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

Lorin Begré; Anders Boyd; Marie-Laure Plissonnier; Barbara Testoni; Charles Béguelin; Franziska Suter-Riniker; Caroline Scholtès; Jürgen K Rockstroh; Karine Lacombe; Lars Peters; Marintha Heil; Massimo Levrero; Andri Rauch; Fabien Zoulim; Gilles Wandeler; Swiss HIV Cohort Study, EuroSIDA and French HIV/HBV and Biliver cohorts; Members of the EuroSIDA Study Group; Members of the French HIV/HBV and Biliver cohorts

doi:10.1016/j.jhepr.2025.101671

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

JHEP Rep. 2025 Nov 7;8(2):101671. doi: 10.1016/j.jhepr.2025.101671. eCollection 2026 Feb.

Authors

Lorin Begré^{1

2}, Anders Boyd^{3

4

5}, Marie-Laure Plissonnier^{6

7}, Barbara Testoni^{6

7}, Charles Béguelin¹, Franziska Suter-Riniker⁸, Caroline Scholtès^{6

7

9}, Jürgen K Rockstroh¹⁰, Karine Lacombe^{11

12}, Lars Peters¹³, Marintha Heil¹⁴, Massimo Levrero^{6

7

15}, Andri Rauch¹, Fabien Zoulim^{6

7

15}, Gilles Wandeler^{1

16}; Swiss HIV Cohort Study, EuroSIDA and French HIV/HBV and Biliver cohorts; Members of the EuroSIDA Study Group; Members of the French HIV/HBV and Biliver cohorts

