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GT3 started harvoni/riba questions

Hi
I've followed along with this great forum on and off for many years and have been very grateful for the fantastic info shared here by the wonderful level headed forum members that keep things on track with good knowledge and always being on top of trial results and ability to interpret them in terms of our own real life situations.  So thank you!

As I state in the title, I have GT3, a starting viral load of 30 mil, stage 2 grade 1 liver biopsy three years ago, ultrasound shows normal size but fatty, fibrosis blood test was negative.  I really would have preferred to wait for the newer treatments for my genotype that are hopefully coming out in a year or two, daclatasvir and other new one by Gilead, but I have been suffering with worse and worse fatigue and my autoimmune conditions seem to be growing by the month.  So far I have been diagnosed with cryoglobulinemia, aquired angioedema type II, and myasthenia gravis.  I have been bedridden for the past couple of years, and with my nerve pain now uncontrollable, I felt it couldn't wait to treat the HCV any longer, as it is considered the primary reason for the cryo and hence the nerve damage.  I have taken 'chemo' treatments to help in the meantime (rituximab) with lessening results.

Due to being so sick, I didn't feel I could manage six months of riba to do the SOC for my GT (six months sov/riba), so my hepatologist and I pushed for harvoni and riba for 12 weeks.  My starting hemoglobin level is 12, but I had very low ferritin levels and high RDW.  I am not sure if the kind of anemia that the low ferritin and high RDW shows (it pertains to low stores of iron in the bone marrow I believe) is the same kind of anemia as you get from ribavirin (hemolytic), so I'm not sure how at risk I am for getting anemia early on.  I am 115 pounds, and started at 1000mgs riba.  Treatment started this past Friday 13th.  I understand that taking an iron supplement is of no use?  I was taking one that is derived from natural food sources.

I know there was just one small trial, and it was not recommended that harvoni be used for GT3 because it hasn't been tried in enough people yet, and I wonder if anyone can shed any more light on reasons why it perhaps wasn't studied further, or recommended besides the small number of people in the group?  I remember reading that ledispavir was not actually effective in vitro on GT3 even though it did seem to have good results in the small study.  I'm just wondering if I have made the best choice for myself.

Another question, (and I apologize this is so long!) is more for any possible pharmacist types in the group.  I take a medicine for chronic daily migraine related to my conditions and a small tumor in my brain called Fioricet which contains a drug called butalbital.  Seeing that phenobarbital was contraindicated with harvoni set alarm bells off, because I knew that the drugs are chemically similar (cousins if you will), butalbital being a much shorter acting 'version' of the phenobarbital.  I called Gilead that said they couldn't comment because they hadn't tested the drug, but to speak to a pharmacist.  Called the pharmacist, he was confused thinking the reaction was the other way around, but eventually said that it would likely have a weak impact on blocking Harvoni just as I imagined.  Of course I want to avoid that!  However I suffer terribly with my migraines and after years, this is the only drug that helps.  For the first 3 days until I worked out the interaction I took minimal doses of the Fioricet.  Does anyone have any knowledge about this?

I really appreciate anyone getting through that long first post!
19 Responses
Avatar universal
http://regist2.virology-education.com/2013/14hivpk/docs/30_Mathias.pdf

jules
Avatar universal
http://www.medhelp.org/posts/Hepatitis-C/Harvoni-with-her-type-3a/show/2403891#post_11666948

http://depts.washington.edu/hepstudy/presentations/uploads/129/electron2__ledipasvir_sofosbuvir.pdf

Here is an older post from Jan 2015 and some information which may help.  Sounds like you have your hands full.  I am sure others will chime in to help out.  Hang in there!

Jules


Avatar universal
Sorry, I have no experience with those meds and their interactions.  I just wanted to say 'Hi' and welcome to the Forum.  Also a Gt3, presently in waiting mode - EOT12 Labs next week.  As you probably know, from watching, many here are extremely knowledgeable in different areas of tx, etc.

I expect someone will know something to help you get the answer your are seeking.  

Good treating!  Good health! And get that Dragon!

