Which medicine after sebivo

My dad is suffering from hep B and was on sebivo for past 2.5 yrs.
Now this medicine is not responding and doctor has suggested to use another one.
Which is the best medicine to use after sebivo and what are the long term effects of same.

[anjan8808]

Hi Pritesh I am using Sebivo from last 6 months, may I know what is your dad's HBV DNA count (recent reading)  

[Pritesh1357]

He has just recent got a value of 736.

[Pritesh1357]

Also test results show that there is resistance for Lamivudine and Entecavir and possible resistance for Tenofovir and Adefovir what does this suggest?
Can any one point it out

[stevenNYer]

It sounds like your father was taking one antiviral at a time, developed resistance, then moved to the next, then resistance, then to the next, etc.  This the the horrible model to what's called "cross-resistance".  See this thread for more info:

http://www.medhelp.org/posts/Hepatitis-B/Antiviral-cross-restance-chart/show/519565

Treating a multi-resistance HBV patient will be challenging.  You may have to rely on long term interferon or  HBIGshots, both of which can be very expensive.

[Pritesh1357]

He directly started from Telbivudine and as per the link you have provided he can go to Tenofovir or Adefovir.
Which is the best to go for?
What is the best model to follow according to you.

[Frade]

Tenofovir (TDF) should be the right choice, as it has a better profile of resistance than Adefovir (ADV).

TDF is a well know drug commonly used for HIV treatment. And its indication for HCV infection is more recent than ADV. Even though there is lesser experience with TDF, there is no resistance documented after 3 years of treatment. With ADV, there is documented resistance.

Four years ago, your father would have passed from Telbivudine to Adefovir right away. Nowadays, TDF is theoretically a better option on long term treatment. However, it is up to your fathers' doctor to choose the right treatment, as it also depends on other factors.

[Pritesh1357]

Thanks Frade,

Just had a doubt that what after TDF as if there is resistance to this then there is hardly any option left unless new research are successful.

[stevenNYer]

Now you see why resistance is such a serious issue.  If there is already resistance to Telbivudine and then develop resistance to TDF, there is no new bailout class of antivirals on the horizon.  If this case, if the hepatitis becomes very severe, then you have to talk to the doctor about interferon and HBIG shots.

For your father case, I think a add-on strategy is better than a straight switch.  Stay on Telbivudine and add on TDF.  This is said to be more effective in managing resistance.  Talk to the doctor.  And get a second opinion, since doing Telbivudine monotherapy for over 2 years wasn't a wise plan to begin with.   Now after the facts, you lost Entecavir.  Entecavir has only like a 2% resistance rate after 5 years.

[Frade]

In fact, it is not expected that new drugs appear soon (at least in the next 5 years or so).
Tenofovir seems to be in your father's case the best choice in monotherapy. Like StevenNYer said, it can be considered to add-on Tenofovir to Telbivudine or either to switch to a double regimen with Tenofovir and Entecavir (more potent than Telbivudine), depening on various factors like the progression of the disease and the resistance profile of the virus.

In any case the decision has to be made by your father's doctor

[stevenNYer]

I agree with "Frade".  Telbivudine (LdT) though more potent than Lamivudine has a similar resistance profile.  It's quite high.  That's why it's surprising that it was presribed for over 2 years for your father as a monotherapy.  About 10% of LdT users also reported muscle numbness, tightness, etc.  

So switching from LdT to Entecavir and adding TDF makes a whole lot of sense.  Talk to your doctor about this.  If doctors says, "huh?"  See a second opinion.

[Pritesh1357]

Thanks Frade, Steven
I will consult the doctor on lines what you have mentioned.

[Pritesh1357]

Just consulted with doctor and he has recommended to start adefovir in addition to Telbivudine.
He said let's keep tenofovir as a last resort if cross-resistance dosen't work.

[Pritesh1357]

Can any one suggest on this course on his course of action

[stevenNYer]

In my lay, non-doctor opinion, you need to find a new doctor.  

Adefovir resistance profile is not all that great.  If you develop resistance to Adefovir, that is the stepping stone to develop resistance to Tenofovir.  You want the most antiviral power with the best resistance profile, then combine them to further cross protect.

[stef2011]

absolutely agree with steven, do change doctor absolutely and as soon as possible

adefovir was just a failure drug for hiv re-used for hbv to make some money from it...
it makes kidney damage at a dose that might work so it was put at 10mg dose which works very little and even worse has a lot of virus mutation overtime

tenofovir is 100 times more potent than adefovir, it has no resistance detected on hbv monoinfection till now so it is the best choice for hbv....we are not doctors and know all this so this can help you to get an idea of your doctor preparation

[Pritesh1357]

Thanks Steven/Stefano,
My doctor said the reason I am not starting Tenofovir is that that is the last resort if something new does not come up.
I was also reluctant to adefovir and I am thus consulting another doctor for this.
Can Telbivudine with entecavir be a good option?

[stef2011]

adefovir will lead to resistance 100% for sure and after that resistance there is almost nothing left......start tenofovir+interferon and probably you will not have resistance
are you sure you already have resistance to entecavir and lam?

i have sent you a PM with the best docotors, please follow our advise and check tx with another doctor

[Pritesh1357]

Hi,
As per the test they have said there is possible resistance to entecavir.
What is Iam? not sure of that. I am going to consult other doctor next week and let's see what he has to say.
What is the resistance profile of tenofovir taken alone?

[stef2011]

lam is lamivudine the worst antiviral with highest percentage of resistance, it is very dangerous when used monotx.

steven is more expert on resistance, i just started entecavir from 1 month so i never checked cross resistance of all antivirals.
tenofovir has no resistance detected on hbv monoinfection, only one patient on hbv-hiv coinfection had tenofovir resistance, so this would be the best choice and also interferon combo prevents resistance in combo with antiviral

anyway are you sure you have all this resistance detected correctly, it looks strange to have resistance to all antivirals

there are also 1 trial and 1 study in france and italy that you might be interested in and that can help in your case, this might be a solution for the near future:
interleukin7+tenofovir or entecavir+vaccine tx, this is to gain back some immunity and get rid of the virus.
link: http://hivandhepatitis.com/hep_b/news/2009/121109_b.html

and there is also a discovery in parma main hospital on how to restore tcell immunity which is blocked by hbv antigens, but the study will be published on jan on gastroenterology so we don't know yet full details and results about this

[Pritesh1357]

Have consulted other doctor and he said to wait for 2-3 months as current viral load is less.
I am now confused which way to go forward as there is resistance to Telbivudine and slowly viral load will also increase if we wait for 2-3 months that will affect the liver.

[stef2011]

i would check at least 2-3 doctors on this difficult situation to see if all have the same view, but in any case i wouldn't stay on a mono tx