title: Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients.
abstract: In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (-0.066 vs -0.027 PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log10IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.
authors.affiliation: INSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Boyd
authors.affiliation: Département d'Infectiologie, CHU and UMR 1347, Université de Bourgogne, Dijon, France.
authors.forename: L
authors.initials: L
authors.lastname: Piroth
authors.affiliation: Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.|Université Paris-Diderot, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Maylin
authors.affiliation: Service d'Hépatologie, Hôpital Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Maynard-Muet
authors.affiliation: Service d'Hépatologie, Hôpital Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Lebossé
authors.affiliation: Service d'Hépatologie, Hôpital Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Bouix
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lascoux-Combe
authors.affiliation: Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Mahjoub
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, UPMC Univ Paris 06, UMR_S 1136, Sorbonne Universités, Paris, France.
authors.forename: P-M
authors.initials: PM
authors.lastname: Girard
authors.affiliation: Laboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France.|Université Paris-Diderot, Paris, France.|INSERM U941, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Delaugerre
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, UPMC Univ Paris 06, UMR_S 1136, Sorbonne Universités, Paris, France.|Département de Santé Publique, Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Carrat
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, UPMC Univ Paris 06, UMR_S 1136, Sorbonne Universités, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Lacombe
authors.affiliation: Centre de Recherche sur le Cancer de Lyon, Equipes 15 et 16, INSERM, Unité 1052, UMR 5286, CNRS, Lyon, France.|Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Miailhes
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D007372:Interferons; D000068698:Tenofovir
keywords: 
  HIV
  ; chronic hepatitis B infection; pegylated interferon; time-dependent propensity score; treatment intensification