title: Rates and determinants of hepatitis B 'e' antigen and hepatitis B surface antigen seroclearance during long-term follow-up of patients coinfected with HIV and hepatitis B virus.
abstract: OBJECTIVE
  This study determines rates and risk factors associated with hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg) seroclearance, two important prognostic indicators during infection with hepatitis B virus (HBV), in a large contemporary cohort of patients coinfected with HIV-HBV.
  
  
  METHODS
  Prospective cohort study of predominately antiretroviral therapy (ART) experienced, coinfected patients.
  
  
  METHODS
  Participants enrolled in the French HIV-HBV Cohort had complete HBV serological battery conducted at inclusion and every yearly visit. Piecewise-exponential survival models were used to determine risk factors associated with seroclearance.
  
  
  RESULTS
  A total of 290 patients, of whom 151 (52.1%) were HBeAg positive, had been followed for a median 7.4 years (interquartile range [IQR] = 3.1-8.0). Tenofovir (TDF) containing ART became increasingly more frequent, as rates of undetectable HBV-DNA increased accordingly (at baseline = 39.3%, end of follow-up = 91.0%). In HBeAg-positive patients, 60 of 151 had HBeAg seroclearance (cumulative 46.4% at end of follow-up) after a median 3.0 years (IQR = 2.0-4.9). Overall, 17 of 290 patients had HBsAg seroclearance (cumulative 7.4% at end of follow-up) after a median 4.6 years (IQR = 2.1-7.2). Lower levels of time-averaged cumulative HBV-DNA were significantly associated with both HBeAg and HBsAg seroclearance (P < 0.001 and P = 0.01, respectively). In post hoc analysis among patients initiating TDF, incidence rates of HBeAg seroclearance peaked at year 4 of TDF treatment (13.1/100 person-years), whereas a steep drop in HBsAg seroclearance incidence rates occurred after year 3 (at year 3 = 1.2/100 person-years versus thereafter = 0.6/100 person-years).
  
  
  CONCLUSIONS
  HBsAg seroclearance and, to a lesser extent, HBeAg seroclearance remain difficult endpoints for patients coinfected with HIV-HBV to achieve. HBV-DNA suppression, associated with effective treatment, is strongly linked to seroclearance, but this mostly occurs within the first years of ART-containing highly potent anti-HBV activity.
authors.affiliation: aINSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique bLaboratoire de Virologie, Hôpital Saint-Antoine, AP-HP cUPMC UMRS CR7, INSERM U1135 CIMI, Paris dCentre de Recherche sur le Cancer de Lyon, Equipes 15 et 16, INSERM, Unité 1052, CNRS, UMR 5286 eService des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon fService des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, APHP gDepartment of Infectious and Tropical Diseases, Saint-Antoine Hospital, AP-HP, Paris hHepatology Unit, Hospices Civils de Lyon iUniversité de Lyon, Lyon jSorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Anders
authors.initials: A
authors.lastname: Boyd
authors.forename: Joël
authors.initials: J
authors.lastname: Gozlan
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.forename: Caroline
authors.initials: C
authors.lastname: Lascoux-Combe
authors.forename: Manuela Sébire-Le
authors.initials: MS
authors.lastname: Cam
authors.forename: Hayette
authors.initials: H
authors.lastname: Rougier
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D060085:Coinfection / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005602:France; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens