Circulating HBV RNA and hepatitis B core-related antigen as determinants of HBsAg loss in persons with HIV in Europe

HBsAg loss improves clinical outcomes in persons with HIV and HBV coinfection. We aimed to evaluate if hepatitis B core-related antigen and circulating HBV RNA levels were associated with HBsAg loss in Euro-B, a multi-cohort collaboration including data from the Swiss HIV Cohort Study, EuroSIDA, and the French HIV/HBV cohort.

We included persons with HIV, a positive HBsAg, and ≥6 months of follow-up on tenofovir-containing antiretroviral therapy. We evaluated quantitative HBsAg, HBV DNA, hepatitis B core-related antigen, and HBV RNA levels over time and assessed HBsAg loss (i.e. quantitative HBsAg <0.05 IU/ml) during tenofovir therapy.

Among 599 participants median age was 41 years (IQR 35-47), 18.4% were female and 47.3% HBeAg-positive. We observed HBsAg loss in 12.9% of participants after 2 years and in 18.2% during a median follow-up of 8.2 years (IQR 3.6-13.1). Individuals who were HBeAg-negative were more likely to have a negative hepatitis B core-related antigen and HBV RNA below the detection limit than participants who were HBeAg-positive. Quantitative HBsAg ≤1,000 IU/ml at baseline was the strongest predictor of HBsAg loss regardless of HBeAg status. Additionally, HBsAg loss was associated with lower baseline HBV RNA levels (odds ratio 0.66, 95% CI 0.49-0.88) and higher baseline HBV DNA levels in participants who were HBeAg-positive.

In this European cohort of persons with HIV/HBV, 18% experienced HBsAg loss during tenofovir-containing antiretroviral therapy. In addition to low baseline quantitative HBsAg levels, HBV RNA may predict HBsAg loss in individuals who are HBeAg-positive.

The present study builds on a multi-cohort collaboration including persons with HIV/HBV from Europe. It provides estimates on the probability of HBsAg loss during long-term tenofovir-containing antiretroviral therapy and describes the potential of the novel biomarkers HBV RNA and hepatitis B core-related antigen as its predictors. The discrepancies regarding HBV RNA and HBcrAg levels before and during therapy observed between persons who were HBeAg-negative and HBeAg-positive with HIV/HBV may influence treatment decisions and the development of new treatment strategies.

The study is registered at ClinicalTrials.gov (NCT04984772).