Failed Harvoni - NP Recommends Viekra Pak / Ribavirin

[Pete]

Been awhile since I've posted here.  I failed 12 weeks of Harvoni tx (July) and let things stew for awhile before making another move.

I read a post on this forum that recommended RAV testing before choosing other tx options. Thank You!  So I requested the testing, and just got the results. The results are posted below along with a recommendation from my PA to start Viekra/riba for 24 weeks.  Anyone see a problem / potential contradiction, or should I give it another shot?  Six months of riba seems like that could rough. 

HCV Ns5A
Daclatasvir - Resistance not predicted
Ledipasvir - Resistance Predicted
Ombitasvir - Resistance Not predicted
     
Ns3 
Boceprevir Resistance not predicted
Paritaprevir Resistance not predicted
Simeprevir Resistance Predicted
       
PA Comments:
With the above results, the best option for treatment for a cure would be Viekra Pak with Ribavirin for 24 weeks. The ombitasvir, and paritaprevir are part of Viekira Pak.

Thanks, and I wish a wonderful Holiday Season!

Pete

[malou]

Ok Pete, so from a clinical perspective (I am an NP with HCV), you must have some mutations in your viral profile, that were resistant to the drugs in Harvoni.  I am curious where you are clinically, do you have fibrosis or cirrhosis, and what treatments have you us d I n the past?  ML

[Pete]

Hello ML and thanks for your reply. 

Age - 63 Diagnosed 2002
Geno -1a
Biopsy Score 2006 - 3/3
Diagnosed with Compensated Cirrhosis 12/2014
3/9//15  - Started Harvoni 12 weeks (Failed SVR)

Things looked great after 12 weeks of Harvoni, but post 4 week labs indicated the virus was back with V/L up over a million.  I was treatment naive until the Harvoni.

I feel fine in terms of overall health and energy at this point.  My son is to be married in June, so I really don't want to get knocked on my butt from 24 weeks of riba. Although my PA said that if it the sx gets bad, I could discontinue the riba.  But she encouraged I stay with it as long as I could stand it.

pete

[KimInTheForest]

If I were in your position, Pete, I would try for 24 weeks of Sovaldia + Daklinza, and avoid the ribavirin that way. You resistance assessment says you are resistant to ledipasvir, but does not mention sofosbuvir. So in all likelihood the sovaldi (sofosbuvir) would work for you. And it looks like the Daklinza (daclatasvir) would too.

24 weeks of Sovaldi/Daklinza is one of the recommended treatments for Geno 1a with cirrhosis (tx naive). Chart here:

http://www.hepmag.com/articles/2512_18756.shtml

Good luck!
kim

[Lynn K]

Per the AASLD guidelines (a little more than half way down)

http://www.hcvguidelines.org/full-report/retreatment-persons-whom-prior-therapy-has-failed

"Recommended regimen for patients in whom previous treatment with any HCV nonstructural protein 5A (NS5A) inhibitors has failed (including daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir plus dasabuvir)."

"For patients with cirrhosis or other patients who require retreatment urgently, testing for RAVs that confer decreased susceptibility to NS3 protease inhibitors (eg, Q80K) and to NS5A inhibitors should be performed using commercially available assays prior to selecting the next HCV treatment regimen. For patients with no NS5A inhibitor RAVs detected, retreatment with ledipasvir/sofosbuvir and RBV for 24 weeks is recommended. For patients who have NS5A inhibitor RAVs detected and who do not have NS3 inhibitor RAVs detected, treatment with simeprevir, sofosbuvir, and RBV for 24 weeks is recommended. For patients who have both NS3 and NS5A inhibitor RAVs detected, retreatment should be conducted in a clinical trial setting, as an appropriate treatment regimen cannot be recommended at this time."

So based on all that either you go with your doctors recommendations as it looks like you may have a shot per you testing or see if you can qualify for a clinical trial as the AASLD suggests if you can find one.

