Circulating HBV RNA and hepatitis B core-related antigen as determinants of HBsAg loss in persons with HIV in Europe
Among persons with HIV and hepatitis B virus (HBV) coinfection, loss of hepatitis B surface antigen (HBsAg) is associated with improved clinical outcomes but occurs infrequently during antiviral therapy. In a study published in JHEP Reports, Begré et al. investigated whether circulating HBV RNA and hepatitis B core-related antigen (HBcrAg) levels are associated with HBsAg loss during tenofovir-containing antiretroviral therapy (ART) in Euro-B, a multi-cohort collaboration including data from the Swiss HIV Cohort Study, EuroSIDA, and the French HIV/HBV cohort.
The study included 599 participants with HIV, a positive HBsAg at the start of tenofovir therapy, and at least six months of follow-up. Quantitative HBsAg (qHBsAg), HBV DNA, HBcrAg, and HBV RNA levels were measured at tenofovir start, after two years, and at the last available follow-up visit over a median of 8.2 years (IQR 3.6–13.1). Multivariable logistic regression, stratified by hepatitis B e antigen (HBeAg) status, was used to identify predictors of HBsAg loss.
HBsAg loss occurred in 12.9% of participants after two years and in 18.2% (n=109) during the full follow-up period. Low baseline qHBsAg (≤1’000 IU/ml) was the strongest predictor of HBsAg loss in participants with a negative HBeAg (odds ratio 6.82, 95% CI 3.39–13.70) and those with a positive HBeAg (odds ratio 4.98, 95% CI 1.59–15.58). In participants with a positive HBeAg, lower baseline HBV RNA levels were additionally associated with HBsAg loss (odds ratio 0.66, 95% CI 0.49–0.88 per 1 log₁₀ cp/ml increase), whereas HBcrAg levels were not. Notably, HBcrAg and HBV RNA levels declined over time regardless of HBsAg loss, with most individuals with a negative HBeAg reaching undetectable levels.
In summary, approximately one in five persons with HIV/HBV experienced HBsAg loss over eight years of tenofovir-containing ART, with low baseline qHBsAg being the dominant predictor across HBeAg strata. HBV RNA may serve as an additional prognostic marker in individuals with a positive HBeAg and should be considered when assessing the likelihood of HBsAg loss. These findings underscore the importance of distinguishing between participants with HIV/HBV with a negative and a positive HBeAg and may inform the development of stratified treatment and monitoring strategies.