My thoughts on Harvoni dosing, 8, 12, 24

[Bob V]

JoeK9999 post:
One thing I want to note here. When I spoke to Gilead months ago, they made it clear that "our" doctors would make the decision of 8 , 12 or 24 weeks based on our individual criteria. They stated it was not a test while on treatment based criteria like
past protocols were where they lengthened times if the test results were not what they liked. In other words if you are scheduled for 'x' weeks, that's what you will get and finish, then you will have to wait 12 weeks post treatment for your outcome. We may not like that approach, but that comes straight out of Gilead's mouth.

We could get a test everyday and it could be different. The proof is with Lucinda on the trials. At 4 weeks undetected, at 6 weeks detected and at 12 weeks post treatment undetected. I can still feel the effects of the meds in my system 2 weeks after EOT. I don't know if they were still active or they just wacked my body.

I have no idea what my 12 weeks post test will be and yes I have anxiety about it,
as we all do, but all I we do is wait and see. At EOT it is out of our hands.
All we know right now is the results of the clinical trials of 2000 people.
In the worst case scenario, we all know there are great strides going on right now in research for other cure protocols that will be hitting the market soon.
------------

As a nurse I don't understand the thinking that a doc can't adjust doses based on labs. I get the insurance issue but to say you started on 8, 12, 24 and you can't change just seems like bad medicine to me. If I was starting now I would tell my doc to ask for 24wks (not sure if insurance would ok it but I would try) and we could adjust from there. Looking at the drug info I believe Harvoni is 99% at 24wks, I just feel the option should be available.
BTW my doc and I make co decisions on treatment, if he wasn't ok with this I would find a doc that would. It was me that told him I wanted Harvoni not S&O. I gave him my reasons and he said ok let's go with Harvoni.

[bridget]

I hope eventually the cost of Harvoni will drop enough that everyone can be approved for 24 weeks & treatment length can be based on response during treatment.

[donk]

Quote from http://www.hepatitisc.uw.edu/page/treatment/drugs/ledipasvir-sofosbuvir "a treatment duration of 8 weeks can be considered in treatment-naive patients without cirrhosis who have a baseline HCV RNA level less than 6 million IU/mL."

I think basing treatment duration on viral load is flawed. Viral load fluctuates. If under 6 mil at the time of testing when you take the first Harvoni pill it may be 1-2 months later and the VL could be above 6 mil. I was under 6 mil and was told by the hep c nurse I would of been prescribed for 8 weeks but I relapsed in INF/RIB in 2002 so they gave me 12 weeks (no cirrhosis). I've been above 6 mil in VL tests since 2002 when I first did tx.

[dragonslayer]

>>As a nurse I don't understand the thinking that a doc can't adjust doses based on labs. <<

Bob, I think it probably has something to do with the fact that its not part of the protocol... No trial results Im aware of show results with a mid course correction such as this, even though it makes eminent sense, Im sure, to most of us here.  Doctors, generally, will not 'punt' like this until there is something showing results.  Im guessing, later on, when they have more to go on, this might become standard, but I can see why many wont do it now.

[Bob V]

Paul
They know what % of people that were not UND at week 4 and went on to fail tx, etc.
The info it there but that's why I say the doc should have the option to an adjust  dosing.

[dragonslayer]

Bob, yea, I tried to pry that info out of the Gilead pharmacist I talked to, as well as how many low detectables went on to clear it.. That kind of info, he said. Was available to the doctors, but not to us plebians.  He said it was heavily FDA regulated, etc, etc...

Also, I think the fact that theyre using <25 has a LLOQ point throws a bit of a monkey wrench in how to interpret the data.

[Bob V]

Yes Paul that's what got me thinking about this.

[dragonslayer]

Yes Paul that's what got me thinking about this.

Right.. I think it was specifically this which I think really widens the goalposts:

"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."

[Bob V]

Also, I think the fact that theyre using <25 has a LLOQ point throws a bit of a monkey wrench in how to interpret the data
------
Not sure I understand this. I'm going to call Gilead if my 8Wk results come back detected and ask LOTS of questions.

[dragonslayer]

Make sure you call Gilead Medical Info and not Supportpath!  And try and speak with a pharmacist or higher.