Pat



Avatar universal
Thanks Pat and Jules.
I really appreciate the link to the other person using harvoni for gt3. I hadn't been able to find that anywhere.  JimmyMose hit the nail on the head when he outlined reasons for approval for the offlabel treatment - it was indeed the price difference that my doctor used to garner the approval from insurance, and I can tell you they leapt at the chance.  

As I said, I just dont feel I can handle 6 months of riba, and I really don't want to put my body through more than I have to, especially being as sick as I am, but it feels like such a gamble too.  I feel like 12 weeks is 'doable', so thought I'd take that route if there was a good possibility ofm to being as effective as SOC.  The only thing I didn't understand is the EC50 comment, and how that plays into the effectiveness of treatment on GT3.  In the very least, perhaps my liver will get a break, and by the time I am finished, or soon thereafter, daklinza will be approved.  I hear it is an easy treatment with minimal sides.  So long as treating with sovaldi doesn't mean a second try gives reduced chances.  Perhaps of JimmyMose is around and reads this he can explain EC50 to me.  It might be to do with ledispavirs limited activity on GT3.

Pat, I guess you coped ok as far as anemia?  Congratulations for finishing treatment.  Boy, what a wait that must feel like!
Avatar universal
Biological Activity of Ledipasvir

Biological Activity of Ledipasvir



Ledipasvir(GS5885) is an inhibitor of the hepatitis C virus  NS5A protein.  Ledipasvir is an experimental drug for the treatment of hepatitis C.
IC50 Value: 141 nM (EC50, JFH1/3a-NS5A hybrid replicon) [1]
Target: HCV NS5A
in vitro:  Against JFH1/3a-NS5A, DCV was more potent (EC(50) = 0.52 nM) than GS-5885 (EC(50) = 141 nM). DCV sensitivity was increased against JFH1/3a-NS5A-M28V (EC50 = 0.006 nM), A30V (EC(50) = 0.012 nM), and E92A (EC(50) = 0.004 nM) while the NS5A-A30K and -Y93H variants exhibited reduced sensitivity to DCV (EC50 values of 23 nM and 1120 nM, respectively) and to GS-5885 (EC50 values of 1770 nM and 4300 nM, respectively) [1].
in vivo: GS-5885 was well tolerated and resulted in median maximal reductions in HCV RNA ranging from 2.3 log(10) IU/ml (1 mg QD) to 3.3 log(10) IU/ml (10 mg QD in genotype 1b and 30 mg QD). E(max) modeling indicated GS-5885 30 mg was associated with>95% of maximal antiviral response to HCV genotype 1a. HCV RNA reductions were generally more sustained among patients with genotype 1b vs. 1a. Three of 60 patients had a reduced response and harbored NS5A-resistant virus at baseline. NS5A sequencing identified residues 30 and 31 in genotype 1a, and 93 in genotype 1b as the predominant sites of mutation following GS-5885 dosing. Plasma pharmacokinetics was consistent with QD dosing [2].
Toxicity:
Clinical trial: Combination Therapy for Chronic Hepatitis C Infection. Phase 2

http://www.medchemexpress.com/Ledipasvir.html

jules
Avatar universal
I wish I could have waited for 5816 or daklinza, and indeed that was my goal, but I was just getting too sick with cryoglobulinemia to wait.  I'm quite unclear about how likely I am to reach a cure on this treatment, but I hope my odds are good, because three months of riba for me is still going to be quite rough given how fatigued I am already, and my starting hemoglobin levels.  I am not strictly anemic yet - well not with hemolytic anemia, I certainly have low iron stores.

I should probably have different threads for different questions, but I wondered if anyone had a clue if it was safe for me to take an iron supplement - I do know this won't prevent hemolytic anemia.  The supplement is a megafood supplement called 'blood builder'. It is made from concentrated food sources.  I thought it would at least be helpful for my pre existing low iron levels shown by my low iron and high RDW tests.  
Avatar universal
Yup.  I did the 24 weeks Sol/Riba.  



