Rate of Resistance-Related Substitutions Does Not Affect HBV Treatment Response
Results of this study provide a theoretical basis to support the use nucleoside/nucleotide analogues with a high barrier to resistance, such as entecavir or tenofovir, as first-line therapy.
For patients with hepatitis B virus (HBV), the presence of resistance-associated substitutions does not affect the outcome of therapy if treatments with a high barrier to resistance are used, according to results published in the Journal of Viral Hepatology.
The study included treatment-naive participants with chronic HBV infection (n=232). The researchers used deep sequencing to sequence the nearly full-length HBV reverse transcriptase. They then analyzed the sequences to evaluate the prevalence of resistance-associated substitutions and fitness-associated substitutions at baseline of nucleoside and nucleotide analogues therapy, as well as their effect on treatment responses.
The researchers detected resistance-associated substitutions in 25.0% (n=58) of participants, most commonly at positions involved in lamivudine, telbivudine, and adefovir resistance. Among these participants, 29.3% (n=17) also had fitness-associated substitutions. An additional 53 participants had detectable fitness-associated substitutions not associated with resistance-associated substitutions.
Of the 58 participants with detectable resistance-associated substitutions at baseline, 22 were treated. Follow-up was available for 14 of these participants, all of whom achieved virologic response (undetectable HBV DNA 48-96 weeks after the start of treatment).
"Although [resistance-associated substitutions] were generally present in low proportions in the viral quasispecies, those conferring resistance to lamivudine, adefovir or telbivudine were often found in high proportions, as a result of their good fitness as compared to wild-type viruses," the researchers wrote. "This provides a theoretical basis to support the use [of] nucleoside/nucleotide analogues with a high barrier to resistance, such as entecavir or tenofovir, as first-line therapy, as recommended by international guidelines."
Chevaliez S, Rodriguez C, Poiteau L, et al. Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues [published online October 19, 2018]. J Viral Hepat. doi: 10.1111/jvh.13025