I do see that Daklinza (daclatsvir) an Ns5A inhibitor on your report as-Resistance not predicted is apparently also a possibility but per the prescribing information it currently is only approved for GT 3 in the US so for you it would be off label. That doesn't mean you cant be prescribed it but you may have to fight with your insurance to get it.

Oh yeah one other thing about Viekira Pak they have been some problems for patients with Child B and C cirrhosis and the recommendation for a Child A patient is:

"For patients with CTP class A cirrhosis, the unlikely but real possibility of drug-induced liver injury should be discussed with the patient. If the decision is made to initiate treatment with PrOD or PrO, close monitoring of total and direct bilirubin and transaminase levels every 1 week or 2 weeks for the first 4 weeks is recommended to ensure early detection of drug-induced liver injury. Also, educating patients about the importance of reporting systemic symptoms such as jaundice, weakness, and fatigue is strongly recommended. The regimen should be discontinued immediately if drug-induced liver injury is detected. If a patient is already taking PrOD or PrO and is tolerating the regimen, laboratory monitoring as above without discontinuation is recommended unless there are signs or symptoms of liver injury. If heightened monitoring cannot be provided in the first 4 weeks of therapy with PrOD or PrO in patients with cirrhosis, the use of these regimens is not recommended."
 
Having cirrhosis I can definitely understand your concern but I have been living with hep c for 37 years and cirrhosis for 8 years it is tough to wait for something better I had no treatment options 5 years after I was diagnosed with cirrhosis until Sovaldi and Olysio were approved. I failed that treatment but was finally cured with Harvoni and Ribavirin.

Cirrhosis is a slow disease from compensated to decompensated you still have time to find a treatment that works.

Good luck and hoping this treatment is the last one you need to do
Lynn

[Pete]

Hello Kim - First off congrats on your SVR,  Good for you!

I noticed on the link you provided that the chart stated recommendations for Treatment Naive.  These 2 protocols look to be both with/without riba when prescribed for 24 weeks.

Daklinza + Sovaldi for 12 weeks (no cirrhosis) or 24 weeks with/without ribavirin (cirrhosis)

Viekira Pak + ribavirin for 12 weeks (no cirrhosis)or 24 weeks with/without ribavirin (cirrhosis)

Seems too many options choose from. I'm not approved for a second try yet.  I really doubt I'll get a third shot if I go with the wrong protocol.   

Lynn - Thank you again for what you do for everyone here.  It recall it was your post that linked to the AASLD your article that tipped me off to RAV testing.  One would think my PA would have recommended that.   Appreciate the heads up on the Viekira Pak potential risks.  I learn more here than from my health care provider.

Regards,

[Pete]

This is new...  I been asked to participate in a research study of drugs called ombitasvir, paritaprevir (ABT-450)/ritonavir, disabuvir, ribavirin (RBV) and Solvaldi.  The combination of ombitasvir, paritaprevir (ABT-450)/ritonavir, and disabuvir is also called Viekira Pak.

So this is essentially Viekira Pak with RBV with Solvaldi added for 24 weeks.  While I suspect many would jump at the chance for free TX, (plus getting paid a nominal fee), I have reservations about the Viekira Pak warnings with regards to cirrhosis.  By all measures I am Class A, and do not feel ill in any way.  All my recent LFT's look good with the exception of slightly elevated enzymes.

The Abbvie consent form to participate in the trial is quite lengthy.  The numerous side effects, and potential risks are spelled out quite clearly.  LFT's would be monitored at the following intervals; 1, 2, 3, 4, 8, 12 weeks and monthly after that. 

Apparently any liver damage would occur early in TX if at all.   Although it is stated those risk are small, it simply scares the heck out me to be frank.

So here I am at the crossroads again.  My wife is not on board, my son is getting married in June, both say it's my choice.  While I made it through Harvoni unscathed,  I have reservations with this concoction of multiple drugs.  I've got maybe 48 hours to decide.

