Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues

Abstract

Summary Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long‐term administration as monotherapies. The prevalence of resistance‐associated substitutions (RASs) and fitness‐associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment‐naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full‐length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment‐naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next‐generation sequencing at baseline who were treatment‐eligible and treated with currently recommended drugs achieved a virological response. The presence of pre‐existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico

“…22,43 The heterogeneous distribution of HBV drug-resistance mutations could be explained by factors such as the use of different detection methods (line probe assay, Sanger DNA sequencing, or next generation sequencing), the number of samples analyzed, accessibility of antiviral in each region, the period during which the studies were conducted, and even the distribution of HBV genotypes. [35][36][37][38][39][40][41][42][43] Here, we showed that HBV resistance mutations were common in genotypes H and A2. As mentioned before, the prevalence of genotype H was expected as it is predominant in Mexico.…”

“…The highest frequencies have been detected in Italy (72.1%), 40 and a rate of 42.8% has been reported in ethnic regions of China. 41 Chevaliez et al 42 found a resistance frequency of 25.0% in France. In North America and Brazil, frequencies of 21.0% and 1.6% were reported, respectively.…”

Evolution and phenotypic characterization of whole HBV genome in compliant patients experiencing unexplained entecavir treatment failure

“…First, it does not take into account polymorphisms selected outside of the Pol/RT domain and associated with different clinical phenotypes of chronic hepatitis B (Huang et al, 2013;Peng et al, 2017;Podlaha et al, 2019). Second, unlike deep sequencing, it is unsuitable for the sensitive detection of minor variants before (Chevaliez et al, 2019) or after treatment failure (Lee et al, 2018;Lowe et al, 2016). This conventional approach fails to detect any Pol/RT resistance mutations in some patients experiencing treatment failure on entecavir.…”

Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors

“…They inhibit transcription and/or replication of different RNA and DNA viruses by targeting components of the viral replication machinery. However, it is established that numerous viruses eventually mutate and develop resistance to these molecules 11-13 . To circumvent this limitation, newly designed BSA overtake the drug resistance problem by targeting host cellular pathways hijacked by the virus to replicate instead of viral factors themselves.…”