title: Hepatitis B virus variants in an HIV-HBV co-infected patient at different periods of antiretroviral treatment with and without lamivudine.
abstract: BACKGROUND
  Lamivudine inhibits replication of both human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and is commonly used as part of antiretroviral therapy. The main limitation in the use of lamivudine is resistant mutation selection. Most of these mutations affect the YMDD motif of the HBV DNA polymerase. The resistance occurs through M550V or M550I aminoacid replacements. The M550V variation may be accompanied by L526M mutation, notably in HIV-HBV co-infected patients. The aim of this study was to investigate mutations associated with lamivudine resistance in a hemodialysis patient chronically co-infected with HIV-1 and HBV, who was submitted to several antiretroviral treatments.
  
  
  METHODS
  HBV isolates derived from three blood samples collected at different times of antiretroviral therapies with and without lamivudine, were titred and submitted to nucleotide sequencing.
  
  
  RESULTS
  HBV isolate derived from a sample collected in 1999 during an antiretroviral treatment with lamivudine showed the lamivudine resistant double mutation (L526M, M550V). However, no mutation associated with lamivudine resistance was observed in the HBV genome derived from the sample collected during a period of treatment without lamivudine (2001). After reinstitution of lamivudine (2002), the predominant HBV population exhibited a rare triple mutation (V519L, L526M, M550V), which has previously been associated with an in vitro reduction of virus antigenicity (escape mutant). HBV DNA was detected at high levels (108-109 copies/ml) in the three blood samples.
  
  
  CONCLUSIONS
  Reintroduction of lamivudine as part of antiretroviral treatment in a patient who had developed lamivudine resistant HBV strains favored the predominance of an HBV isolate with reduced antigenicity. The absence of hepatitis acute exacerbation in this patient may be correlated to the absence of significant variations of the viral load, which was independent of the presence of mutations in the HBV DNA polymerase.
authors.affiliation: Department of Virology, Oswaldo Cruz Institute, Rio de Janeiro, RJ 21045-900, Brazil. easantos@ioc.fiocruz.br
authors.forename: Eneida A
authors.initials: EA
authors.lastname: Santos
authors.forename: Michel V F
authors.initials: MV
authors.lastname: Sucupira
authors.forename: Juçara
authors.initials: J
authors.lastname: Arabe
authors.forename: Selma A
authors.initials: SA
authors.lastname: Gomes
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D017809:Fatal Outcome; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009154:Mutation / Q000187:drug effects; D010802:Phylogeny; D016133:Polymerase Chain Reaction
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase