VL showing 715 andTMA Pos at Week 24 (after being TMA Neg since wk 4)

[SkipinCA]

Am 60 yr. old, geno 2b, VL was 2,387,610 at beginning of 24-week treatment in July ’07.  Did INT 180mcg, 1200 Riba until 10/2, then 1000 Riba daily for rest of tx.  Results of tx had been ideal from the start – was UND (HCV RNA <615) and TMA negative at 4 weeks (8/29) and continued same at weeks 8, 12, and 16.  Then, at week 20, I tested HCV RNA<615 and TMA positive, retested at week 22 and the HCV RNA is at 715, TMA positive.  I did my last injection (of 24) last Friday and am on my last week of riba.  I have an appointment with my doctor today to discuss.  I am having another fasting blood test this week.  Has anyone had a similar experience, and do these recent results mean the tx is not working after all and that I should stop tx and wait for a better treatment down the road?  I have one refill of 4 injections of INT left I could use, plus enough riba for another 4 weeks.  Would an additional 4 weeks tx with an increased dose of riba (1200-1400 daily) make a difference with the results I’m getting right now?  I’m sure my Dr. and I will discuss this today, but I wanted to have an idea of what others have to say.  Thanks for your help! Skip

[SkipinCA]

Thanks for all your help.  I saw my doc today and we discussed what she said definitely appears to be a breakthrough in treatment that occurred somewhere between week 16 and 20.  Said it is atypical for this to happen in a case like mine where my results have been so good up through week 18.  Background:  Biopsy showed no fibrosis etc., no liver damage at beginning of treatment, did the whole course with INT 180mcg/wk and started out on 1200 riba, switching to 1000 riba at week 16 due to low CBC issues.  I was not weight-based (am 6'4", 238 at start of treatment, am at 215 now), and there is an earlier discussion about the fact that we switched me to 1000 riba (my doc's reasons were very persuasive) and the pros and cons of that.  I suppose that reduced dose may be a factor, but the fact of the TMA positives may have happened regardless.  Something I'll never know, I guess.  Better to know now than live with false hope and have it happen later.  We are doing a followup HCV RNA test and a genotype test since apparently the genotype test only shows a dominant strain and if I have two strains of HCV then we may have just treated 2b and not the other.   The options will be that I will stop the current treatment and do a new, longer treatment regimen or wait  for awhile for new possibile tx down the road.  Evidently, there are many trials out there involving shortened treatment regimens.  My CBCs and other tests have been good throughout tx, and have had very little problems with sides. Meanwhile, until the tests come back, I'm continuing the next 2-4 weeks with INT180 and riba 1200.  Will meet my doc again at that time.
Jim, I'll print and read the studies, and I'll check out the Clinical Care options, Mike.  You all are speaking in a language I barely know yet, but I appreciate the input.   skip

[jmjm530]

Pure conjecture, but it may not be coincidence that your breakthrough coincided with a reduction in ribavirin. The trend among some of the better docs seems to be weight-based even for geno 2's, and weight-based in your case would have been 1400 mg/day. Then, at week 16, your dose was further reduced to 1000, way under weight based. In spite of a recent study that suggests OK to reduce riba in geno 2's after UND, seems like too much of a reduction here, which also begs the question why didn't your doc suggest Procrit (epo) instead?

At this point, if you had significant liver damage, I could see upping the riba to 1400 in concert with epo and continuing on another 24 weeks with frequent VL testing. But given no fibrosis, probably better just to stop at 24 and wait for better drugs.

That said, assuming you've been tolerating treatment well, a compromise might be to convince your doc to bring you up to weight-based now (1400mg/day) and start you on Procrit at the same time while monitoring VL every two weeks. If you get UND within 4 weeks, then continue to run out the balance of the 12 weeks as long as you remain UND. If you breakthrough again, then stop. I have absolutely no study data related to what I've suggested, just an opinion, and the kind of conversation I might have with my doctor if in your position.

-- Jim

[willing]

got to congratulate you on keeping such a great attitude! The Dr's question about the multiple genos is interesting - this seems rare but does happen - here's a recently published case:
http://www.ncbi.nlm.nih.gov/pubmed/17631045

Since your last pcr got up to 715 there should be enoug RNA to test for genotype.

You might also want to look at  a recent study on weight-based dosing and duration for 2s:
http://www.ncbi.nlm.nih.gov/pubmed/17894303
note that neither weight-based rbv nor extension to 48 made much of a difference in svr rates (and this was a big patient group).

However, the ifn was weight-based ifn-alpha-2b at 1.5 microg/kg/week (schering) rather than the one-size fits (roche). Did you use pegasys?

[jmjm530]

The think you want to keep in mind when reading a study like this, is how the study group matches up to your stats. My guess is that there weren't many 238 pound men in those studies meaning a much greater disparity between the riba dose Skip was treating, given his weight -- and at least for me, the conincidental breakthough coinciding with the riba reduction must be given some consideration in an individual case.

Bottom line is that an increase in riba either will, or will not have an effect on Skip's viral load. If it does, then it seems reasonable to go ahead as I suggested with the compromise plan since 24 weeks has already been invested, and assuming no significant side effects. Just an option to consider. Stopping is certainly another option.

-- Jim

[willing]

jim -  can't get to the study content (argh!) which presumably includes detailed patient demographics, but note that the abstract makes a point of indicating 1400mg/day was found  appropriate for those in Skip's 108kg weight group with geno 1s but they nevertheless observed no benefit in more rbv for 2/3s.

skip - just to clarify my last comment above, your references to 180mg IFN sounds like pegasys. I'm not sure what evidence there is for this but have read that the Schering weight-based dosing may be more effective than roche's one-size-fits all above a certain weight

[jmjm530]

Willing's "Pegasys" comment is germane, but it should also be pointed out that the study language states that weight-based ribavirin "is more effective" even with genotype 2's and uses the word "adequate" when referring to weight based.

In reference to the same study, Science Daily makes the following point specific to "higher weight" patients like Skip:

For patients infected with genotype 2 or 3, a 24 week course of treatment with flat dose RBV + PEG-IFN was as effective as the standard 48-week course, with better tolerability, and in the overall study population flat dosing of ribavirin was as effective as weight-based ribavirin. However, within the flat-dose cohort of patients with genotypes 2 and 3, sustained response rates showed a slight decline in the higher weight patients given flat-dosed ribavirin.

http://www.sciencedaily.com/releases/2007/12/071227183754.htm