Triple Therapy: Apparent Complete Failure

[AHNOLD]

Hi everyone. I'm new to this board but I've followed it for the past few weeks.

I'm a 29 year-old male and I was diagnosed with Hep C (genotype 1a) in November 2010 after a routine blood test. I, for the life of me, have no idea how I got it. The most likely candidate is that I got it just after birth in 1981 (I was a blue baby and needed some blood transfusions).

Anyway, I got a biopsy done this past January and the results were good: Stage 1 Fibrosis, no red flags.

I started triple therapy with Incivek, Ribavirin, and Pegasys around mid-September. Other than the first night of my shot, I have had basically zero side-effects. I still lift heavily, row, go to work, travel almost weekly,etc... Weekly blood tests hardly registered any changes in my hemoglobin levels, platelet levels, etc... However, the 4-week results were surprising, to say the least.

My viral load count went from 840,000 before to 620,000 after 4-weeks of strict treatment. Obviously treatment has failed and I'm curious to see if anyone here has received similiar results. I know data is limited on this, but does anyone know (either through personal experience or anecdotally) how I could be such a significant non-responder? Are there any indicators that could explain this?

I'm very active and I have a large appetite so I've had no problem eating the gobs of fat necessary to consume Incivek and, to a degree, Ribavirin. My diet is pretty good. I avoid fast food, I don't eat out often, I eat organic when I can, and I consume plenty of protein and water (a gallon+ a day) given my active, gym-going lifesyle.

I'm going to see the doctor on Tuesday to get answers to my questions and map out a plan. But I just want to see what I could glean from this community. Thanks!

-J

[pjhep80]

i totally think that no side effects = not working, first time i treated it did not effect me at all.. not so this time haha...

that just sux it did not work for you but  like everyone was saying you have very minimal damage and are living healthy and new stuff coming out soon so hang in there !!!!!!

[rockymoe]

Hang in there! I was diagnosed in 99 and was stage 1.  am on my 8th treatment. I am a relasper non responder. I am on VIC now and so far good news. It's like I'm always waiting for my next poison. I am stage 3 now.

[penn1023]

the docs i've spoken with say that in maybe 5 years we will no longer be using interferon to treat HCV

That's what mine said too. Hopeful for the future.

[orphanedhawk]

All of the treatments are based on statistics, none claim 100% viral response.
You are fortunate, your liver isn't badly damaged.
Best of luck,
OH

[coeric]

opps, that should have read interferon-free clinical trials not interferon-clinical trials

[coeric]

Willy, as usual, has a great point with the decreasing importance of one's own innate immune system with the new direct acting antivirals.  the docs i've spoken with say that in maybe 5 years we will no longer be using interferon to treat HCV. i think if i were in your shoes i would take a watchful waiting approach.  you could also look at the interferon-clinical trials that are beginning.
eric

[coeric]

dointime has a good point about breakthrough. it sure would have been nice to know what your viral load was at less than 4 weeks.  we agree that it does appear that you did not have a good response to the interferon.  i think you would have seen a larger viral load drop if you had.  as others have suggested, i would ask the doc to check the IL28b

the most prolific poster here using larger doses of ribavirin is jmjm530. his personal page is.  www.medhelp.org/personal_pages/user/90290
he used the work of Lindahl, cited below, as inspiration.  he went on to SVR, but was very ill during treatment, and required hospitalization.


Hepatology. 2005 Feb;41(2):275-9.
High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C.
Lindahl K, Stahle L, Bruchfeld A, Schvarcz R.
Source
Department of Infectious Diseases, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden. karin.***@****
Abstract
Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. At follow-up (>or=24 weeks posttreatment), nine of ten patients had undetectable HCV RNA and thus were cured by standard definitions. In conclusion, a high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation.

[Willy50]

If ones vit D levels were very low sometimes it takes time to get them up, from what I've heard, I don't claim to know.  Nor do we know where your levels were.  I wouldn't pin lack of response on missing a few pills. (nor on retreating successfully by taking those few extra pills).

