failed harvoni-what next

[sharon123]

any other options

[dragonslayer]

Sorry about that Sharon..  Might help people respond if you flesh out your post some with  more details about your case and treatment...

[sharon123]

hi--4th treatment--cleared with harvoni but came back --doc. wants new data on new drug just approved for non responders-- --works for most but 5% end up being non-responders--- I know it is too new to have many people able to give info-- just checking --thanks again--shar

[Lynn K]

How many weeks were you treated? Did you also take ribavirin or just harvoni?  Do you have liver damage? Cirrhosis? What were your prior treatments? Is your doctor going to have resistance testing done? What kind of doctor are you seeing? Do you know the name of the treatment he is considering? There are several new ones.

Sorry to see you relapsed good luck with next treatment

[morab]

sharon123
Hang in there! Keep us posted and let us know your genotype and some other stats might help. There is a new drug out now that may help you battle the beast!
Morab

[sharon123]

thank you all for support--was treated 12 weeks--5 years ago was stage 2  but think I may have progressed since then -- liver tests stay at around twice normal range .  My real concern now is HCV really jumped in 6 months.  Tired all the time but no cirrhosis.  Don't understand doc saying he would be more concerned that number went down as it would suggest more liver cells dying But I obviously have more virus in liver.  Would love to find some hope--thanks for "listening"---be well all..........

[sharon123]

anybody out there that failed harvoni & now on anything else?

[Lynn K]

You failed Harvoni 5 years ago? Harvoni was only approved for prescription in Oct 2014 were you taking harvoni as part of a clinical trial?

If you are talking about liver function tests like ALT and AST those only indicate something is injuring your liver not the degree of injury. You can hive hive ALT and AST and have no liver damage or have normal levels and have liver damage.

When you say HCV really jumped do you mean your viral load? Viral load varies all the time and has no relationship to severity of illness.

Feeling tired is the single most common symptom most people report with hep C. Cirrhosis does not really have symptoms early on. When symptoms do develop the most common noticible sumptom is lower leg edema that is swelling of lower legs also called pitting edema. Other symptoms are less noticible at least at first like ascities which is retaining fluid in the abdomen which at first is only noticible on ultrasound but in advanced cirrhosis can progress to the point the patient looks pregnant and the fluid will need to be drained periodically as it does return.

I had liver biopsies after I was diagnosed with hep c back in late 1990. Had an initial and repeated every 5 years. I went from F1 to F2 to F3 and finally was diagnosed F4 aka cirrhosis in January 2008. I treated 3 times with interferon based treatment over the years and each time I had no response to treatment. When the new gen medicines were approved I treated with Sovaldi / Olysio for 12 weeks March to June 2014 but was found to have relapsed in Sept 2014 which was 12 weeks after I has stopped treatment. When Harvoni was approved in Oct 2014 I then started on 24 weeks of Harvoni and later added ribavirin for 15 of those 24 weeks as with my treatment history and cirrhosis status my doctor agreed it might be a good idea.

Harvoni is actually a combo medicine of Sovaldi and Ledipasvir so in that sense I did treat with a component of Harvoni a related medicine. There are other patients I am aware of who treated with Harvoni for 8 weeks and later treated with Harvoni again but for longer times and possibly with the addition of ribavirin and were cured.

But per the AASLD guidelines you need to be tested for RAV resistance associated variants 

[Lynn K]

I don't see where you mention your genotype are you genotype 1?

This is from the AASLD about retreatment of patients who have failed Harvoni and are genotype 1. 

Ledipasvir/sofosbuvir failures

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. (Lawitz, 2015b) 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. (Lawitz, 2015b) 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. (Lawitz, 2015) 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, ribavirin 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.

Retreatment approach and potential regimens (including other NS5A regimen containing failures)

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 or sofosbuvir/velpatasvir, both with ribavirin, 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 ribavirin for 24 weeks is recommended. For patients who have both NS3 and NS5A inhibitor RAVs detected there are several small studies that provide some insight on salvage regimens. Limited data suggest a retreatment approach based on sofosbuvir combined with either elbasvir/grazoprevir or PrOD may be efficacious. (Lawitz, 2015e); (Poordad, 2015a) In a retreatment arm of the C-SWIFT study, 23 patients who had failed shorter courses of elbasvir/grazoprevir plus sofosbuvir were retreated with 12 weeks of this combination plus weight-based ribavirin. In a per protocol analysis a 100% SVR12 rate was achieved (23/23), including SVR in 9/9 patients with dual NS3 and NS5A RAVs. (Lawitz, 2015e) A second phase II study of 22 patients, including 14 PrOD failures, evaluated retreatment with 12-24 weeks of PrOD plus sofosbuvir. Treatment duration and ribavirin usage were determined by cirrhosis status, HCV RNA response on therapy, and genotype subtype. SVR12 data was available on 15 patients with 14/15 (93%) attaining SVR12. Based on these limited data, patients with dual NS3 and NS5A class RAVs may be retreated with elbasvir/grazoprevir plus sofosbuvir with weight-based ribavirin for 12 weeks or PrOD plus sofosbuvir for 12 weeks in genotype 1b and 24 weeks with weight-based ribavirin in those with genotype 1a. If these regimens are unavailable, retreatment should be conducted in a clinical trial setting, as an appropriate treatment regimen cannot be recommended at this time. Another approach in patients with prior non-response to NS5A-containing therapy has been studied in genoptype 1, 2, and 3 patients who did not respond to velpatasvir-containing regimens including sofobuvir/velpatasvir and sofosbuvir/velpatasvir/GS-9857. (Gane, 2016) Retreatment with sofosbuvir/velpatasvir with ribavirin for 24 weeks yielded high overall response rates (91% or 59/65). Among genotype 1 patients, 97% (33/34) achieved SVR. Baseline NS5A RAVs did not appear to effect SVR rates. In 34 genotype 1 patients, 6 patients had NS5A RAVs prior to retreatment, all of whom achieved SVR. Although data is extremely limited, retreatment with sofosbuvir/velpatasvir + ribavirin for 24 weeks should be considered in genotype 1 patients who have not responded to prior NS5A-based therapy, especially if there is urgency for treatment.

[HHburme]

I started Harvoni in December 2014 and relapsed at SVR12 labs. Started a clinical trial study for Gilead SOF/VEL GS-9857 in February 2016. Just got the call this morning that I'm UNDETECTED SVR12, cured !!!!! This drug should be available within one year and is the answer. I experienced minor SE like pain in knees, joints. I was crushed after failing Harvoni but pressed on and was able to get into the study for this incredible drug. Thanks to Gilead and my team of doctors for letting ne be the guinea pig for this drug. Feel really blessed.
Fight the Good Fight !
John

[FutureThinker]

HH, thanks again for having the courage and strength to participate in this study and help rid this planet of HCV.  FT

[sharon123]

thank you so very much John--I know new drug was approved recently but my doc is waiting for more data cause he says if I fail that one -not many options left--would appreciate any more info you have on this drug--specifics--so I can address with my doc.  stay healthy & am so happy for you--I want to join that club too!!! Sharon

[FutureThinker]

This sounds like Epclusa plus another drug (GS-9857).  Apparently still in the trial stages, but he says should be approved in a year ----- that is fantastic news!

Now, just wonder how Gilead will price it.  They put Epclusa $20,000 less than Harvoni, but that is still a very high cost.  FT

[HHburme]

Yes, Epclusa plus a third drug, all in one pill. Less than a year away.