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

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 0.57-1.93 year-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.