title: Virological characteristics of occult hepatitis B virus in a North American cohort of human immunodeficiency virus type 1-positive patients on dual active anti-HBV/HIV therapy.
abstract: BACKGROUND
  Occult hepatitis B virus infection (OBI) is defined as low-level HBV DNA presence in serum, liver and/or peripheral blood mononuclear cells (PBMC) in individuals that lack serum hepatitis B virus surface antigen (HBsAg). HIV+ patients with OBI may be at risk for HBV reactivation, and often receive dual active anti-HBV/HIV therapy, such as lamivudine (LMV).
  
  
  OBJECTIVE
  To determine the presence of OBI in a North American cohort of HIV-1-positive patients.
  
  
  METHODS
  45 HIV-1-positive, serum HBsAg-negative patients, reactive for antibodies to HBV core antigen (anti-HBc), were tested for HBV DNA in plasma and for HBV DNA and covalently closed circular DNA (cccDNA) in PBMC. Ten patients were re-tested after ∼5-10 years, including genotyping and clonal sequence analysis of the HBV polymerase (P) gene and overlapping HBV surface (S) gene from 8 PBMC samples.
  
  
  RESULTS
  Overall, 42% (19/45) tested HBV DNA positive, especially in PBMC (18/45), including 3/18 that were reactive for HBV cccDNA, compared to 17% (8/45) that were HBV DNA reactive in plasma. In 8 patients on LMV, sequence analysis in PBMC showed that all were HBV genotype C or D. Several carried HBV P region variants at residues associated with anti-HBV drug resistance and overlapping S gene region within the major HBsAg "a determinant".
  
  
  CONCLUSIONS
  OBI is common in HIV-positive, anti-HBc reactive patients on anti-HBV/HIV therapy, particularly in PBMC. HBV sequence analysis revealed that all had HBV genotype C or D and often had P/overlapping S gene variants possibly associated with dual-active anti-HIV/HBV therapy.
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: cscoffin@ucalgary.ca.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Coffin
authors.affiliation: Molecular Virology and Hepatology Research Group, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Mulrooney-Cousins
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Carla
authors.initials: C
authors.lastname: Osiowy
authors.affiliation: Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Veterinary Medicine, University of Calgary, AB, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: van der Meer
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nishikawa
authors.affiliation: Molecular Virology and Hepatology Research Group, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Tomasz I
authors.initials: TI
authors.lastname: Michalak
authors.affiliation: Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Guido
authors.initials: G
authors.lastname: van Marle
authors.affiliation: Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D058070:Asymptomatic Diseases; D001483:Base Sequence; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015684:Gene Products, pol / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006509:Hepatitis B / Q000097:blood* / Q000188:drug therapy* / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D009656:North America; D017422:Sequence Analysis, DNA; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D015684:Gene Products, pol; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; C066027:P protein, Hepatitis B virus; D019259:Lamivudine
keywords: Canada; Genotype; HIV; Lamivudine/3TC; Lymphoid cells; Occult HBV infection