If anyone is interested in viewing the consent form, pm me your email addy and I share the document.  It's simply too long to post here. 

Best to everyone,

Pete

[Lynn K]

As far as the warnings you are child A so it really shouldn't be a problem and you will be well monitored.

I would be most hesitant about the ribavirin but it is often not as bad when not taken with interferon.

Yeah it is up to you. You want to be cured and you do have cirrhosis so you do need to be cured before much more damage can occur.

Gee your getting paid? I was in a couple of trials and all I got was the medicine and testing for free. I didn't do it for the money or free meds there was no treatment for me at the time. Had there been my insurance would have paid for treatment I was just trying to get cured.

Do they have an idea if it will work for you? Does your doctor think this is a good treatment or should you wait for a different trial like maybe with Daklinza or something else?

Congrats on your son's upcoming wedding

Good luck

[Pete]

Thanks Lynn - Yep, the wedding is a huge excitement for my family.

The doctor conducting the trial informed me that I was referred by my hepatologist, both think I'm an ideal candidate and a really good shot at SVR.   I'll hope to get a chance to speak directly with my hepatologist before deciding. I went back and read the fine print about the compensation.  I'll be compensated on a per visit basis, 15 visits over 72 months.  Apparently alot of post TX analysis.  They even want my DNA... I've never been part of trial like this and I know not everyone gets a chance. 

I did ask if the RBV turned out to be too much to handle, if I could stop the RBV and still continue the trial and was told yes. 

Thanks for reply,

[HazelAustralia]

Hi Pete,

I don't have cirrhosis, but the 'contract' that I had to sign prior to getting access to Vieira Pak in a compassionate trial was very lengthy and it was explained to me that they legally had to inform me of any possible side effect. I wonder if that normalises that part of the paperwork for you - I don't know?

I wish you well with your decision, the time frame must make it feel more difficult I think.

Hazel

[Pete]

I spoke with my Hepatologist yesterday.  Super nice lady, seemed genuinely concerned about my condition.  She assured me that if i decided to participate in the trial, I would be closely monitored for signs of any trouble. 

She did mention that one option for failed Harvoni  patients was another 24 weeks of Harvoni with RBV.  However, SRV rates drop to about under 80%.  She felt the ABT-450 trial was my best option at this point to clear the virus.

I've decided to start down this path and have an appt with the clinician the first week of Feb to go over the pre-checklist.  So my options are still open right now...

More to come, 

[Lynn K]

I had the feeling you are leaning towards doing the trial.

I am like that too I have something wrong so I need to do my darnedest to try to get it fixed hence my 3 attempts with interferon based tx even though with each treatment my odds were lower and lower I still have to try.

Good on you dragon warrior and wishing you the best of luck with the trial

Charge!!!!!!!!
Lynn

[HEPful Guy]

Given your resistance testing, you have a great chance of clearing the virus with the therapy because you show no cross-resistance to the Viekira. Normally Viekira pak is a terrible option for patients with cirrhosis because of the potential for decompensation. If you're going to be in a trial though, i'm sure you will be monitored at a much higher intensity than a normal patient so this should be a great option. Another potential option might be to see if you can get your insurance to approve you for Zepatier, which has great clinical trial data.

[Coach Mike]

If all else fails, you can get 24 weeks of generic. sofosbuvir and daclatasvir for under $2000. Dr. James Freeman is about to provide some spectacular results for the EASL regarding generic efficacy.
It will be a game changer.
CM

[KimInTheForest]

If all else fails, you can get 24 weeks of generic. sofosbuvir and daclatasvir for under $2000. Dr. James Freeman is about to provide some spectacular results for the EASL regarding generic efficacy.
It will be a game changer.
CM

That is such exciting news, CM, about the efficacy of the generics. These worldwide Redemption eTrials are really yielding some important data. I can't wait to see what Dr. Freeman releases about it.

kim