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

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. Design: 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). Conclusion: 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.