Characterization of Drug-Resistance Mutations in HBV D-genotype Chronically Infected Patients, naïve to Antiviral Drugs

Antiviral Res. 2011 Nov;92(2):382-5. doi: 10.1016/j.antiviral.2011.08.013. Epub 2011 Sep 5.

Abstract

Presence of drug-resistance mutations in drug-naïve hepatitis B virus (HBV) infected patients can seriously compromise response to antiviral treatment. Therefore, our study was aimed at defining the prevalence of HBV drug-resistance in a population of 140 patients, all infected with HBV-D-genotype (the most common HBV-genotype in Eastern Europe, Mediterranean countries and Middle East) and naïve to antiviral therapy. HBV reverse-transcriptase (RT) region was sequenced and analyzed for 20 mutations, confirmed by in vitro studies as associated with resistance to nucleos(t)ide HBV-RT inhibitors (rtL80I/V-rtI169T-rtV173L-rtL180M-rtA181T/V/S-rtT184A/S/G/C-rtA194T-rtS202C/G/I-rtM204V/I-rtN236T-rtM250V). Amino acid changes at other six RT positions, potentially associated with resistance, were also analyzed (rtV84M-rtV191I-rtV207L-rtV214A-rtQ215S-rtI233V). Overall, only 2/140 (1.4%) patients carried primary drug-resistance mutations [rtA181V (0.7%), and rtA194T (0.7%)], while 3/140 (2.1%) patients harbored the secondary mutations rtV173L (1.4%) and rtL180M (0.7%). Additionally, five polymorphic mutations, with a suggested role in drug resistance, were detected [rtQ215S (12.8%), rtI233V (4.3%), rtV214A (3.6%), rtV191I (0.7%), rtV207L (0.7%)]. Notably, no YMDD mutations, namely rtM204V/I, were found. Taken together, the rate of important drug resistance mutations in naïve HBV D-genotype infected patients is today very low, and suggests the potential full efficacy of new-generation antiviral drugs used in first line therapy. Whether such low rate can be extrapolated to non HBV-D subtypes, requires a detailed investigation to be performed in a different cohort of patients.

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Antiviral Agents / pharmacology*
  • DNA Mutational Analysis
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Drug Resistance, Viral*
  • Europe, Eastern
  • Genotype
  • Hepatitis B virus / classification
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Mediterranean Region
  • Middle Aged
  • Middle East
  • Molecular Sequence Data
  • Mutation, Missense*
  • Prevalence
  • RNA-Directed DNA Polymerase / genetics
  • Sequence Analysis, DNA
  • Viral Proteins / genetics

Substances

  • Antiviral Agents
  • DNA, Viral
  • Viral Proteins
  • RNA-Directed DNA Polymerase

Associated data

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