Dropping out of Tx at 8 weeks...

[Virusbuster]

I just got my 7th week VL result: 2.6 million. Given that I started with 13.7 million, a 0.72 drop. Well below the 1 log that I had agreed with my doc as a stopcriterion. Hence, I stop, right here, right now. It was a horrible 8 weeks, and I can only say I'm happy the result is black or white (albeit black in this case) and not grey.

Hopefully, I'll be me old self again soon. And even more hopefully, my liver will last until the new meds come out.

Thank you guys for all the support you have given me the past weeks. I'll try to reciprocate.

VB

[Virusbuster]

Yes, I want to keep a close eye on my liver, and a biopsy is a good way to do that. In fact, I had pleaded to have one (or at least another fibroscan) just before starting Tx. My doc was in a hurry to start, because of my HIV that was on the rise again. One of the reasons to start Tx asap was to have the interferon give a final blow to my HIV. That worked btw, my HIV became UND after 2 weeks of Tx. So my attempted Tx has certainly not been in vain, even though it didn't seem to work for my HCV.

In other words, the precise state of my liver would not have influenced the decision to start Tx.

Anyway, when I'll come back from my vacation we'll discuss the new situation. That will include liver monitoring and possible IR.

Tonight though, I'll pack my suitcase so that tomorrow I can catch a plane to Malaysia. I only worry a little bit that I may get ill, due to my low WBC. My doc already gave me powerful antibiotics, just in case I get diarrhea. However, I hope my immune system will bounce back quickly now the flow in INF is cut off. ;-)

[jmjm530]

As someone who as championed earlier stop rules I found myself in an odd position here arguing the opposite, but only because of your stage and co-infected status. While certainly not a probability, but with five weeks to go until week 12 there was a reasonable *possibility* of that two-log drop IMO, perhaps if the Peg was changed or increased even. Forget about the 5%, but I also found the 17% figure quite low when compared against the broader concept of co-infected patients achieving smilar SVR rates to those not co-infected, but frankly have not researched that any further. Don't have the figures handy how non-coinfected EVRs do with 72 weeks but my recollection is that it's higher than 17% extracted from much larger studies.

In any event, good luck moving forward and thanks for being such a good sport in terms of how you reacted to what might have been construed criticism of you decision. It certainly wasn't an easy one and while I might not agree stopping five week short of the week 12 results,  in the end you probably are right that the week 12 results in all probability won't cut it. Maybe this is a case where the patient is the realist and the docs the dreamers :) Have you thought about getting a biopsy now?

-- Jim

[charm27]

I personally think you made the right decision....There are many people here that have been a stage 3 for a LONG time...Many of us also are waiting for the new drugs to retreat. I wish you ALL the best and hope you are able to put this all in perspective.
Have a beautiful vacay and again I wish you good health and the best of luck.

Charmm27

[Virusbuster]

He only had a .23 log drop at 4 wks and I had a little over a 1 log at 6 wks"

I have to correct you there, Trinity. Indeed, my 4 week drop was 0.23 log. But my 7 week drop was 0.72 log. I didn't even make it to 1 log in those 7 weeks...

--------------------------------------------------------------------------------------------------------------------

Trinity, I misread your post, sorry. You were talking about yourself (1 log at 6 weeks), and I read it as if you were talking about me.

VB

[Virusbuster]

Still puzzling why the numbers in that article you brought in are so different from those in my protocol. And it's a big difference, not a small one. Nevertheless, thanks for bringing it up.

Yes, my "top notch staff" (I'll tell them next time I see them!) were not happy with my proposal. Nor would I have been if I had been in their shoes. Partly, because I'm 'polluting'  treatement data, and a protocol wouldn't be a protocol if you keep diverting from it. That's why I didn't make up the stopcriterion myself. I let my doc define what she considered a test result that would be hopeful on beforehand, as well as what would she consider hopeless. She stated that > 2 log drop she'd consider to be hopefull, and < 1 log as hopeless. That was what she discussed in the team, and it was agreed to that. My 0.72 log drop is clearly in the "hopeless" range as far as they are concerned.

Now, whether IF I would have reached 2 logs at 12 weeks, my chance of SVR would be 5% or 17% is an interesting question. But it is a) questionable if I would have reached 2 logs and b) even 17% is a lousy chance.