[Bob V]

Yes Paul I go right to the RN or Pharmacist.

[Bob V]

Funny my doc office just called and said CVS wanted Dr approval for another 28 doses. I told them I was on bottle 3 now but if they get approval of another 28 doses I'll take it.

[Katie]

I certainly agree with both of you guys.  My example is under 3 million VL, no cirrhosis, no prior treatment and my doctor and insurance approved a 12 week treatment.  An 8 week treatment wasn't even mentioned to me.  I am very happy to have this and find it interesting how it varies from doctor to doctor.  Also I started December 4th so it wasn't right at the beginning of availability for HARVONI.   

I had been following the updates on S/O and also on Harvoni and when I went in to discuss it with my doctor, I brought in my folder with the info and told him that is what I wanted.  He had had success with S/O + Riba and tried to get me on that months before but I chose to wait.  He is my GP but is also an internist and has been dealing with many Hep C patients over the years and saw many failures on the old treatments for 1a.  We are so lucky to have him here on this island in SSE Alaska.  Very competent and compassionate.

It will be really interesting to see how the results stack up once the first quarter's results are in for Harvoni.  Hopefully their expectations are correct and we will get on with our lives as healthy, well informed patients who can become advocates for those still waiting or unknowing what is available.  Many health care workers aren't even aware of this new breakthrough, which I find amazing.

Katie

[JoeK9999]

JoeK9999 post:
One thing I want to note here. When I spoke to Gilead months ago, they made it clear that "our" doctors would make the decision of 8 , 12 or 24 weeks based on our individual criteria. They stated it was not a test while on treatment based criteria like
past protocols were where they lengthened times if the test results were not what they liked. In other words if you are scheduled for 'x' weeks, that's what you will get and finish, then you will have to wait 12 weeks post treatment for your outcome. We may not like that approach, but that comes straight out of Gilead's mouth.

We could get a test everyday and it could be different. The proof is with Lucinda on the trials. At 4 weeks undetected, at 6 weeks detected and at 12 weeks post treatment undetected. I can still feel the effects of the meds in my system 2 weeks after EOT. I don't know if they were still active or they just wacked my body.

I have no idea what my 12 weeks post test will be and yes I have anxiety about it,
as we all do, but all I we do is wait and see. At EOT it is out of our hands.
All we know right now is the results of the clinical trials of 2000 people.
In the worst case scenario, we all know there are great strides going on right now in research for other cure protocols that will be hitting the market soon.
------------

As a nurse I don't understand the thinking that a doc can't adjust doses based on labs. I get the insurance issue but to say you started on 8, 12, 24 and you can't change just seems like bad medicine to me. If I was starting now I would tell my doc to ask for 24wks (not sure if insurance would ok it but I would try) and we could adjust from there. Looking at the drug info I believe Harvoni is 99% at 24wks, I just feel the option should be available.
BTW my doc and I make co decisions on treatment, if he wasn't ok with this I would find a doc that would. It was me that told him I wanted Harvoni not S&O. I gave him my reasons and he said ok let's go with Harvoni.

Bob - I totally agree with you. I was just stating what Gilead told me. My doctor was swaying between 8 and 12 weeks while on treatment. Because he saw detected at 4 weeks I think that is what changed and he gave me the 12 weeks. I had to insist for the 4 week test as he was positive I would be UND at 4 weeks.He was wrong and I am glad I was proactive. His view was no tests until 6 months after EOT which I don't understand because he has treated hundreds if not thousands over the years.
After this experience, my advice to anyone else is to interview your doctor before you start treatment and make sure he is in synch with what you expect. It's our life.
Anyway I finished 12 weeks of Harvoni over 1 month ago and am doing a test at the 12 week mark to see if this did the trick. Before treatment I was at VL 3.7 million, stage 0-1, treatment naive which can very well be an 8 week candidate. I like the odds on 12 weeks vs 8 weeks even if it is a few percentage points.

[Bob V]

Joe
I had a long talk with the pharmacist at Gilead and the bottom line was 8, 12, 24. I pointed out the ION 2 study had 99% SVR rate but she said the ION3 group was done as 8, 12, 24 with current guide lines. That's what the FDA approved so that's the protocol now.

I'm sure as the real world numbers come in they will reevaluate this.

[dragonslayer]

Joe
I had a long talk with the pharmacist at Gilead and the bottom line was 8, 12, 24. I pointed out the ION 2 study had 99% SVR rate but she said the ION3 group was done as 8, 12, 24 with current guide lines. That's what the FDA approved so that's the protocol now.

I'm sure as the real world numbers come in they will reevaluate this.

They'll have to.. Im sure I cant be the only one out here in the real world who was prescribed 8 wk treatment, and who isnt undetectable at the end of it!  The real question they'll have to determine is, is there any difference in the number of real world failures for the 8 wk group vs the 12 wk group.  In the trials, it was negligible.  Lets see what happens out here..  Also will have to be determined if those who qualify for the 8 wk treatment and given the 12 do better than those given the 8 wk. 

[Katie]

Hi Paul,  I am curious when you go in for another VL test.  There have been those who were detected at EOT and then later found they were cleared.  With such a low detection, that could very well be you.

We are all rooting for you and I appreciate you being on this forum and sharing so much.  I have 10 more pills to take and was VL 59 at 4 weeks.  Haven't been tested since so my fingers are crossed, but you have kept me grounded.  I did receive 12 weeks, but I think there is still a lot to learn in the real world scenarios.

Take care and enjoy your day!

Katie

[katelovesyou]

I have just finished 3 months of harvoni , viral load undetectable after first 6 weeks.I experienced a rush of unfamiliar feelings , all the way from feeling my teeth and gums were being attacked to fluish symptoms. I now understand this is the virus die-off which is very real and creates symptoms of it's own.
At 6 weeks test no virus detected.(b ut reading this blog I see the viral load can return! )

I am now finished with 12 weeks of HARVONI.. the only side effects is alot of joint pain ...working with diet to eliminate that .

My next virus test is in a few days hoping for no viral load.

[dragonslayer]

Hi Paul,  I am curious when you go in for another VL test.  There have been those who were detected at EOT and then later found they were cleared.  With such a low detection, that could very well be you.

We are all rooting for you and I appreciate you being on this forum and sharing so much.  I have 10 more pills to take and was VL 59 at 4 weeks.  Haven't been tested since so my fingers are crossed, but you have kept me grounded.  I did receive 12 weeks, but I think there is still a lot to learn in the real world scenarios.

Take care and enjoy your day!

Katie

Hi Katie, Im scheduled for my 12 wk follow up appt on April 20; I'll get the blood drawn  a week before.  Listen, I didnt realize you could be detected at EOT and still clear ; Does this really happen??  UND seems to be the holy grail, so with my count of 29 at EOT, I assumed it was a failure.  Various people told me it might not be a failure and not to judge til I get the 12 wk post treatment result.. I figured they were just being supportive and conciliatory, but maybe I was too quick to judge..   Im trying not to get my hopes up, so Im fully expecting the result to be less than desirable, but in the back of my mind, much as I try and erase it, is the thought that maybe, just maybe, SVR12 will be the result.. I really try not to give that one much space in my head.  The disappointment when opening the lab result from my EOT test was staggering.. I mean, given the SVR odds of 95%, I didnt think there was any chance Id be detectable, especially with a trials on-treatment failure rate of Zero  (its hard to know if my eot result would have been judged an on treatment failure or not, and I guess that will only be known at the 12 wk post treatment marker)..  At any rate, Katie, I thank you much for reinforcing this idea, and Ill just pack it away with little fanfare, unless it deserves to be brought out in all its glory at the next test..  But really, Im not expecting much... T'will be much easier to deal with that way.

Katie, I really appreciate your comments.. Besides, 'Katie' was the name of my first wife, so, perhaps, Im a little partial   Im so hoping you achieve UND soon, at the end of your treatment.   Were you eligible for the 8 wk treatment, but got 12 anyway?  When is your next test.. after you finish the 10 pills left I presume.. Im looking forward to seeing your results... You know some people like to have lots of blood tests and some doctors comply; others, like mine, tend to believe since the only test which means anything to them is the 12 wk post treatment test, thats the only one they do.  I had to call the office specially, and speak to a nurse there, in order to get the order for even an EOT test.   To me, the anxiety of awaiting multiple  test results is worse than not knowing at all.. And, since the only result which counts is the 12 wk test, Im really fine not going for the intermediary tests. 

Best wishes again for a great result in a couple of weeks!

[Bob V]

Kate
Congrats on near finishing just because you're undetcted at end of treatment or close to that time doesn't mean you're virus free. That's why we get tested at 12 or 24 weeks post treatment, it gives the virus, if is still present, a chance to multiply and be detected.

[Katie]

Thanks Paul, and yes I did read that somewhere.  I've read so much I am not sure where.  I figure the Harvoni is still working for awhile even after the last pill AND your immune system is working better than it has in years.  Perhaps those little alien buggers left over are damaged enough where they can no longer replicate (that is purely my thoughts) so I think we just have to wait it out and see what happens.

I am on 12 weeks, but with my history, if I had a different doctor, I would have probably been given the 8 week treatment.  I am grateful my doctor fought for the 12 weeks.

I am scheduled to have a blood test after the 25th and then again 12 weeks later, and that will be the most difficult for me.  Once I realized that UD, really doesn't mean you are clear but relates to the sensitivity of the test and that you need to wait a period of time to see if there was still a small number able to kick in and replicate, I don't think any of us will be certain of being virus free until the 12 weeks after treatment.  I have to keep that in mind so I don't lose sight of reality.  Your scenario just confirmed those feelings.

You are always on my mind.

Katie

[Katie]

Kate
Congrats on near finishing just because you're undetected at end of treatment or close to that time doesn't mean you're virus free. That's why we get tested at 12 or 24 weeks post treatment, it gives the virus, if is still present, a chance to multiply and be detected.

Hi Bob, I did realize that however I did read where someone's VL at EOT was very low and they cleared at 12 weeks.  I think in the next several months we will have a lot more information on the percent cured and the time frames required.

Hope all is going well for you!

Katie

[lovinglife]

SO you guys seem to know what you are talking about. I need your advice.  I was 6mill VL (for years) and no cirrhosis.  I got approved for a total of 12 weeks Harvoni by BC, but I suppose I have the option of stopping at 8 weeks if my numbers are good.  I'm barely a month out in tx and no blood work yet.  I was hoping to do 8 weeks bc of my kidneys.  I don't want to sound like a worrywart (which this illness can make one be), but I do worry about this.  Had a bad kidney infection in my youth and have also had (mainly controlled) hypertension for years, which is also hard on the kidneys, as are many meds of any kind. I also had exposure to  a dialysis unit and learned that our poor kidneys can only take so much! (dialysis is hell). And lots of folks in their senior years end up on dialysis from renal failure.  Bottom line, I am trying to cut back on meds taken.  Is this a stupid thing to do or should I "accept" the full 12 weeks tx even if the numbers are still good, and forget about the kidney issue?  I am in my later 50's. Thanks much and I will reread this thread tomorrow when I am not so tired.

[Katie]

Hi Loving Life (me too)    Your worry about kidneys is something to discuss with your doctor, however if the doctor says it's OK, I would definitely go with the 12 weeks.  Harvoni medication was developed to get to the liver and go after the virus and because of this results in minimal side effects.  Some experience more than others and I am sure it relates to overall health, so I suggest you look into it and you may even want to call Giliead :
http://www.gilead.com/responsibility/us-patient-access/support%20path%20for%20sovaldi%20and%20harvoni

Congratulations on beginning your treatment and I know you'll find this forum beneficial.  It is good to have others to communicate with that are on the same journey.  It can be a lonesome, misunderstood trip.

You aren't alone!

Katie

[Katie]

Bob, I just realized you were talking to Kate, not me.  Gets confusing as there are a lot of "Kates" on here. 

[Bituman]

Hi Katie, Im scheduled for my 12 wk follow up appt on April 20; I'll get the blood drawn  a week before.  Listen, I didnt realize you could be detected at EOT and still clear ; Does this really happen??  UND seems to be the holy grail, so with my count of 29 at EOT, I assumed it was a failure.  Various people told me it might not be a failure and not to judge til I get the 12 wk post treatment result..   

