title: Kinetics of hepatitis B surface and envelope antigen and prediction of treatment response to tenofovir in antiretroviral-experienced HIV-hepatitis B virus-infected patients.
abstract: OBJECTIVE
  Hepatitis B surface (HBsAg) and envelope (HBeAg) antigen loss are the primary goals of treating chronic hepatitis B virus (HBV). Although their quantification is useful for other antivirals, such has not been the case with tenofovir disoproxil fumarate (TDF), particularly in HIV infection.
  
  
  METHODS
  Prospective, multicenter, cohort study in 143 antiretroviral-experienced HIV-HBV-co-infected patients initiating TDF.
  
  
  METHODS
  HBsAg (IU/ml) and HBeAg levels (S/CO) were measured every 6 months. HBsAg and HBeAg decline (Δ) were assessed by mixed-effect linear models. Quantification criteria were used to assess predictability of antigen loss with time-dependent receiver operating characteristic curves.
  
  
  RESULTS
  After a median follow-up of 30.3 months, cumulative incidence rate of HBsAg loss was 4.0% (n = 4) in the entire study population and HBeAg loss was 21.0% (n = 17) in the 96 HBeAg-positive patients. ΔHBsAg was steady during follow-up (HBeAg-positive: -0.027; HBeAg-negative: -0.017 log(10) IU/ml per month), whereas ΔHBeAg ratio was strongly biphasic (-27.1 S/CO per month before and -6.5 S/CO per month after 18 months). Baseline HBeAg and ΔHBeAg were significantly different in patients harboring precore mutations (P < 0.01), whereas both ΔHBsAg and ΔHBeAg were significantly slower among HBeAg-positive patients with CD4(+) T-cell count less than 350 cells/μl (P < 0.05). HBeAg-ratio of 10 S/CO or less at 12 months of therapy was the optimal marker of HBeAg loss, with high sensitivity (0.82) and specificity (0.84) at 36 months. In patients with HBsAg loss, three of four (75.0%) patients had a baseline level of HBsAg of 400 IU/ml or less.
  
  
  CONCLUSIONS
  During TDF treatment, HIV-induced immunosuppression and HBV genetic variability are associated with differences in HBsAg and HBeAg decline among antiretroviral-experienced, co-infected patients. Considering the decline of HBsAg level is slow, further evaluation is needed to determine its role as a marker of therapeutic efficacy.
authors.affiliation: Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maylin
authors.forename: Anders
authors.initials: A
authors.lastname: Boyd
authors.forename: Fabien
authors.initials: F
authors.lastname: Lavocat
authors.forename: Joel
authors.initials: J
authors.lastname: Gozlan
authors.forename: Caroline
authors.initials: C
authors.lastname: Lascoux-Combe
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lassel
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine