resistance to entecavir after achieving a late virological response

[stef2011]

Genotypic resistance to entecavir in lamivudine naive patients after achieving a virological response for chronic hepatitis B

2Dept of Virology, Erasmus MC University Medical Center Rotterdam,
Rotterdam, The Netherlands,
3Victorian Infectious Diseases Reference Laboratory, North Melbourne, Australia
The risk of entecavir (ETV) resistance is low in lamivudine (LAM) naïve patients, especially after
achieving an undetectable HBV DNA by sensitive PCR. EASL guidelines thus suggest decreasing
frequency of expensive HBV DNA monitoring after confirming efficacy. Patients were 3-6 monthly
monitored for HBV DNA and ALT. Resistance testing was performed when virological breakthrough
(VB) occurred (>1 log increase in HBV DNA from the  nadir). Resistance analysis was performed
both by LiPA and conventional polymerase sequencing. This study describes 4 out of 108 LAM-naïve
HBV patients treated with ETV who developed resistance within our centre. All 4 had wildtype at
base and an HBV DNA >6.5 log IU/mL. Three were HBeAg+ and genotype A, of whom 1 was
pretreated with adefovir (no resistance) and treated with 1 mg. The other was HBeAg-, with
genotype D. Base analysis showed that HBV DNA was significantly higher than 104 patients who did
not develop ETV resistance (7.6 vs. 6.0; p=0.001); other parameters were comparable. HBV DNA
kinetics show that all 4 patients achieve a fast dec of >3 log IU/mL within the first 2-4 months.
Thereafter viral dec flattens and a plateau phase with only moderate dec in HBV DNA is entered
resulting in an HBV DNA after 12 months of ETV therapy ranging from 4.1-5.4 log IU/mL. HBV DNA
slowly further declined within the second year resulting in a load below 3 log IU/mL for all patients.
Three patients achieved a virological response (5xULN) in one patient who also
experienced an increase in serum HBsAg of >1 log IU/mL. All 4 patients were switched to the
combination of TDF and ETV with satisfactory results.
Conclusions: High base HBV DNA and late achievement of undetectable HBV DNA appeared related
to developing ETV resistance. Infrequent monitoring of HBV DNA after achieving virological
response should be re-evaluated in those achieving an undetectable HBV DNA after the first 2 years
of ETV therapy.

[veteranB]

That is why we need to stop the practice  of use of nucs for a long time. They are good in a combo with immune  modulators for a year to 24 months and safety record seems to acceptable.

They the drug companies knew this btw all of it that this would happen from observing the hiv patients.

[akini]

A billion thanks to you for the help you've rendered to humanity through your thread.
Reading through I have known more tonight more than what I have known since I was diagnosed put together.
I'm going to bed tonight a better/hopeful man.

I'm expecting my results next week.

Thank you

[Aydin1358]

Interesting article! Thanks so much Stef.

One question I was wondering about. So what will be the danger of developing resistance to ETV, if after taking TDF you will resolve the resistance problem? Is it really the resistance problem solved by making HBV DNA undetectable after taking TDF?