Paul,

I think you are looking at this positively and in the right way.  Another thing to consider is the precision of the test itself.  I have no clue about the test for viral loading.  But my professional background has taught me that EVERY test has precision associated with it.  That's why experimentalists replicate tests to produce one result.  Not saying your test was inaccurate, but 29 is such a low measurement for a test that detects in the millions, it may not be significantly different than zero.  To put it another way, you are likely within the fog of the test away from zero.  Also, there is probably a lower detection limit at or below which you are considered zero viral loading.  i think some other posters have alluded to that.  Anyway, I'm betting that you have cleared the virus and hoping for you to have good lab results later.  Good luck!

Bob

[Katie]

Paul,

I think you are looking at this positively and in the right way.  Another thing to consider is the precision of the test itself.  I have no clue about the test for viral loading.  But my professional background has taught me that EVERY test has precision associated with it.  That's why experimentalists replicate tests to produce one result.  Not saying your test was inaccurate, but 29 is such a low measurement for a test that detects in the millions, it may not be significantly different than zero.  To put it another way, you are likely within the fog of the test away from zero.  Also, there is probably a lower detection limit at or below which you are considered zero viral loading.  i think some other posters have alluded to that.  Anyway, I'm betting that you have cleared the virus and hoping for you to have good lab results later.  Good luck!

Bob

I absolutely agree with you, Bob!  Thanks for your educated opinion on this.

Katie

[Lynn K]

Hi Lovinglife

You will be tested while on treatment to make sure nothing is going sideways and especially in light of your existing kidney concerns.

I also got this from the Harvoni prescribing Information sheet the paper that come with every prescription that most of us just throw away.

http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf

8.6 Renal Impairment

No dosage adjustment of HARVONI is required for patients with mild or moderate renal impairment. The safety and efficacy of HARVONI have not been established in patients with severe renal impairment (eGFR <30 mL/min/1.73m2) or ESRD requiring hemodialysis. No dosage recommendation can be given for patients with severe renal impairment or ESRD [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

and some super technical stuff

Patients with Renal Impairment: The pharmacokinetics of ledipasvir were studied with a single dose of 90 mg ledipasvir in HCV negative subjects with severe renal impairment (eGFR <30 mL/min by Cockcroft-Gault). No clinically relevant differences in ledipasvir pharmacokinetics were observed between healthy subjects and subjects with severe renal impairment.
The pharmacokinetics of sofosbuvir were studied in HCV negative subjects with mild (eGFR ≥50 and <80 mL/min/1.73m2), moderate (eGFR ≥30 and <50 mL/min/1.73m2), severe renal impairment (eGFR <30 mL/min/1.73m2), and subjects with ESRD requiring hemodialysis following a single 400 mg dose of sofosbuvir. Relative to subjects with normal renal function (eGFR >80 mL/min/1.73m2), the sofosbuvir AUC0-inf was 61%, 107%, and 171% higher in mild, moderate, and severe renal impairment, while the GS-331007 AUC0-inf was 55%, 88%, and 451% higher, respectively. In subjects with ESRD, relative to subjects with normal renal function, sofosbuvir and GS-331007 AUC0-inf was 28% and 1280% higher when sofosbuvir was dosed 1 hour before hemodialysis compared with 60% and 2070% higher when sofosbuvir was dosed 1 hour after hemodialysis, respectively. A 4 hour hemodialysis session removed approximately 18% of administered dose [see Dosage and Administration (2.2) and Use in Specific Populations (8.6)].

Hope that helps a little.

If your doctor feels you should do OK with the 12 weeks I would do it if I could. There have been some studies that associate hep c with renal impairment although the link is unclear. I would want to be sure I get rid of the hep c.

Good luck whatever you decide

[Bob V]

Hi lovinglife
I was a dialysis nurse for 20yrs so I understand your caution with Harvoni. I'm sure you had a CMP pre tx, if your renal function was an issue I would hope your doc would inform you.

 I agree you should have this conversation with your doctor.

FWIT: If he says no renal issues I would go 12 weeks.

[Katie]

Thanks Paul, and yes I did read that somewhere.  I've read so much I am not sure where.  I figure the Harvoni is still working for awhile even after the last pill AND your immune system is working better than it has in years.  Perhaps those little alien buggers left over are damaged enough where they can no longer replicate (that is purely my thoughts) so I think we just have to wait it out and see what happens.


