Interferon dose redux and viral load test problem

[SukiDiMota]

This is my first post. I am a 54 year old woman , GT 1A, S3, in my 37th week of treatment w PegIntron 2-b & Ribavirin.

At the start of treatment my  VL dropped from 900K to 81K in two weeks, then 1.5 K at the end of 4 wks. However at 12 wks I was still detectable at <615 . I cleared somewhere between 12 and 19 wks so I am considered a slow responder. I am still undetectable.  At wk 19 they cut the riba from 1000mg to 800 mg due to anemia. At wk 26, after a fever and gastrointestinal illness that lasted 13 days, my interferon was reduced from 96 to 64mcg . My weight was 63.5kg at that time and is now 60 ( started at 71kg) . After becoming dissatisfied with the treatment I received I got an informal (unpaid) opinion from a highly experienced hepatologist, who I saw once when I was at S0-1 five years ago.  He told me that my Nor CA HMO should never have reduced the riba, that I should be  but should have put me on EPO. He also said w S3 fibrosis at biopsy 2 yrs ago I should be treated for AT LEAST 72 weeks, if not 96. I stood up on my hind legs with my HMO and finally at week 32 they put me on low dose epo and changed their policy ( I seem to have ruffled some feathers in the process). My HGB is back up from 9 to 10 , my ANCs are around 1000. I bumped the riba dose back up  but  with the added load the interferon is doing me in even at 64 mcg. Fever, headache, nausea, body ache, insomnia and episodes of twitching. If I maintain the current dose trajectory, by the end of week 72 I will have a 88% or the IFN originally prescribed, and 102% of the riba (figures adjusted for weight loss). Though I have a little more energy since the EPO took hold I am getting worse sides now from the interferon. From what I can glean from my reading it behooves me to keep the riba dose up which I am doing.  Trouble is I am not sure I will be able tolerate the IFN for another 35 weeks. I am currently at 96% of my weight adjusted dose, which I believe was too low to start with at 1.35mcg /kg (I am thinking that may be why it took so long to clear after the big first and second phase drops). If I maintain my current IFN dose, at the end of 72 weeks I will be at 87% of the weight adjusted original dose (&102% of the Riba, or 14.2mg/kg). I don't see a lot of information on interferon redux later in treatment, only the HivandHepatitis.com article that said that IFN dose redux to .6mcg/kg  after Wk 12 did not affect SVR. Does reasearch support this assessment?  I use the vials so dose tailoring is not a problem, but I just don't see good info on late Tx IFN redux. According to the mfg's instructions I can, at my current weight of 133 lbs, reduce IFN to 50 mcg for the first  redux and down to 30 if  a 2nd is needed. I am at the very top of the weight range and I am uncomfortable with these numbers, esp the second one.  Anyone one have any substantive information on late-treatment IFN redux and relapse? I may feel better if I reduce the Riba again ( I've now lost 11kg) , but from the reading I have done I am reluctant to do that.

Re VL : My lab results read <615 at 12 wks and then "NEG" at wk 19. I have inquired of my Tx Dr twice now about the threshold of the test they are using to determine NEG  since wk 19, and he tells me its either NEG or its not. I have never heard of a test that didn't have a detection threshold for VL. Its also  inconsistent with the  fact that the supervising GI Dr told me I should have gotten a more sensitive test from early in treatment and that I would starting last lab. I am concerned that they are stonewalling, not giving me info out of fear I will use it to sue them. When I told them of the second opinion  I received a total of three emails and a phone call, within 90 minutes, from two drs spouting the party line " we want you to have the best care, blah, blah, and offering the EPO and 72 wks of Tx.  Any info or suggestions esp on the interferon issue would be most appreciated. I am about to requisition my medical records and have a look for myself so I can see what type of VL test is being done. I do not have confidence in my doctors, they lack experience. I am self employed and am a Cobra refugee and basically a captive of my HMO.