I hope to be able to enroll a trail for the new drugs for co-infected patients soon. Meanwhile, I'll be as nice to my liver as possible.

[jmjm530]

Trinity: It appears VB is under the care of a top notch staff even though he had to debate ending early and they did see the logic.
-----------
Honestly don't see your point or what you've been driving at. It's quite clear from his post earlier in the thread that his treatment team strongly suggested continuing on to week 12. That's all I'm suggesting. Are you saying you don't agree with his "top notch staff"? As to the SVR rates of co-infected, I'm not making anything up just posting study statistics as you are.

I certainly support VirusBuster's decision but was simply playing a bit of devil's advocate to make sure he has as much input as possible. The 5% number was just for those who failed to make the two-log drop and I was simply saying that he still might make it, just as I'm sure his "top-notch" team might have argued.

-- Jim

-- Jim

[Trish77]

Your CD4 count is a signficant factor. It's already dropped a signficant amount and you would have had a ways to go to get through treatment.  Not sure your CD4 count would have held out. My CD4 count dropped to 109 at it's lowest before they yanked me off treatment.    

It's a tough decision you're making and sounds like you're doing it with eyes wide open.   Some trials will take you if you're six months off of treatment so hopefully you won't have too long to wait for a good trial to come along.  In the meantime, keep investigating IR and whatever other reasons you may not have responded to treatment.  And, please, keep a good eye on your liver damage.

You just may have to go at this again without new drugs sooner than later.  If you do, I would suggest you investigate planning to incorporate neupogen for your white counts and procrit for your hemoglobin to counteract the impact that the interferon and the ribavirin have on both respectively.   I would suggest you look into both of them and see if it makes sense to include them as part of your treatment plan.  Many people take them to allow them to adhere to the treatment and reduce the adverse effects at the same time.

Good luck to you.

Trish

[jankar]

As someone who stopped treatment at 24 weeks with geno 1b, I am firmly convinced that we do have to take a long term approach to our treatment options.  There are new drugs around the corner and I think 72 weeks in the current circumstances is far too long for some of us to have to treat.  I had been monitoring treatment options for 7 years before I decided to treat.

Good decision, I think. The current treatment times are so long and potentially toxic.  I think practitioners do not like to work outside SOC for their own safety.  Research clearly indicates a greater range of options than current SOC.

Have a great holiday.

[Trinity4]

Jim,

We're certainly no experts on HIV/HCV co-infection.  Pearlman specializes in co-infection too.  When I visited him in October, he gave me a handbook he had written for all his patients. It deals with many issues including co-infection.  Even though it's not a study, there are specifics.  This is from the chapter on co-infection

Patients with HIV are treated with the same medications as HIV negative patients with hepatitis C (interferon and ribavirin).  The response rates are lower in co-infected patients, about 14-20% for genotype 1 and about 40-50% for genotypes 2 and 3.  Often, a liver biopsy is obtained to help decide how urgently treatment should be considered.  Since HCV progresses faster in co-infected patients, your health care provider may recommend treatment at an earlier time than in HIV negative patients.  Medicines for HCV do not work as well in patients with low CD4 counts.  All persons co-infected with HCV and HIV should be seen by physicians knowledgeable about both HCV and HIV.

It appears VB is under the care of a top notch staff even though he had to debate ending early and they did see the logic.

VB has low CD4 counts so an additional 5 weeks on the medication may not prove beneficial towards a 2 log drop or even UND at any point.

[jmjm530]

Sorry, my previous post was transposed incorrectly. Should read:

62% SVR rate if <600 IU/ml by week 12
17% SVR rate if greater than 2 log drop by week 12 but still detectible.

[jmjm530]

OK. The figures I have are for HCV/HIV Coinfected doing 72 weeks are:

62% SVR rate if  2 log drop by week 12 but still detectible.

My point is that Trinity had a somewhat similar response and I believe ended up with a two-log drop by week 12, so maybe you would as well.

