Kinetics and predictors of Hepatitis B surface antigen (HBsAg) loss after commencing HBV-active antiretroviral therapy (ART) in the setting of HIV-and chronic HBV co-infection.

Background: An effective therapeutic strategy for HBV cure remains an urgent unmet need. We aimed to define the incidence, kinetics and predictors of hepatitis B surface antigen (HBsAg) loss in people living with HIV and HBV (PLWH-HBV) following HBV-active antiretroviral therapy (ART) in PLWH-HBV in Asia.

Method: 97 PLWH-HBV commencing HBV-active ART were recruited prospectively in Thailand (n=94) and Malaysia (n=3) then followed for 24 months. Time to HBV serology change was calculated. Univariate associations between baseline characteristics and HBsAg loss were examined using the Mann-Whitney or Chi-square tests. Multivariable analysis was undertaken using Cox regression.

Results: 21 individuals (22%) lost HBsAg during follow-up (11.7 per 100 PY), 14 of whom gained anti-HBs. 22/61 (36.1%) individuals who were hepatitis B "e" antigen (HBeAg) positive at baseline lost HBeAg over the study, 15 of whom gained anti-HBe. Most individuals lost HBsAg and HBeAg by the month 12 study visit (81% and 63.6%, respectively), with median times of 5.8 and 12.0 months to HBsAg and HBeAg loss, respectively. Univariate analysis showed baseline characteristics associated with HBsAg loss were higher alanine aminotransferase (ALT, p=0.005), tenofovir alafenamide (TAF)-containing ART regimen (p=0.025), younger age (p=0.040), lower liver stiffness (p=0.010) and quantitative HBsAg< log102.0 IU/ml (p=0.001). All 5 factors remained significant in a Cox regression analysis that adjusted for baseline CD4 count.

Conclusions: High HBsAg loss rates occur in people living with HIV and HBV early after commencing ART. Our study suggests that TAF-containing ART regimens may be preferable as first line therapy in HIV-HBV co-infection.