Thanks,
Sukidimota

[jepperone]

If you are up to reading about a more sensitive pcr test here is a link that may be of interest.

jep

http://www.medhelp.org/posts/Hepatitis-C/more-sensitive-pcr/show/383166

[epiphiny]

Further to my comment about Qualitive vs Quantitive, I just searched MH for any discussion regarding this and there are plenty to choose from:

http://www.medhelp.org/forums/search/75?query=qualitive

[epiphiny]

Someone correct me if I am wrong but I was of the understanding that the qualatitive test (pos or neg) is actually more sensitive than a quantative test?  That could explain why they are saying it's either pos or neg.

[SukiDiMota]

Thanks for your reply. The research I've read seems to indicate the reverse. That Riba is important in preventing relapse and the interferon dose reductions after the virus is cleared ( if it indeed is/was!) have negligible effect as long as they are about .6 mcg/kg. Right now I am at about 1.0ncg but not tolerating it too well.

[SukiDiMota]

Thanks Trish,
I think they under dosed me on the IFN to begin with- Scherring-Ploughs recommendations seem lower than what is used for studies.  If keep my dose at 1. mcg/kg then I will finish at 86.4% of the original dose (adjusted for the weight loss) or 72.8% if I use the higher 1.5 mcg/kg. My biggest question is if I have really cleared or if the virus is still hanging on at levels the test is not picking up.
-SukiDi

[SukiDiMota]

Hi, thanks for your reply. I am back on the full dose or Riba (even thought my weight has dropped)  but I am barely able to tolerate the reduced dose of IFN ( about 1.0 mcg/kg).

Thanks for the support. I feel like I am a nuisance to the treating internist, so I plan to go back to the GI dr for an explanation of what is going on and to ask for a more sensitive test. if I don't get satisfactory answers i will consult with someone  locally, but outside my HMO plan. My old hepatologist ( 2300 miles away) will probably refer me to one of his VA colleagues.

[SukiDiMota]

Thanks merryBe,

I never did find out what the GI illness was. My white counts had spiked 250% so they put me on Ciproflaxin, which made probably made the GI problem worse. I quit taking them after eight days but had problems for another five or six until I started taking immodium. I don't get these kinds of problems very often so I have never taken it and my GP did not suggest it when I went in during the middle of the antibiotic course! It wasn't the flu- no coughing ( other than the regular Riba cough) no sneezing, no sore throat or runny nose. I had been having a lot of  stabbing pain in one ear and there was concern that I had an inner ear infection. My WBC is back down and low at 2.0, I have a little more energy with a 10% rise in Hemo but the IFN is still kicking my behind. Yes they did reduce the dose in order to save on EPO they don't prescribe it until HGB reaches 9. Even after it was prescribed, the internist made a point of  telling me that its use did not improve SVR rates. Sure it does, if it makes the difference between quitting treatment and staying on it!

The hepatologist I saw was outside of my HMO and is 2300 miles away. I may have him refer me to a colleague of his who works with UCSF and the SF VA hospital. I am going to give my GI Dr another try with my questions,  as my treating internist is not giving me the answers. As the virus hung on at low levels after the initial drop I don't know if I really cleared. I indicated this to the internist who  replied that  they DO know when I cleared the virus (between week 12 and 19). Twice now I have asked about the sensativity of the test and gotten the same answer- "either its positive or negative".  The GI Dr had told me they were going to start using a more sensitive test on the last lab, that I should have gotten it earlier.  I am not sure this was done. There were problems with the requistion and the internist may have ordered the same (old) test in error, for the second time!

My 3 yrs of CA Cobra expired but I was able to continue at a rate  that is a third higher , but at least I have insurance. My  drug and lab costs are 2-3 times higher and I am only able to work part time.  They will treat for 72 wks, but since they screwed up my riba and IFN prescriptions I will have another 2-3 wks worth of those meds and could conceivably extend another 6-8 weeks by borrowing. I don't know if I can go that long however, the IFN is really doing me in, even at the reduced dose. Hence my question about late-treatment dose redux.  That would take me into Nov and probably six months from Teleprivir approval/availability. I may be chirrotic by now, my eyeballs got  yellowish the month I started treatment.
-SukiDi

[merryBe]

peg has been weight based from the get go. As is Riba by most docs.
Not tailoring it to weight is the exception now, not the rule, and NOT what the manufacturer suggests.
the CD that comes with the new patient pegasus kit explains why we express the excess to get down to the dosage mark on the syringe our docs have told us to use.

Only the obese or large men take the full 180...if you are slender you use only part of each shot.
I realize lots of folks got the full 180 regardless of weight, but this can really backfire on the slender. It's totally nuclear, and basically it causes the small to double dose, which is not wisdom.

[Trish77]

I haven't heard of tailoring IFN to weight the way you're doing.  I've heard of it with riba but not with IFN.  Any sources you can include, I'd be interested to read those.

Having said that, I think you're doing a pretty fine job of advocating for yourself.  I agree with you on keeping that riba dose up there and getting on the Epo.  Nice job.  With regards to the IFN, I'm looking at your side effects and wonder what you're doing to treat those.  Insomnia can be a b*tch and wonder what you're taking to treat that.  It would be preferable to maintain dosage and not reduce if possible and treat the side effects first and foremost.  

Keep fighting for a higher sensitivity PCR.  One at <615 is dark ages on treatment these days in Canada/US and would give me cause to wonder about the experience level of any doctor using that.

What's very concerning is that you are a good advocate for yourself but what about the other people being treated for Hep C by this bunch of clowns?  Always bothers me to read stuff like that.

As for your major question on the impacts of reducing INF dosage later in treatment, all I have is anecdotal comments and no hard evidence at my fingertips at the moment.  There is a reason that ribavirin and INF on their own are not effective as monotherapies and why the synergistic effect of both of them together is key.  I'd be careful about reducing the INF so low so as to reduce the effectiveness of the overall combination.  I would focus on addressing your side effects wherever possible.  Perhaps there will be others who can produce some studies on this.

Good luck.

Trish

[desrt]

It's my understanding that maintaining full dose riba is less important during the later part of tx. If reducing riba helps you stay on a higher dose of IFN, I'd go with the riba reduction. A qualitative viral load test will give a simple detected/undetected without  a sensitivity being given, as you would have on a quantitative PCR.

[jepperone]

Refugee,

Sorry to hear of your dilemma and what a dilemma it is because you are the one that is going to pay the price for it in the long run. I would go back up to the original starting dosages of both the inf and riba now that you have the epo on board and “demand” that a lower sensitivity pcr down to <5 or lower at this point to find out exactly where you are at with the vl. Playing catch up is very hard with this virus because of its adaptive nature to the immune system and evasive maneuvers of the virus. It is a shame that treating doctors know so very little in the way of treating hepc. At this point there is a couple of things you may be able to do if you are still getting the original prescriptions, one, get all your past blood work to this point, two, as said above get a lower sensitivity pcr down to <5, three, get a “new” completed blood count. You have them on the ropes a little at this point so use it to your advantage. It seems like you have a good handle on what has been done so far and you may be able to help your self going forward.

Jep

[merryBe]

sorry to hear your troubles...sounds like some of mine..

what was your gastro illness? Did you ever find out?
I had a similar profile, rebound, internal infection, etc...
I'd rather have a tad more info before answering...what symptoms what test and what treatment did you have for the infection....are you prepared for another year on tx and can you afford the procrit when your cobra runs out. You are likely to need the procrit through the duration.
>615 test is a cheap current test that really doesn't tell patients what they most need to hear...that they are beating this thing.
Any reason you can't go back to your former hepatologist?
At your weight and condition you need someone who pays attention.
At the very least do what you are doing, read, learn ask lots of questions...

You are doing right by demanding your records....if they even only think another doctor may be watching them they will do a better job of giving you state of the art care.
There are of course times when riba reduction is in the patients best interest, but that has to do with all the blood work, not just HGB. Sounds like they may have lowered doses just to spare the insurance the EPO expense.
If you do lose your cobra you can request assistance from the manufacturer.

I stayed on my treatment because I reasoned that my rebound may have been due to my infection (which turned out to be a bad gall bladder causing sepsis) and that my VL may respond once it was removed, which it was at week 17...after which I promptly went UND. However absent any extenuating circumstances like these, the stats are not very good for succeeding in treatment. That's why I ask if you know the infection source and if it has been resolved. Some folks do SVR with extended tx, so I would never discourage anyone from trying,...it didn't work for me....and it is a hard choice.
mb