

First time treated and now can say I am a null responder  :(

My understanding is that one does not build up a tolerance for Sovaldi but that Olysio is out of the picture for me now

I am very anxious to try again because I just don't feel well - what I call The Uber Fatigue and aches. I wish that I could work out 4 times a week but really have a hard time getting out of bed, insomnia, headaches, constant pain caused by related neuropathy. I just feel pretty awful most of the time and dream of a time when my energy level was more than a lizard sunning on a rock

I am trying to be patient for the new "miracle" drugs but I was treated off label probably because my circumstances were "interesting" to researchers

Cirrhotic, naive treatment patient with fairly good lab numbers

Serious, I would have stayed on the S/O for 24 weeks if that was on offer but I agree with a precious poster that sometimes it feels like a crap shoot - how long to treat, what combo, add Riba or not, what will insurance co agree to fund?

And I have read that people on Riba had some really awful side effects so I don't really want to take it and my reading of the latest trials show no additional benefits

But I don't want to be a baby about this and will take the Riba

But no to Interferon, thank you

[Willy50]

are you sure you are a null responder?
==========
http://www.medscape.com/viewarticle/713174_2

Definition of Relapse and Nonresponse
Relapse and nonresponse are defined on the basis of the virological response to treatment (Fig. 1). A patient is said to have experienced a virological relapse if HCV RNA decreases and remains below the limit of detection (<50 IU/mL) during treatment but becomes detectable after cessation of treatment. If HCV RNA rebounds and becomes detectable in such a patient before treatment is completed, this is referred to as virological breakthrough. Virological nonresponse is evident when the serum HCV RNA level remains above the limit of detection throughout treatment and is formally defined as less than 2 log10 decline in HCV RNA between baseline and week ...............................................................................12. A patient who has less than 1 log10 reduction in serum HCV RNA at week 12 of treatment is said to have had a null response.....................

(my emphasis-~W)
===============

So...like I say...I am in the dark here, but if you relapsed by week 4 EOT, I'm guessing that you cleared earlier at one point. I'm also guessing you had a viral load drop greater than a one log drop.
Therefore, I'm guessing you are NOT a null responder.

Can you list your starting VL, any PCR data along the way?
I would guess you are a responder.
I would guess that a longer duration may have worked,
or that adding riba may have taken you over the hump.
I'm also guessing that either new treatment may work for you (whether Gilead or Abbvie) but that you may need to do riba to make sure things work this time.

This is not the ONLY way, but it is *one* way.
=========

I understand your reticence. I have been there myself.
I treated last year and ended up with some neuropathy myself; the possible result of anemia. (possibly compounded by riba induced anemia)

If you have a MELD score I assume you are being well cared for. When was your B-vitamins checked last? Magnesium? Deficiencies here could make your neuropathy worse. How about any diabetes issues? (can contribute to neuropathy). Review any drugs you may also be taking and check against any sides you are having, ; some lower B-vitamins, for instance, making neuropathy worse.
===========

It looks to me as though you may need to recover, check a few things and you could probably retreat in a year and have a 95% chance of SVRing; thereabouts, based on the Abbvie trial results.

I'm basing that on you waiting to recover, a few possible possible tweaks that could improve outcomes (bolster any deficiencies; Vit B, D, A magnesium, improve insulin issues, if any).

Abbvie has a great treatment which is more effective on 1-B's than 1A's, but your issue now is possible resistance to a PI; ABT-450 (part of the abbvie regimen) a protease inhibitor, so you would have to wait for that resistance to diminish.

I believe you could treat with Gilead's Sovaldi, Ledipasvir (NS5A inhibitor), and RBV as soon as it is approved; this fall.

As mentioned, the fall AASLD will have some data and may also have some presentations for people whom like yourself need treatment advice on where to go from here.

Willy

[hepcandme]

Everyone on the new regimens becomes "undetected"

Viral Load was about 7 million at start of treatment
57 at 3 weeks
undetected at 8 weeks and 12 weeks

then, relapsed when tested 4 weeks after EOT

So, maybe I am using the term null responder incorrectly or they need to reconsider the term since everyone will be undetected during treatment?

I have a MELD score because I needed to be "listed" in order to begin treatment that most likely would include Interferon and there is a danger (slight) that Interferon can actually cause decompensation for cirrhotics

I am not taking many meds now - Spiro 25 mg (diuretic), Vitamin B 500 mg and a once a week antibiotic - Cipro

I calculate my MELD score every time I get lab results using this calculator:
http://optn.transplant.hrsa.gov/resources/MeldPeldCalculator.asp?index=98

But honestly, I can calculate it now in my head as soon as I get the numbers

I know that I should be patient but I feel like I am getting more ill, certainly more anxious about my prognosis

I will certainly pay attention to the data coming out the conference and I Really hope that I can start the new treatment soon. For those who have gone through many, many attempts to conquer this disease, I am in awe of your courage and resiliency

I need a treatment option with a start and finish day in my future that I can hang my hope on