Katie

Hi Paul,  I just read a new post from bh4sons and she is now UD at 12 week post treatment.  Thought you'd be interested in this.  This is encouraging!   

I hope it is OK to share her quote on this thread, so please let me know if this isn't acceptable Lucinda.

Katie

Quote from: bh4sons on December 24, 2014, 11:57:08 AM

I just completed S/O about 4 weeks ago.  The counts went down from 2.9M to 360 after one week and non-detected at 6 weeks (didn't have it checked between week 1 and week 6).

I had another blood test 2 weeks after completing the treatment.  Which I followed to the T.  I don't drink alcohol (since about 1977).

I saw my doctor this past Monday, fully expecting that the results would be non-detected (from my 2 week labs).  I was surprised that the viral load was 600.

I had labs done Monday afternoon, to make sure the 2 week labs were accurate.
Needless to say, I was disappointed and hoping that the 600 reading was a blip.  However, I recognize that's probably not the case.

Not sure exactly why the counts were showing 600 on the 12/8 test, but my 12/22 labs came back as NOT DETECTED!

Not sure what that means for the future, but I'll take it!

[dragonslayer]

Katie, thanks for posting that.. In her case, it really seems that her 600 reading was from a false positive.  I think it would be unrealistic for me to expect that my 29 reading was also a false positive.   Ill know for sure in a couple of months.  Expecting the worst; hoping for the best...

[Katie]

Paul,  I would think that way too. It's a defense mechanism, huh?  I read something today on the info thread on this forum that was interesting.  It said the blood level diminishes quicker than in the tissue of the liver.  That is why the duration of treatment is critical and they have the guidelines on the length of treatment.  So some that have the early UD with the blood draw could very well still have the virus working in the liver.  It's a scary thought, and brings back what a visiting doctor told me...."it doesn't matter what your blood VL is, it is what is happening in your liver."  They ran tests comparing the blood levels to biopsies and figured that out, so evidently the 12 & 24 tests are checking the possible replication (which we both knew) and so I understand the process better.  That isn't really good news in your case, but wanted to share it with you as I for one really want to understand the process, and so many of the reports are beyond my comprehension, even with my biology background, that I don't get much out of it.  I never did like statistics as I prefer hard facts, like 1+1= 2 without the + or - for error!

Talk again to you soon.

Katie

[MEG]

Relative to subjects with normal renal function (eGFR >80 mL/min/1.73m2), the sofosbuvir AUC0-inf was 61%, 107%, and 171% higher in mild, moderate, and severe renal impairment, while the GS-331007 AUC0-inf was 55%, 88%, and 451% higher, respectively.

@Lynn, thanks so much for posting those. I'd seen them last night and bookmarked it but you made it easier!

I think I may have found the reason why my doctor prescribed just 8 weeks---although by other criteria(VL under 6mil, no liver disease)---he was correct, but after discussions here last nite and today, I was feeling a bit apprehensive about not receiving the full 12 weeks.

 I learned that I have mild kidney impairment. My creatinine is 0.89 and my EFGR is 76---which is considered mild kidney impairment(below 80).  When I see how much higher the % of Sofosbuvir and ledipasvir were even in the mild category, I'm feeling better that even though I'm prescribed 8 weeks, my body is getting more prolonged or higher exposure so that Harvoni can kick HCV's $%$#%$?

Am I interpreting this correctly? I was a pedi ICU nurse for many years and should know this!

Thanks..I hope you're having a great day.

[Lynn K]

No one has said anything to me about kidney impairment but my EFGR is 64.48 and my EGFR (BLACK) is 74.74 currently which is down from a year ago of EFGR 72.96 and EGFR (BLACK) is 84.56. I believe, but I could be incorrect, it isn't a concern until less than 59

My current creatinine is 0.98 and was 0.89 last year when I wasn't on treatment. But those are still in normal range.

Dunno about you last comments as I am a shop machinist type and not a medical pro. But I figure it is what it is, and it will work like it does given our on set of circumstances.

For folks who are treatment naive with minimal liver damage and low viral load many insurers are preferring patients treat for 8 weeks and th eresults have been good for that group with that treatment.

So we will cross the end of treatment 12 week post test for SVR when we get there and not one minute sooner no matter how much we ponder the stats.

We will get the final results the fates decide.

Good luck on treatment