There are two stages of viral mutations that lead to drug resistance. The first stage produces viral quasispecies that are not particularly fit for robust replication. An example of this is the well-known YMDD mutation. A second mutation, termed a compensatory mutation, occurs when this first mutation gives rise to a mutant strain that replicates more effectively.
The recognized risk factors for the development of drug resistant HBV strains include: high pre-treatment viral load, prior exposure to the medication, and longer duration of treatment.
So, now you know what it is and why it happens, but how do you detect it? Monitor viral loads every 3 to 6 months and look out for the following: biochemical breakthrough (ALT > 2x ULN), flare (ALT > 10x ULN), virologic breakthrough (> 1 log rise) and rebound (VL > 20,000 IU/mL). Be skeptical about patient non-compliance with the drug regimen when this happens.