title: Long-term hepatitis B virus dynamics in HIV-hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate.
abstract: BACKGROUND
  The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV-HBV-co-infected patients.
  
  
  METHODS
  We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models.
  
  
  RESULTS
  The HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients. Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P < 0.05). HBV-DNA decay was biphasic, with an rapid fall followed by a gradual decline. Baseline factors associated with a steeper first slope in the HBV-DNA decrease were high HBV load, positive hepatitis B e antigen (HBeAg) and YMDD mutations. Baseline factors increasing the time to reach an HBV-DNA level less than 200 copies/ml were high HBV load (150 days when HBV-DNA < 10 log, 316 days when HBV-DNA > 10 log) and positive HBeAg. Previous exposure to lamivudine or TDF-lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations.
  
  
  CONCLUSIONS
  The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, the clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV-HBV-co-infected patients, regardless of HBV strains and their degree of replication.
authors.affiliation: Inserm U707, Université Pierre et Marie Curie, 27 rue de Chaligny, 75571 Paris cedex 12, France. karine.lacombe@sat.aphp.fr
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
authors.forename: Joël
authors.initials: J
authors.lastname: Gozlan
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Boelle
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Alain-Jacques
authors.initials: AJ
authors.lastname: Valleron
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D000068698:Tenofovir; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine