Development of anti-hepatitis B surface (HBs) antibodies after HBs antigen loss in HIV-hepatitis B virus co-infected patients

J Clin Virol. 2017 Oct:95:55-60. doi: 10.1016/j.jcv.2017.08.008. Epub 2017 Aug 25.

Abstract

Background: Hepatitis B surface antigen (HBsAg)-seroconversion, or loss of HBsAg and acquisition of anti-hepatitis B surface (HBs) antibodies, defines functional cure of chronic hepatitis B virus (HBV) infection. After HBsAg-loss, little is known regarding the development of anti-HBs antibodies and even less so in individuals co-infected with HIV.

Objectives: To determine anti-HBs antibody kinetics after HBsAg-loss and explore determinants of HBsAg-seroconversion in HIV-HBV co-infected patients.

Study design: Patients enrolled in the French HIV-HBV cohort were included if they had >1 study visit after HBsAg-loss. Individual patient kinetics of anti-HBs antibody levels were modeled over time using mixed-effect non-linear regression, whereby maximum specific growth rate and maximal level of antibody production were estimated from a Gompertz growth equation.

Results: Fourteen (4.6%) of 308 co-infected patients followed in the cohort exhibited HBsAg-loss, all of whom were undergoing antiretroviral therapy. Nine (64.3%) of these patients achieved HBsAg-seroconversion during a median 3.0 years (IQR=1.1-5.1) after HBsAg-loss. Across individuals with HBsAg-seroconversion, the fastest rates of antibody growth ranged between 0.57-1.93year-1 (population maximum growth rate=1.02) and antibody production plateaued between 2.09-3.66 log10 mIU/mL at the end of follow-up (population maximal antibody levels=2.66). Patients with HBsAg-seroconversion had substantial decreases in HBV DNA viral loads (P=0.03) and proportion with elevated ALT levels (P=0.02) and HBeAg-positive serology (P=0.08). No such differences were observed in those without HBsAg-seroconversion.

Conclusions: Most co-infected patients with HBsAg-seroconversion produced and maintained stable antibody levels, yet kinetics of anti-HBs production were much slower compared to those observed post-vaccination or after clearance of acute HBV-infection.

Keywords: Anti-HBs antibodies; Antiretroviral therapy; HBsAg-seroconversion; Kinetics; Logistic growth model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Coinfection*
  • DNA, Viral / blood
  • Female
  • HIV Infections / complications*
  • HIV Infections / virology
  • Hepatitis B Antibodies / biosynthesis*
  • Hepatitis B Antibodies / blood*
  • Hepatitis B Antibodies / immunology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Seroconversion
  • Serologic Tests
  • Viral Load

Substances

  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens