Hepatitis B virus resistance substitutions: long-term analysis by next-generation sequencing.

HBV phylogenetics and resistance-associated mutations (RAMs) were surveyed by next-generation sequencing of 21 longitudinal samples from seven patients entering antiviral therapy. The virus populations were dominated by a few abundant lineages that coexisted with substantial numbers of low-frequency variants. A few low-frequency RAMs were observed before treatment, but new ones emerged, and their frequencies increased during therapy. Together, these results support the idea that chronic HBV infection is dominated by a few virus lineages and that an accompanying plethora of diverse, low-frequency variants may function as a reservoir that potentially contribute to viral genetic plasticity, potentially affecting patient outcome.