Just didn't do anything, ate very ' liver friendly'.  My husband made me salads, brocolli, cauliflower, carrots, - veggies he does not like - found lots of different ways to cook chicken, fish, etc., and rested some more.  Bless him, not only did he prepare things like that to help my liver, he ate them with me!  I felt so loved!  Also, he sought out sites on facebook and youtube with cute or interesting animal things, funny things, etc to get me laughing - all of which kept my spirits up and that, was the best dose of medicine of all!

Also, for church, doctor visits, etc., used a walker, so if I had to sit down immediately, I could -- and to steady me so I didn't fall when I was so week.

Oh, speaking of laughing, we probably haven't mentioned the extra emotionality some (many?) of us experienced from the Sovaldi.  I was warned by others on this Forum, so prepared in advance.  I didn't watch sad or tear jerker movies, or tv shows, was careful what I read, didn't watch the news.  A good thing all round.  An example of what I'm talking about, is I was reading the Sunday School lesson aloud to my husband on the way to Sunday School (our usual practice so it was fresh in our minds) 3 or 4 weeks into tx.  This lesson had a paragraph long very poignant example.  By the second sentence out od 4 or 5, tears were rolling down my cheeks.  Now just weeks before that would not have happened.  That kind of thing stayed with me up through end of tx and for approximately a month after.  Pretty much back to normal now.

Sorry this is so long, but hope the info helps.  Most certainly it is doable.  Women have more problems than men with the anemia thing, unless ther are other medical problems, which sounds like your case, but, as I said, it it definitely doable, especially if you are aware, and y'all watch your HMG, you'll do fine!

Pat
Avatar universal
I wouldn't recommend any iron supplements because of your liver but has your Dr suggested the possibility of Procrit shots to raise your Hgb levels?  Several people on the forum have used them to increase their levels with great success.  You might want to talk to him about it.

Jules
Avatar universal
Oh, and I forgot Riba Rage - that did not happen to everyone.  I did have two episodes, but knew about them and was able to apologize to the people I yelled at, and explain.  

After the 1st one, I watched out, and usually became aware andgot myself off by myself, which worked.  We had a 'code' if my husband saw me getting agitated and saw that I hadn't noticed, he would ask me if it wasn't time for a nap? Worked very well. As I said, though, not everyone had this problem.

: -).    Pat
Avatar universal
Hi trigger..
Best of luck.. You've started now.. So best to try to be positive.. In trials.. It did pretty well for geno 3.
Lediprasvir is supposed to double the effect of sofosbuvir.. Making it stronger.. So that's good.. And one reason why its 12 weeks not 24.
And you get the other DAA !
So lots to be positive about,.. Just try to keep upbeat .. It's only 12 weeks tell yourself.. You can do it!!!!
You cope with so much already!!!

Wishing you all the best!!
Alico
Avatar universal
Hi above comment was to trigger..
Now this one for patra..
Hey pat.. Just a Q ..
Did you svr???
And what was your fibroscan score pre tx!!!

Thanks..
I'm geno 3 treatment experienced rib and interferon.. Fail.
Waiting to retreat...
Just wondering like trigger best combos...
And if the 24 week has good odds?
Avatar universal
Patra, I very much appreciate you taking the time to share with me all that excellent stuff that helped you get through treatment.  Really good advice in there!

I don't believe that iron is necessarily the problem originally thought for those that are not cirrhotic or too badly damaged.  Definitely not a good idea if your iron levels are high, and this can certainly happen with HCV and liver damage/cirrhosis (which is where the advice to avoid iron comes from aI believe), but I have the opposite issue, possibly due to autoimmune problems, or dietary insufficiency - although this makes no sense to me.  I was more asking this question on an interaction with harvoni basis.  As it is a food based supplement I think it is probably safe, as all info supports no food interaction with Harvoni, but of course I want to minimize my risks.  

I will be bringing up procrit certainly if my labs have dropped at the two week point.  

Alico,  thanks for,the encouragement to,be positive and avoid the what ifs for now.  I'm committed, and time to just go,for,it and hope for the best!  I can't hear these reminders enough.  Cheers.
Avatar universal
I was 813,096 pre tx, that test was done last may.  

