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

[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