title: HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons.
abstract: BACKGROUND
  Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood.
  
  
  METHODS
  HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined.
  
  
  RESULTS
  143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine.
  
  
  CONCLUSIONS
  In HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF-containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation.
authors.affiliation: Cantonal Hepatobiliary Unit, Ente Ospedaliera Cantonale, Ospedale San Giovanni Bellinzona,Switzerland and Gastroenterology and Hepatology Service, University Hospital of Geneva, Geneva, Switzerland. florian.bihl@eoc.ch.
authors.forename: Florian
authors.initials: F
authors.lastname: Bihl
authors.affiliation: Institute of Microbiology, Ente Ospedaliera Cantonale, Bellinzona, Switzerland. gladys.martinetti@eoc.ch.
authors.forename: Gladys
authors.initials: G
authors.lastname: Martinetti
authors.affiliation: Department of Infectious Diseases, University Hospital of Bern, and Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. gwandeler@ispm.unibe.ch.
authors.forename: Gilles
authors.initials: G
authors.lastname: Wandeler
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland. Rainer.Weber@usz.ch.
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland. infled@usz.uzh.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergeber
authors.affiliation: Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland. Alexandra.Calmy@hcuge.ch.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.affiliation: Division of Infectious Diseases, University Hospital of Basel, Basel, Switzerland. Manuel.Battegay@usb.ch.
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.affiliation: Division of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland. Matthias.Cavassini@chuv.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.affiliation: Division of Infectious Diseases, Cantonal Hospital of S. Gallen, St. Gallen, Switzerland. pietro.vernazza@kssg.ch.
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.affiliation: Institute of Microbiology, Ente Ospedaliera Cantonale, Bellinzona, Switzerland. annapaola.caminada@eoc.ch.
authors.forename: Anna-Paola
authors.initials: AP
authors.lastname: Caminada
authors.affiliation: SHCS Datacenter, Lausanne, Switzerland. Martin.Rickenbach@chuv.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Rickenbach
authors.affiliation: Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland. Enos.bernasconi@eoc.ch.
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013557:Switzerland; D000068698:Tenofovir / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D019259:Lamivudine; D000068698:Tenofovir