72-week Extended Treatment

R. Chung and colleagues (abstract 103LB) reported the latest data from the SLAM-C trial (ACTG A5178), designed to look at interferon maintenance therapy and extended combination therapy in HIV/HCV coinfected patients (standard duration for coinfected patients is 48 weeks regardless of genotype).  Initially, 329 coinfected individuals were treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin for 12 weeks.  At that point, participants who did not achieve early virological response (EVR) – at least a 2-log drop in HCV RNA – stopped ribavirin and continued on pegylated interferon alone (as reported at last year’s Retrovirus conference, maintenance therapy essentially demonstrated no benefit).

Of the 183 participants who achieved EVR, 169 opted to continue the combination regimen for a total duration of 72 weeks (data were available for 146); 78% had HCV genotypes 1 or 4, 29% had prior interferon experience, and 9% had cirrhosis.  Overall, 51% of patients who achieved EVR went on to achieve sustained virological response (SVR) 24 weeks after completing therapy.  But patients who achieved complete EVR – undetectable HCV RNA (< 600 IU/mL) at week 12 – were almost four times as likely to achieve SVR (62%) than partial early responders who had a 2-log drop but still detectable HCV viral load (17%).  Overall, African-Americans had a lower SVR rate than non-black patients (38% vs. 57%).  Among complete early responders, however, SVR rates no longer differed significantly according to race (65% for whites vs.  54% for blacks).  About one-third of study participants stopped treatment before 72 weeks, with a majority of early discontinuations and dose reductions occurring during the final 24 weeks.  The researchers concluded that patients who achieve complete EVR “do very well,” whereas those with partial EVR have “very limited responses.”


http://www.hcvadvocate.org/news/newsLetter/2009/advocate0309.html#1

[Virusbuster]

"bottom of page 6 second paragraph from the bottom says 2%, right from Roch/Pegasy
http://www.rocheusa.com/products/copegus/pi.pdf  "

Isn't that for a 48 week treatment? I would go for 72 weeks, and I expect the success rate to be higher then, indeed.

"New drugs right around the corner are looking better every study I read."

Indeed, that's what I look out for now. I hope not to have to wait two years. But instead, to be able to participate in a trail of HIV-HCV co-infected. The trails for treatement-native patients are coming to a conclusion. Hence, soon they will want to move on to people like me. ;-)

[Virusbuster]

"He only had a .23 log drop at 4 wks and I had a little over a 1 log at 6 wks"

I have to correct you there, Trinity. Indeed, my 4 week drop was 0.23 log. But my 7 week drop was 0.72 log. I didn't even make it to 1 log in those 7 weeks...

What I did manage in those seven weeks was
- Getting close to anemic (HB from 14.7 to 10.9)
- WBC falling through the bottom (from 5000 downto 2300)
- loosing 240 CD4 (from 550 downto 310)
- loosing 2 kg of my already not so much 69 kg (@ 1.89 m)
- getting a real bad depression
- fatigue and/or chills half of the days
- and of course the loss of appetite, rash, nausea, anxiety, mood swings, concentration loss, no sex drive, ... (did I overlook anything?)

No, I am sure I don't want to hold out another 5 weeks with such a bad result now. Not to mention ruin my vacation. (Although, I was fully prepared to sacrifice that if I had any belief I stood a reasonable chance. Operative word here: reasonable)

[apache1]

Tough decision... sorry you didn't respond better...

Wonder what causes such a difference in studies of svr rates for co-infected not getting a 2 log drop by 12th wk. ?

bottom of page 6 second paragraph from the bottom says 2%, right from Roch/Pegasy
http://www.rocheusa.com/products/copegus/pi.pdf

New drugs right around the corner are looking better every study I read.

good luck,
apache

[Virusbuster]

"this suggests sijmilar svr rates for coinfected (40%) geno 1's
http://www.hivandhepatitis.com/hiv_hcv_co_inf/2007/101907_a.html "

The only reference to 40% SVR I find in this article is here:

"At this time, up to 40% of coinfected patients can achieve SVR with combination pegylated interferon plus ribavirin therapy."

However in that very same article I also read:

"Early virological response (EVR) assessed after 12 weeks of anti-HCV therapy is an important indicator of virological failure. The failure to achieve an undetectable HCV RNA level or reductions in HCV RNA of at least 2 log10 by 12 weeks has a negative predictive value of 98-100% for treatment failure [32]."

According to my protocol, I, having HIV, being geno 1, started out with a 29% chance of SVR. Failing to reach a 2 log drop at week 4 made my chance of SVR drop to 10%. Failing to reach this by week 12 would make it drop to less than 5%. (note, when treated 72 weeks!)

