Options For Patients Who Fail Harvoni Treatment

[Hep Editors]

Turns out, people with genotype 1 of hepatitis C virus who have failed Harvoni (ledipasvir/sofosbuvir) treatment have a pretty decent chance of a cure from a second round of the drug lasting 24 weeks.

In a recent retreatment trial, 71% of study members achieved a sustained virologic response 12 weeks after completing a second therapy.

Note: Those who had gotten their first Harvoni treatment for eight weeks had an 80% cure rate, while those who had failed a 12-week regimen had just a 46% cure rate. 68% of those with cirrhosis were cured on a second try.

For more info: http://www.hepmag.com/articles/Harvoni_retreatment_2501_27162.shtml

[Cute]

The results of the two trials of the drugs used in combination - daclatasvir, asunaprevir and beclabuvir - are published online by JAMA.

The trials, one including people with liver disease, the other without, both saw eradication rates of around 90% and more against a measure of aviremia called sustained virologic response (SVR).

These treatment-experienced groups still achieved SVR12 rates of 87% for patients receiving the drug combo alone and 93% for patients with ribavirin added.

Overall, the authors conclude, SVR12 was achieved by 93% of 202 patients with genotype 1 infection and compensated cirrhosis after 12 weeks of treatment with the fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir, with or without Ribavirin.

"These two studies add to the armamentarium of all-oral interferon-free regimens that have revolutionized management of hepatitis C, not only for patients who are treatment-naïve with no significant liver disease but also for those who are treatment-experienced and those with cirrhosis."

http://www.medicalnewstoday.com/articles/293440.php

[pappy]

Sounds nice but my doctor does not want to redo Harvoni possibly because of cost but also because of possibility the virus has already developed immunity to drug .

Turns out, people with genotype 1 of hepatitis C virus who have failed Harvoni (ledipasvir/sofosbuvir) treatment have a pretty decent chance of a cure from a second round of the drug lasting 24 weeks.

In a recent retreatment trial, 71% of study members achieved a sustained virologic response 12 weeks after completing a second therapy.

Note: Those who had gotten their first Harvoni treatment for eight weeks had an 80% cure rate, while those who had failed a 12-week regimen had just a 46% cure rate. 68% of those with cirrhosis were cured on a second try.

For more info: http://www.hepmag.com/articles/Harvoni_retreatment_2501_27162.shtml

[KW2023]

I officially failed Harvoni 12 weeks... I was told "Well you are the first that we have seen, we knew it would happen sooner or later" 

I am devastated.. I was treatment naive.  They will look into resistance testing.
 

[pappy]

Sorry to hear about that guess you will be doing a viekira pak with riba next . I am heading into my last month of a six month long script . Its not as easy as harvoni and the effects are much more than harvoni as well good luck .

[Scoutdoy]

KW, sorry to hear that you relapsed, or did you ever go undetected? Hopefully with new technology you can get a new treatment. Hopefully you don't test positive for the resistance. Is it possible for it to still clear even though you tested detected at the 12 week mark. I swear I read of a similar situation on the Harvoni relapse thread of a couple of people who tested positive at 12 weeks but then when undetected. I am gonna look for that thread


Scout

[Scoutdoy]

KW here is the article


http://m.cid.oxfordjournals.org/content/early/2015/03/02/cid.civ170.abstract



Scout

[Scoutdoy]

KW I found the thread of people who were detected at end of treatment and even some detected past end of treatment who then became undetected....it's remarkable and I think you should read them

http://forums.hepmag.com/index.php?topic=2383.0


Scout

[dragonslayer]

I officially failed Harvoni 12 weeks... I was told "Well you are the first that we have seen, we knew it would happen sooner or later" 

I am devastated.. I was treatment naive.  They will look into resistance testing.

I'm one of those who was detected at EOT and even at 7 wks post treatment, but went on to clear by 12 wks post treatment.  Please list all your viral load tests and their results, ie, when you had them relative to treatment period, and their results.  It will help us interpret  whats going on.

Thanks.

[Lynn K]

Hi Pappy

Treatment with viekira pak is not recommended for Harvoni failures due to cross resistance issues

Per the current AASLD guidelines for patients who have failed a treatment with any HCV nonstructural protein 5A (NS5A) inhibitors like ledipasvir/sofosbuvir (Harvoni) amoung others the recommendation is as follows for GT 1:

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 minimal liver disease, deferral of treatment is recommended, pending availability of data.

Rating: Class IIb, Level C

 

For patients with cirrhosis or other patients who require retreatment urgently, testing for resistance-associated variants that confer decreased susceptibility to NS3 protease inhibitors and to NS5A inhibitors is recommended. The specific drugs used in the retreatment regimen should be tailored to the results of this testing as described below. Treatment duration of 24 weeks is recommended and, unless contraindicated, weight-based RBV should be added.

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.

