Mutations associated with drug resistance and prevalence of vaccine escape mutations in patients with chronic hepatitis B infection

J Med Virol. 2017 Oct;89(10):1811-1816. doi: 10.1002/jmv.24853. Epub 2017 Jul 21.

Abstract

The Brazilian public health system (SUS) has provided antiviral drugs for chronic hepatitis B treatment for over 10 years, but a system for monitoring for drug-related resistance mutations is not available. Determine the presence of HBV mutations associated with resistance to nucleos(t)ide analogs among 81 patients with chronic HBV infection in Salvador-BA-Brazil. HBV-DNA was PCR amplified with primers deduced from the rt domain at the HBV P gene, the sequence extended 1032 bp (from amino acid 1 to 344-rt domain). Those sequences were submitted to the HBV drug resistance database to retrieve each mutation according to the genotype. HBV genotype A1 (85.2%) was the most prevalent, followed by genotype A2 (4.9%), F (6.2%), and C1, D2, and D4 (1.2% each). Six patients (7%) exhibited resistance mutations to LAM, ETV, and TDF: two with patterns L180M + M204V and four with other different patterns: L80I + L180M + M204I; L80V + L180M + M204V; M204I; A194T. All of these mutations were present in patients with genotype A (four A1 and two A2). In addition, four mutations in gene S (three cases with the sI195M mutation and one with the W196L mutation), were detected, corresponding to a rate of 6% of vaccine escape mutations. Althougth the small sample size, an association was found between the occurrence of HBV resistance mutations and HBeAg positivity, co-infection with HIV and a history of treatment for HBV and/or HIV.

Keywords: HBV; hepatitis B virus; nucleos(t)ides analogs; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Brazil / epidemiology
  • Coinfection / epidemiology
  • Coinfection / virology
  • DNA, Viral / genetics
  • Drug Resistance, Viral / genetics*
  • Genotype
  • Hepatitis B Vaccines
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / epidemiology
  • Hepatitis B, Chronic / virology*
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Mutation
  • Organophosphonates / therapeutic use

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Vaccines
  • Organophosphonates
  • Lamivudine