I treated in 94/95 w/ Interferon injections 3 x week for 7 mo.  Null Responder, I think, but could have been relapser.  I didn't know enough in those days to find out, or that the info mattered.

I am still waiting for my EOT12 Labs - next Wednesday, 1 wk feom today.  Won't get the results positive or negative, until Dr visit 3-11.

That was the b est available last yr for Gt 3 and Dr felt since i was Fibrosis
F-3. Level A0 - A1, I really needed to start tx to stop the virus, at least for those few months, so the Fibrosis wouldn't progress to Cirrhosis.  I Agree.

I was hoping that Daklinza would be FDA approved by now so that I could be treated with Dac/Sol as THAT seems to be the best going for Gt3s.  Praying I won't need that, but like to plan ahead.

I feel well, if that is anything to go by, but I don't know.

Oh, yes, Fibroscan: Dr was going to order one, but reviewed my chart and saw that I had had a Biopsy 1-31-14, when I had gall bladder surgery, so I didn't need one.  Don't know what will happen after tx, but he mentioned something about testing @ either 6 month post tx, or 1 yr.  (I still have no short term memory thanks to the INF - oh well, I just deal with it) : -)

Thanks for asking.  I will post after I get my results, either way.

Pat
Avatar universal
Go for it!  I am not sure that I   would take even vegetable Vitamin B supplement on tx, but CALL GILEAD.  They have a nurse available to take calls.  They should be able to help with that.  

Also, your Specialty Pharmacy Pharmacist should have information.  
I would certainly check with those two before doing anything that might slow down or affect the efficacy of the Harvoni - or whatever meds, for that matter.

It looks on you site, like you asked a question (maybe on another thread) about flossing.  That is the recommendation.  it seems to be even more effective to do that then the water pic, than either one separately, per my Dentist, but since my gums are so sensitive, I do not floss anymore.  I may pay for that in future, but no matter how many times I flossed, my gums didn't 'toughen up' and I got tired of bleeding gums!  

Do get Biotene, or somesuch mouth rinse, mouth spray, and even tooth paste.  It did seem to help with the Dry Mouth problems from tx.  On the other hand, I have not seen that issue listed by anyone treating with Harvoni, so thT may not be an issue there.

Keep on keeping on.  You Can Do this!  (big smiles, here).

Pat
Avatar universal
Yes, I could always call Gilead, but if they haven't listed it as having a reaction as per an earlier discussion with them they will tell me they can't advise as it hasn't been tested.  Pharmacist may be of more help, but common sense does seem to reign supreme.  My last call to them confirmed that I seemed to know more than the pharmacist!  He had to do,an online search of info I already knew.  I also think the less you take the better as it's just less risk even if minimal.

Sorry to hear about your poor tender gums!  At least you can use the waterpik then.  They are very good, and definitely less traumatic for the gums.  I have some biotene as I do get dryness.  I haven't tried it yet.  I'll give it a go!
Avatar universal
Trigger just wanted to say that I wish you well with treatment.  Actually the 12 weeks seem to fly by, and before you know it your done.
My best
.....Kim
Avatar universal
"he can explain EC50 to me" sorry that is too technical for me to understand.

I found this trial with completion date March 2015 results due June.
New Zealand location
Sofosbuvir  Regimens for the Treatment of Chronic HCV Infection in Subjects With Chronic Genotype 1, 2, 3, or 6 HCV Infection
https://clinicaltrials.gov/show/NCT01826981

Hopefully the Harvoni plus RBV for GT3 results will be just as good.

Best wishes for achiving SVR
Avatar universal
Thanks JimmyMose and LiveLife.  Well, I guess I'm doing this thing.  Hopefully it all turns out well!  
Avatar universal
By the way, I did look up EC50, and it seems to be one of the mechanisms or pathways that ledispavir is absorbed in the body by.  it appears that it IS effective on GT3, in vitro, but just hasn't had trials on it, perhaps because they have another drug in the works (GS8516) that is effective across ALL genotypes, which they will be rolling out soon.
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