HR : What is Viread/LAM Combo Resistance Profile?

[Ann8]

HR - Found your comment on taking this combo for better resistance profile very interesting and refreshing. Always gain new knowledge reading your posts. Is your suggestion base on HIV Viread/ETC resistance profile? How long can this combo goes without resistance? Thanks in advance

[Ann8]

What if resistance developed to this combo? Any rescue drug? Thanks

[cajim]

My hepatologist would say before resistance develops, other new drugs will be out.

[Hepatitis Researcher]

Ann8    just like with hepsera, if a primary resistance mutation to Tenofovir would occur, the simultaneous LAM will suppress the propagation of this mutated species, preventing it to get to higher numbers. This always is based of course on the assumption that no a priory LAM mutation is in existence. Thus now after many years it is now routinely recommended to start hepsera together with LAM. While Tenofovir has a dramatically lower inherent chance to go into resistance compared with Adefovir ( almost 30 fold power) , the fundamental consideration is the same. If resistance would develop to the TDF/LAM combo, Entecavir would still work, limpingly, but secondary resistance could be expected. Somewhat higher expectations of effectiveness/ resistance preventive power can be placed in the use of the FTC/TDF combo  a drug already in use for HIV under the name Truvada.
FTC is very similar to LAM, just has an extra Fluor atom on the ring. There was an HBV  trial in Honkong a while ago where the combo FTC/ADF was vastly superior to ADF alone, showing almost synergism in Vl reduction, this has been  reported at the AASLD.

To Cajim : Your hepatologist is wrong, there is very little chance that other, new HBV drugs will come out now for a long time, that could overcome a LAM/TDF/ETV resistance. Once the routine will be to treat patients with combos from the start, resistance development will dramatically be lowered, in particular if the super-combos are used from day one. If the current practice to produce resistance by mono-therapy continues too long, there could be a substantial percentage of de novo infections with resistant variants from day one, those could be a real problem.

[cajim]

Thanks, HR.  I wish all experts could be more serious about resistance rather than relying on the vague hope that ETV etc will give you five years' time and after that new drugs will be out.

[stevenNYer]

"there could be a substantial percentage of de novo infections with resistant variants from day one, those could be a real problem."

I didn't think about that...wow, that's pretty scary.

[Ann8]

what is de novo infections.....? Pls explain. Thank you

[stevenNYer]

It means a new infection in a different form.  For example, if a current patient who starts off with wild-type HBV, treats and develop resistance to multiple antivirals.  That pt will have the multi-resistant HBV strain(s) as the primary specie.  Should he/she  infects someone NEW, that new infection will be that of the multi-resistant strain (s) that would be very difficult to treat since resistant is already there.

So in a sense all this mono-treatment leading to resistant could cause a meaner and angrier HBV.

[NashPred]

Interesting…..

Is it possible that a “de novo infection” would be able to infect someone who has already been vaccinated or is already immune due to clearance of a past infection? Or would anti-HBs not have any problem attacking this type of infection like antiviral medications would?

[stevenNYer]

"Is it possible that a “de novo infection” would be able to infect someone who has already been vaccinated or is already immune due to clearance of a past infection?"

I think I read somewhere that the answer is no.  Something to do with the anti-HBs being able to bind to a certain area of the virus and eliminating it quickly.  Anyone able to confirm and / or add to this?

[neodyme]

If resistance occur to Truvada (in the long run), would Entecavir be the rescue drug, alone or in combo and which one ?