No data are yet available on the retreatment of patients for whom prior treatment with PrOD has failed. However, studies that have evaluated patients whose virus did not respond to PrOD have reported the presence of RAVs that confer decreased susceptibly to NS3 protease inhibitors (eg, paritaprevir), NS5A inhibitors (eg, daclatasvir, ledipasvir, ombitasvir), and nonnucleoside polymerase inhibitors (eg, dasabuvir). Based on these observations, patients for whom treatment with PrOD did not result in an SVR should have HCV treatment deferred in the setting of mild liver disease, and for those with advanced fibrosis, testing for RAVs should be performed.

Data on the retreatment of patients for whom prior treatment with ledipasvir/sofosbuvir has failed are very limited. In a pilot study, 41 patients with and without cirrhosis who did not achieve an SVR with 8 weeks or 12 weeks of ledipasvir/sofosbuvir were retreated with 24 weeks of ledipasvir/sofosbuvir. SVR12 rates varied according to the presence or absence of NS5A inhibitor RAVs. Among 11 patients for whom NS5A inhibitor RAVs were not detected, SVR occurred in 11 of 11 (100%); in contrast, among 30 patients for whom NS5A inhibitor RAVs were detected, SVR occurred in 18 of 30 (60%). Importantly, NS5B inhibitor RAVs (eg, S282T) known to confer decreased activity of sofosbuvir were observed in 3 of 12 (25%) patients for whom the retreatment regimen was not successful. Similarly, in the OPTIMIST-2 study in which patients with cirrhosis were treated with simeprevir and sofosbuvir, the presence of NS3 RAVs, namely the Q80K polymorphism, led to a decreased SVR rate in patients with HCV genotype 1a infection. SVR occurred in 25 of 34 (74%) patients with HCV genotype 1a and the Q80K RAV and in 35 of 38 (92%) patients with HCV genotype 1a without the Q80K RAV. Based on these data, retreatment for patients for whom an NS5A inhibitor-containing regimen has failed should be considered in the context of retreatment urgency and the presence or absence of RAVs to inhibitors of NS3 and NS5A. Further, based on limited data, RBV is recommended as part of all retreatment regimens for patients in whom prior treatment with NS5A inhibitors has failed. Although no data exist, consideration may also be given to the addition of PEG-IFN to the retreatment regimen in patients who are eligible for this agent; PEG-IFN will have antiviral activity regardless of the RAVs present.

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

[Lynn K]

Hi KW2023

As Dragon slayer said it is possible you could still clear the virus.

You posted you were " Minimally detectable at week 12" was that at EOT or 12 weeks post?

What is minimally detectable? Dragon and several others here were also " Minimally detectable at week 12" and went on to be SVR at a later time.

Don't give up just yet

Lynn

[KW2023]

Sorry to hear about that guess you will be doing a viekira pak with riba next . I am heading into my last month of a six month long script . Its not as easy as harvoni and the effects are much more than harvoni as well good luck .

Thanks Pappy
 I am not a candidate for any therapy that includes  riba as I was on it for 2 weeks and did not tolerate it.  I did not want to stop but since I developed such severe side effects my MD will not let me continue to take it. They added it at week 8 as I was considered a "slow responder" at that time.

Due to the severe side effects I was given an extra 4 weeks of Harvoni.(gift from my insurance per my MD) I posted  that I was a non responder as my MD said that if I was ND at 12 weeks I will not be at 16 weeks. But after reading  some of the graciously posted articles and posts  I have some hope. Thanks for the kind words and hope.

[KW2023]

KW, sorry to hear that you relapsed, or did you ever go undetected? Hopefully with new technology you can get a new treatment. Hopefully you don't test positive for the resistance. Is it possible for it to still clear even though you tested detected at the 12 week mark. I swear I read of a similar situation on the Harvoni relapse thread of a couple of people who tested positive at 12 weeks but then when undetected. I am gonna look for that thread


Scout

Hi Scout,
 Thanks for the information.. I have some hope now.

[GLCII]

KW2023

They now have Hep C by the throat. Harvoni is just the first step and a good one in finding a cure. The next round of new drugs is going to be the one to deliver the knockout punch and illiminate it. It think you have alot of hope, of being cure, in the very near future. Most of us here failed multiple treatments prior to harvoni and know exactly how you feel. I think your time is coming very soon.   

[Scoutdoy]

KW....seriously....4 weeks from now I bet you are undetected! You'll see.... Message me when you do



Scout

[Lynn K]

yes you situation looks very similar to the other folks who eventually made SVR

Seems like guessing here that the test is picking up maybe dead and dying virus or fragments of virus but anyway not able to reproduce virus.

See if you can get a 4 week post HCV RNA by PCR most relapses occur in th efirst 4 weeks post you will likely see a rise in liver functions and the viral load will jump back to pretreatment levels if there has been a relapse. If not a huge increase in viral load and hopefully not detected at that point you could still make SVR and your doctor will learn about a different scenario of post treatment testing results.

Wishing you only good news
Lynn