Collaborators

Swiss HIV Cohort Study, EuroSIDA and French HIV/HBV and Biliver cohorts:
Irene A Abela, Karoline Aebi-Popp, Alexia Anagnostopoulos, Manuel Battegay, Enos Bernasconi, Dominique L Braun, Heiner C Bucher, Alexandra Calmy, Matthias Cavassini, Angela Ciuffi, Günter Dollenmaier, Matthias Egger, Luisa Elzi, Jan S Fehr, Jacques Fellay, Hansjakob Furrer, Christoph A Fux, Huldrych F Günthard, Anna Hachfeld, David Hans-Ulrich Haerry, Barbara Hasse, Hans H Hirsch, Matthias Hoffmann, Irene Hösli, Michael Huber, David Jackson-Perry, Christian R Kahlert, Olivia Keiser, Thomas Klimkait, Roger D Kouyos, Helen Kovari, Katharina Kusejko, Niklaus D Labhardt, Karoline Leuzinger, Begoña Martinez de Tejada, Catja Marzolini, Karin J Metzner, Nicolas Müller, Johannes Nemeth, Dunja Nicca, Julia Notter, Paolo Paioni, Giuseppe Pantaleo, Matthieu Perreau, Andri Rauch, Luisa Paola Salazar-Vizcaya, Patrick Schmid, Olivier Segeral, Speck R F, Marcel Stöckle, Philip E Tarr, Alexandra Trkola, Gilles Wandeler, Maja Weisser, Sabine Yerly
Members of the EuroSIDA Study Group:
A Harxhi, M Losso, M Kundro, M Knappik, P Cichon, Klinik Penzing, M Sarcletti, I Karpov, V M Mitsura, D Paduto, N Clumeck, S De Wit, M Delforge, M Frankenhuijsen, M De Scheerder, J Topalovic, J Begovac, D Jilich, L Machala, D Sedlacek, T Benfield, J Gerstoft, A M Lebech, O Kirk, I S Johansen, L Ostergaard, L Wiese, L N Nielsen, K Zilmer, I Aho, J-P Viard, K Lacombe, C Pradier, E Fontas, C Duvivier, J Rockstroh, O Degen, C Hoffmann, C Stefan, J Bogner, C Lehmann, A Abutidze, H Sambatakou, G Adamis, N Paissios, J Szlávik, M Gottfredsson, E Devitt, L Tau, O A Bondarenko, L M Wattad, H Elinav, D Elbirt, G Marchetti, G Guaraldi, C Mussini, A Castagna, A Ridolfo, F Schiavo, V Uzdaviniene, R Matulionyte, T Staub, R Batutu, M Vd Valk, J Trajanovska, D H Reikvam, B Knysz, B Szetela, M Inglot, E Bakowska, M Parczewski, B Aksak-Was, M Beniowski, E Mularska, E Jablonowska, J Kamerys, K Wojcik, I Mozer-Lisewska, B Rozplochowski, A Zagalo, K Mansinho, F Maltez, R Radoi, C Oprea, D Gusev, T Trofimova, E Kuzovatova, E Borodulina, E Vdoushkina, J Ranin, J Tomazic, E Martínez, J M Miró, M Laguno, J L Blanco, M Martinez-Rebollar, J Ambrosioni, B Torres, L de la Mora, A Gonzalez-Cordon, I Chivite, A Foncillas, E de Lazzaari, L Berrocal, P Callau, A Inciarte, J Alcami, J Mallolas, R Paredes, J Puig, J R Santos, C Miranda, P Domingo, G M Mar, M G Gracia, E S De A Arroniz, A Ponz, C Carlander, A Sönnerborg, J Brännström, K Falconer, F Månsson, K Kusejko, D Braun, M Cavassini, A Calmy, H Furrer, M Battegay, P Schmid, E Bernasconi, A Kuznetsova, L Hetman, A Kryshchuk, M Boffito, S Edwards, F Burns, C Orkin, A Winston, A Clarke, C Mackintosh, C Boesecke, C Carlander, C Pradier, C Oprea, E Martinez, G Wandeler, I Aho, I Karpov, J Begovac, J D Kowalska, J Lundgren, L D Rasmussen, L Tau, O Nesterova, R Matulionyte, S Nozza, J D Kowalska, L Peters, L Peters, J F Larsen, M Gardizi, N Jaschinski, A Timiryasova, B Neesgaard, F Roper, D Raben, A H Fischer, A Cozzi-Lepri, W Bannister, T W Elsing, L R Kumar, S Shahi, B Pepa
Members of the French HIV/HBV and Biliver cohorts:
Anders Boyd, Patrick Miailhes, Caroline Lascoux-Combe, Julie Chas, Pierre-Marie Girard, Joël Gozlan, Fabien Zoulim, Constance Delaugerre, Hayette Rougier, Karine Lacombe

Affiliations

¹ Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
³ Stichting HIV Monitoring, Amsterdam, The Netherlands.
⁴ Department of Infectious Diseases, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands.
⁶ UMR PaThLiv U1350, Inserm, Université Claude Bernard Lyon 1, Lyon, France.
⁷ Lyon Hepatology Institute, IHU EVEREST, Lyon, France.
⁸ Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
⁹ Department of Virology, Hospices Civils de Lyon, Lyon, France.
¹⁰ HIV-Clinic, Department of Medicine I, University Hospital Bonn, Bonn, Germany.
¹¹ Sorbonne Université, Inserm, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France.
¹² AP-HP, GH Sorbonne.Université, Hôpital Saint-Antoine, Service de maladies infectieuses et tropicales, Paris, France.
¹³ CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, Copenhagen, Denmark.
¹⁴ Roche Molecular Diagnostics, Pleasanton, CA, USA.
¹⁵ Department of Hepatology, Hospices Civils de Lyon, Lyon, France.
¹⁶ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Abstract

Background & aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Impact and implications: 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.

Clinical trials registration: The study is registered at ClinicalTrials.gov (NCT04984772).

Keywords: Cohort studies; Coinfection; HBV RNA; HIV; Hepatitis B core-related antigen; Hepatitis B virus; Tenofovir.

Associated data

ClinicalTrials.gov/NCT04984772