I'm treated by one of the major university hospitals in the Netherlands. It has a large HIV departement. I may sincerely hope they have done their homework when defining the protocol (which is labelled as version 1.8, dated 8 june 2008). There is a list of references to 12 scientific publications included, mostly dealing with HIV-HCV co-infection.

[jmjm530]

Yes, but the SVR rates are similar with co-infected, so not sure that advisement is correct. Also, very high viral load and high have same results. I do hear you that it isn't apples and apples but only suggesting he wait until week 12 to see if a two-log drop can be achieved. It's only a few more weeks. Have a feeling you would wait :)

-- Jim

[Trinity4]

VB's viral load was a lot higher than mine starting out.  He was 13,000,000 and I was 1,300,000.  He only had a .23 log drop at 4 wks and I had a little over a 1 log at 6 wks.  My biggest drop occurred between 6 wks and 14 - 15 wks but a big factor here is he is co-infected and his doctors advised him the HIV drugs can reduce the effectiveness of the HCV drugs.  

[jmjm530]

Virusbuster: Also, I don't have faith that when it takes 7 weeks to achieve a 0.7 log drop, in the remaining 5 weeks it will suddenly drop way below 2 logs.

Trinity: I barely got a one long drop at 6 wks and still had not cleared at 12 wks but did sometime around 14 wks.
----------------------

Trinity had a similar response to yours and did clear around week 14, so maybe giving it another 3-4 weeks is a reasonable choice as your doctor probably argued -- that is if you're willing to accept a 30% chance of SVR with 72 weeks of total treatment, assuming you follow Trinity's pattern.  In your shoes I probably would, but of course I'm not.

-- Jim

[Virusbuster]

"Is the 5% figure with 48 or 72 weeks?"

72 weeks for genotype 1, co-infected with HIV.

"Do you have any study back up?"

The < 5% chance if at 12 weeks there's a < 2 log drop comes straight from my treatement protocol. It refers to the Apricot Trial of HIV-HCV co-infection, abstract at CROI 2003. Even though I haven't seen the publication with my own eyes, a < 5% SVR chance seems to me like a reasonable threshold to give up treatment..

"As you know, fibrosis progression is greater if you're co-infected so personally, given you're a stage 3,  I'd think twice about stopping now unless you can verify those figures. Ploughing on until week 12 might make some sense as your doc suggests."

I have no doubt about the protocol used. I think it's pretty standard, actually. Also, I don't have faith that when it takes 7 weeks to achieve a 0.7 log drop, in the remaining 5 weeks it will suddenly drop way below 2 logs. Note, just making it to 2 log isn't good enough. I'm not willing to put myself through 60 more weeks for a 5% chance of SVR. It should drop more than 2 log. And I just don't see that happening.

I know my liver isn't into that good a state. It will be monitored closely in the time to come. Hopefully, the fact that my HIV is now UND will make the detoriation less. But for now, it's the end if this battle of my little private war. And I'm gonna enjoy my vacation as much as I can.

[jmjm530]

Not sure if that's good or bad news. Anyway, Fibroscan said stage 3 and coinfected individuals progress faster.

[portann]

VB had no 'proper' biopsy, as I believe he said.

[jmjm530]

this suggests sijmilar svr rates for coinfected (40%) geno 1's
http://www.hivandhepatitis.com/hiv_hcv_co_inf/2007/101907_a.html

I'd really think twice about stopping  before week 12 given: (1) coinfectrion: (3) stage 3:

[Trinity4]

Sorry you did not have the viral load drop you were looking for.  I barely got a one long drop at 6 wks and still had not cleared at 12 wks but did sometime around 14 wks.  You would have a greater challenge with co-infection though.  Hgb went from 12.6 to 11.2 in 3 wks but never went much below that and it's back up to 11.5 - 12 after 57 wks.  WBC started low and continued on a downward trend until Neupogen was prescribed.
I agree it was the right decision to stop and you can plan new strategies now.  

Best of Luck to you,
Trinity  

[jmjm530]

http://www.hivandhepatitis.com/hep_c/news/2009/042109_a.html

Also, a newer study suggests that tx possibly can reduce fibrosis rregression even if no svr