It is not well understood what makes a null or non-responder, many things can be associated with it.  Part of my point is that just because you had a certain response does not mean you are stuck with it.  There are things that can improve immune response.

Further, as treatments advance ones innate immune response may play a smaller and smaller role in getting cured.  The anti-virals (or group of DDA's) will kill the virus regardless of your immune response or genotype, or get it down in short order so that it doesn't mutuate around to a resistant form.  Obviously, getting any issues, BMI, IR, vit D levels, and having proper diet and an exercise regimen will not hurt you next time out.

best,
Willy

[AHNOLD]

Okay, thank you for your insight. It makes me feel better that my treatment may not have been compromised because I was inconsistent with my Vitamin D intake.

[AHNOLD]

Thank you for chiming in. Yes, after watching this presentation that I found in another thread (http://74.43.177.57/courses/2010/pg/pawlotsky/player.html), I'm tending to agree with you. In accordance with what coeric wrote above, it's rare for people to not respond to Incivek. Therefore, it appears I may not be responding to Interferon and/or Ribavirin (either because I have an innate resistance or the dosage isn't high enough).

I'll bring this up with the doctor on Tuesday. I'm also wondering if upping the dosage of both drugs may help? As I said earlier, the side effects of all drugs have been minimal at the current dosage so my body may be able to bear the extra "abuse."

Has anyone used either Ribavirin and/or Interferon above the recommended dosages? If so, did it have an impact that was worth the (potential) extra side-effects?

[dointime]

I don't believe that the PI did not work.  It is much more likely that you had a big initial drop in vl and then resistance kicked in and your vl went up again.  You don't say, so I am presuming that your 4 week PCR was your first one after starting tx.

When I did tela I started at 2 million and went to UND in 15 days.  By week 4 I was back up to 200,000.  I knew because I was in a trial and they were taking frequent bloods.

It is not uncommon for people who have a breakthrough to be misdiagnosed as non-responders.  It used to happen with SOC as well before they started doing pcr's at 4 weeks.  The initial drop in vl was missed.  Even if you never went to UND I would be extremely surprised if you did not get a large initial drop in vl.  There is no such thing as far as I know as a non-responder to a direct PI.

However at the end of the day it looks like your response to ifn is poor, so it still leaves you with much the same choices as a non-responder for your future tx.

good luck
dointime

[coeric]

sorry to hear about your treatment failure.
the following is from the FDA briefing document for telaprevir
"Predominant baseline resistance to telaprevir is rare (< 1% to 2.7%) and does not necessarily preclude achieving an SVR with a T/PR regimen. On-treatment virologic failure during telaprevir treatment is associated with higher-level telaprevir-resistant variants, and occurs more frequently in genotype 1a compared to 1b."
perhaps you have the higher-level telaprevir-resistant variants in addition to an unfavorable IL28B genotype.
eric

[flcyclist]

"However, let's assume for a second that my Vitamin D levels were low. Would that explain my treatment response?"

I also had my vitamin D level tested around week 18 of trt and found that I was deficient.  Since I was und at week 4 & 12, and possibly deficient during this time frame, I'd venture a guess it had little influence on the VL results.  

I've read several recommendations to avoid iron while taking supplements and iron rich foods.  I haven't seen any published references to confirm this, but it is repeated on this forum and by doctors.  Again, probably not a reason for failure, but something to consider.  I wish you the best.

[AHNOLD]

No, I do not take any performance-enhancing drugs. I have one protein shake a day and I eat many grams of protein per day via ground turkey, chicken, lentils, beans, yogurt, cereal, etc....

[AHNOLD]

When I first found out I had Hep C in November 2010 I was told my Vitamin D levels were low (I don't think it was unusually low as my doctor told me to just take a Vitamin D supplement with no specific dosage), so I took daily supplements religiously (1,000 I.U. most of the time and 400 I.U. the remainder) between then and the beginning of treatment.

I also took the Vitamin D supplements during treatment, but not as frequently. Between the 12 pills I had to take daily sometimes I simply forgot to include the Vitamin D pill.

