What causes relapse?

[Ian]

Hi,
I'm a bit unclear to me how, if you're undetected after treatment, that the virus can relapse. Is it that some small bit of the virus was hiding out, lodged in tissue somewhere in the body, which your immune system was unable to reach while on the meds, and now it has becomes dislodged after you're off the medication so it's now able to replicate? I don't quite understand why our immune system is able to kill the virus while we're on the medication, but not able to kill a tiny bit of it once we're off the medication.

Are there factors that can increase chance of relapse, or factors that could reduce the chance? Do factors like age, low initial viral load, and lack of fibrosis help? And if there's some little bits of the virus hiding in my body, could it help if I trained for a marathon or something while Im on the medication, to try to regenerate as many cells as possible and shake loose any bits of virus hiding out in my tissue?

 I'm still 21 days to EOT, but I have been undetected since 4 weeks of treatment with viekira no riba. I'm genotype 1a, 33 years old, 0 fibrosis.

Thanks so much, i'm so grateful for this forum.
Ian

[Lynn K]

When you have the test result virus "not detected" that only means the virus is below the ability of the test to determine it's presence or absence. This is called the LLOQ (lower limit of quantification) of the test.

So it could mean there is no virus or it could mean just a very small quantity could still be in circulation that is why we treat for weeks after we have a "not detected" result.

Our immune system does not kill the virus. If our immune systems could kill the virus we would not have become chronically infected with the virus. The new generation meds prevent the virus from reproducing and with no new copies being made the virus dies off naturally.

On treatment results mean little. The only test that matters is the 12 week post test although a 4 week post test gives a good indication at 98.5% correlation of SVR4 to SVR12.

Things that make us more difficult to cure are having cirrhosis and being prior treatment failures.

Yes having no liver damage does help. There is nothing you can do to cause or prevent relapse except not take your meds as directed even making a small mistake or 2 should have no impact.

I am surprised you are treating with Viekira Pak without Ribavirin as that is not per the prescribing information sheet for genotype 1a that would be correct protocol for GT 1b without cirrhosis. In the Pearl IV clinical trial, the results for GT1a with Viekira Pak and ribavirin was 97% but for Viekira Pak without ribavirin and GT 1a the SVR 12 results were 90.2%

http://depts.washington.edu/hepstudy/presentations/uploads/133/pearl__3d.pdf

Most people are being cured by these new meds but unfortunately it is not 100% certain. Maybe some just have the toughest bugs out there but your odds of cure are good. I know it is hard not to worry what comes 12 weeks after treatment but hang in there.

Best to you
Lynn

[Ian]

Hi,
Lynn, thanks I see now - so it's not the immune system killing it, it's just dying off on it's own. It's odd, why then is weight a factor? I found an article on a study that Dr G Foster did that showed 6 factors associated with relapse (keep in mind this was a study of sovalidi patients ). The factors are dentified below along with a link. Im 6"3' and 205 lbs, so not obese but still over the 75kg. I suppose none of these factors are necessarily causing the relapse, only associated with relapse. Still makes me wonder if i could get under 75 kg if it might improve my odds!

Here are the negative predicting factors Dr Foster identifies:
Liver cirrhosis (odds ratio [OR] 4.3, or more than 4-fold higher risk);
Baseline HCV RNA >800,000 IU/mL (OR 3.9);
Male sex (OR 3.5);
Weight over 75 kg (OR 3.2);
IL28B non-CC (OR 2.;
Prior treatment (OR 2.;
Age over 50 years (OR 1.9
http:/www.hivandhepatitis.com/hcv-treatment/experimental-hcv-drugs/4643-easl-2014-sofosbuvir-works-well-despite-multiple-negative-predictive-factors

 I really appreciate your help.
Ian

[Lynn K]

Yes that data is for Sovaldi with interferon and ribavirin so I would expect Harvoni and Viekira Pak have their own set of predictors.

