HBV Drug resistance Flashcards
Lamivudine has low barrier to resistance
What common mutations provides resistance to lamivudine?
L180M
M204I
M204V
mutations occur in HBV DNA polymerase
HIV Resistance mutation NRTI (similar name)
M184V/I
Common resistance mutations:
L180M
M204V
M204I
Which drugs will remain sensitive, and which will be resistant?
Adefovir
Entecavir
Lamivudine
Tenofovir
Susceptible
- Tenofovir
Intermediate
- Entecavir
- Adefovir
Resistant
- Lamivudine
HIV M184V mutation - resistance
Lamivudine
Emtricitabine
Drug resistance profiles. What drug would you switch to?
LAM resistance
TBV resistance
ETV resistance
LAM resistance Switch to TDF or TAF
TBV resistance Switch to TDF or TAF
ETV resistance Switch to TDF or TAF
Drug resistance profiles. What drug would you switch to?
ADV resistance
- If LAM-naïve: switch to ETV or TDF or TAF
- If LAM-resistance: switch to TDF or TAF
- If HBV DNA plateaus: add ETV*** or switch to ETV
Drug resistance profiles. What drug would you switch to?
TDF/ TAF resistance
- If LAM-naïve: switch to ETV
- If LAM-R: add ETV*
Drug resistance profiles. What drug would you switch to?
Multidrug resistance
Switch to ETV plus TDF or TAF combination
HBV drug resistance
Where do mutations in HBV occur?
Nucleoside- and nucleotide-analogues selectively target HBV DNA polymerase, resulting in premature chain termination of viral replication.
Drug-resistant strains of HBV have signature mutations in the reverse transcriptase domains of the viral polymerase gene
Resistance mutations alter the interaction between HBV polymerase and drug, which interfere the inhibitory effect of drug on viral polymerase.
After emergence of primary resistance mutations, compensatory mutations that restore replication capacity may arise , as well as secondary resistance mutations that increase drug resistance when they accumulate on the same viral genome
HBV drug resistance
After stopping treatment, how long does it take for mutations to be “forgotten”?
They usually persist.
Mutations in DNA virus will last indefinitely
So if fail treatment on a drug, unlikely you can ever use that drug again
How is drug resistance defined?
Clinical or virologic response
Clinical - no response to treatment, or 1log10 rise in viral load may typically constitute clinical failure
Virological - plaque reduction assay shows reduced efficacy. Resistance can be high/intermediate/ low
Which HBV resistance mutations provide resistance to entecavir?
Entecavir is an antiviral drug with a high genetic barrier of resistance
Drug resistance requires at least three mutations including:
L180M
M204V
plus another mutation at T184, S202, or M250.
If only 1 mutation is present, it may be fully lamivudine resistant, but intermediate resistant to entecavir
What HBV resistant mutations provide resistance to Tenofovir?
High barrier to resistance
Needs at least 4 mutations to acquire resistance