However, let's assume for a second that my Vitamin D levels were low. Would that explain my treatment response? Again, I'll explore this with my doctor but any input is appreciated.

Yes, I did consume more than enough fat with my Incivek. If there's one thing I'm really good at it's consuming massive quantities of food!

Thank you for your input!

[lynda607]

There are still resistance issues after stopping Incivek even if it was only taken for 4 wks.  Perhaps not to the degree if Ahnold taken it for 12 wks but he would not be a candidate for re-treatment with Incivek due to PI resistant variants that develop when the compound is stopped early.

[Mary4now]

Shoot, I weigh 125 and was taking 1200 Riba,
I was also told that resistance is not so much when you just stop taking the drug its when you take it improperly, skipping days, not taking as much, etc. but when you just stop completely it is not a problem with resistance.
I will check on this with the ppl from the study center, they have been an HIV study center for 12 years so I assume they know what they are talking about, they have a very good reputation.  maybe i'm wrong.about the resistance I will check with them next visit
ANHOLD, so sorry about your response.  good think you have little damage, things are changing rapidly and you can benefit from that down the road.  there is lots to learn here.

[lynda607]

A thought occurred to me and I'm wondering if you were taking any type of steroid or performance enhancing drugs given your active weight lifting and gym lifestyle?  Steroids and performance enhancing drugs can interfere with the efficacy of the treatment drugs.

[can-do-man]

Sorry about the news, fact is you had no response, while 1400 riba might have been better 1200 would not have caused this, nor would have changing, testing or doing anything else i've read here........ You gave it your best shot and hopefully new drugs will provide you better results. Though i do agree the lead in would have spared you the third drug and your case is a good reason for one.

You have time on your side so i wouldn't dwell over this..... Best to you going forward.

[Willy50]

My 2 cents; what paen said; you may not have had quite enough riba.(although you took the prescribed amount).  Occasionally it seems to me that a lead in would be a good idea, as if one had been done here you might not even have been administered a PI.

Some folks also find that IR issues may weaken immune response, although that doesn't sound like a probable in your case, but one never knows.

Vit D levels might be checked...

FWIW the geno 1a is harder to treat than 1b, and one may have increased resistance issues; not due to your response per se, but the PI may be less effective on 1a than 1b.

Did you do the fats intake w/ incivek dosing?

The good news is that you found out relatively soon.  You stopped before significant resistant virii generated.  You can wait and when you treat next you'll probably find that the new forms of treatment will be shorter, more efficacious and easier.

I am sorry that it didn't work out....

best,
Willy

[AHNOLD]

Thank you very much for the well wishes and expressions of hope. While I was disappointed with results of treatment, I do feel optimistic about my health and the incoming generation of new treatments!

[AHNOLD]

I'm approximately 6'1 and 225-230 lbs. While I haven't measured it in a while, I'd say I have 15-20% (probably closer to 20%) body fat. In light of this, my Ribavirin dose was 1200 mg per day.

While I was told my blood work showed *some* impacts from the treatment (I never asked for specifics as I always felt great and I was told I was responding swimmingly), I never really felt off, ill, tired, under-the-weather, or any of the side effects discussed in this community. In other words, I wasn't restricted at all from living my life normally.

Given the preponderance of patients that seem to have noticeable side effects, I do think it's odd I didn't seem to have any. Maybe this could (partly) explain why I didn't respond? Again, I'll ask my doctor.

[AHNOLD]

Thank you very much for the well wishes and the insight. That's a very interesting regarding the IL28B gene - I've never head of that before. I assume you know much more than me at this point, but I found an article (http://www.hivandhepatitis.com/2011_conference/easl2011/docs/0404_2010_a.html) saying that Telepravir improves the chances of SVR regardless of IL28B type. Have you heard of this?

Regardless, I'll bring it up with my doctor on Tuesday. Thanks!

[paen53]

Curious to know if your Ribavirin was dosed high enough for your weight.  You mentioned that your hemoglobin hardly budged even with the Incivek....