I do know that ribavirin is weight based and the dose changes at 75kg from 1000 mg to 1200 mg

I don't think they know why weight is a factor is just turns up in the results. I expect they are working on trying to determine the role being heavier plays.

I am wondering why you are not taking ribavirin as you are genotype 1a and per the prescribing information you are supposed to be taking ribavirin with viekira pak.

To me that would seem to be your greatest risk factor for relapse lowering you odds from 97% to 90.2%

Here is some interesting data originally reported at the 65th Annual Meeting of the
American Association for the Study of Liver Diseases Boston, MA Nov 7-11 2014

PEARL-IV Trial: Subgroup Analysis of Genotype 1a-infected Patients Treated With Dasabuvir Plus Ombitasvir/ABT-450/r With or Without Ribavirin

http://www.natap.org/


It has a breakdown of the demographics of the study participants SVR12 rates they are using a BMI of 30 as opposed to 75 kg weight

Also I have this from Abbvie about how Viekira Pak works

https://www.abbvie.com/content/dam/abbviecorp/us/desktop/contentrooms/downloads/ProductFactsheet_ViekiraPak_US.pdf

"Each of VIEKIRA PAK’s direct-acting antivirals has a distinct mechanism of action that work together to attack the virus at three separate stages of the disease lifecycle to inhibit the virus from reproducing."

Best to you
Lynn

[Ian]

Hi,
Thanks Lynn! Yes, I'm not taking the ribavirin. After reading about the pearl 4 testing and learning that even without ribavirin the efficacy was 90% I talked with my Dr about the option of not taking it. I was particularly concerned about the side effects considering some pre-existing conditions it might exacerbate, and also planned to try to have a child very soon. Weighing those considerations against the tradeoff of reducing my chance of cure, we felt that forgoing the ribavirin was the best choice. Also, with my limited understanding  of statistics, I believe that though only 90% of participants in the test achieved a cure that doesn't mean that I personally have only a 90% chance of success. Our individual characteristics are what determine our chance of cure, not the results of a study including many people with various traits and severity of conditions. Looking at the characteristics of the population of the sapphire 4 study, on average the participants are older than me and have worse fibrosis.  I was never able to find specific characteristics of the people in the sapphire 4 who relapsed, but I suspect that they may have had more negative predicting factors than the average for the population. So if my math is right, as long as your characteristics put you near the average of that population, as opposed to being near the more severe difficult to treat segment of the population, your personal likelihood for a cure is higher than that of the entire population.

Anyway, it was a tough decision that I did not take lightly. I'm surprised that the FDA doesn't take into account the individual characteristics of patients. Ribavirin has major side effects for only a marginal increase in efficacy. It seems like they make these sweeping recommendations, not allowing the dr to consider what's best for the individual patient or risk lawsuit. Of course, for a huge federal agency I suppose they can't feasibly get that granular. At a certain point it's up to the dr to look at the individual patient and decide if it's okay to diverge from the FDA recommendations, and from what I understand they actually do this all the time.
Ian

[Lynn K]

I believe the recommendation is if you can't or do not wish to take ribavirin that you should have a different treatment but of course then insurance coverage becomes an issue. I am certain the FDA looks at individual characteristics but they are providing what appears to be the best recommendation of cure and the information on why they made the determination why it is better for gt 1a to take with ribavirin is in the reports.

That being said they did have some comments in the link I sent that the effect of not taking ribavirin was less pronounced for women than men and as you observed statistics can give an incomplete picture of how that all will play out in your individual circumstances. I suppose yes if you have fewer of the negative indicators your odds are better the 90% which is the overall. However clinical trial date does tend to be a little higher than what is found once a medication is released to the public.

As your question was what causes relapse that was why I was wondering why you were not taking the riba

Anyway thanks for clearing up about the ribavirin I can see why that would be considered for you.

Best of luck and happiest of holidays
Lynn