Circulating HBV RNA and hepatitis B core-related antigen trajectories in persons with HIV/HBV coinfection and HBsAg loss on tenofovir therapy

Lorin Begré; Anders Boyd; Marie-Laure Plissonnier; Barbara Testoni; Luisa Salazar-Vizcaya; Franziska Suter-Riniker; Caroline Scholtès; Charles Béguelin; Jürgen K Rockstroh; Huldrych F Günthard; Alexandra Calmy; Matthias Cavassini; Hans H Hirsch; Patrick Schmid; Enos Bernasconi; Massimo Levrero; Gilles Wandeler; Fabien Zoulim; Andri Rauch; Swiss HIV Cohort Study

doi:10.1093/infdis/jiae189

Circulating HBV RNA and hepatitis B core-related antigen trajectories in persons with HIV/HBV coinfection and HBsAg loss on tenofovir therapy

J Infect Dis. 2024 Apr 16:jiae189. doi: 10.1093/infdis/jiae189. Online ahead of print.

Authors

Lorin Begré^{1

2}, Anders Boyd^{3

4

5

6}, Marie-Laure Plissonnier⁷, Barbara Testoni⁷, Luisa Salazar-Vizcaya¹, Franziska Suter-Riniker⁸, Caroline Scholtès^{7

9}, Charles Béguelin¹, Jürgen K Rockstroh¹⁰, Huldrych F Günthard^{11

12}, Alexandra Calmy¹³, Matthias Cavassini¹⁴, Hans H Hirsch¹⁵, Patrick Schmid¹⁶, Enos Bernasconi¹⁷, Massimo Levrero⁷, Gilles Wandeler¹, Fabien Zoulim⁷, Andri Rauch¹; Swiss HIV Cohort Study

Collaborators

Swiss HIV Cohort Study:
I Abela, K Aebi-Popp, A Anagnostopoulos, M Battegay, E Bernasconi, D L Braun, H C Bucher, A Calmy, M Cavassini, A Ciuffi, G Dollenmaier, M Egger, L Elzi, J Fehr, J Fellay, H Furrer, C A Fux, H F Günthard, A Hachfeld, D Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, M Huber, D Jackson-Perry, C R Kahlert, O Keiser, T Klimkait, R D Kouyos, H Kovari, K Kusejko, N Labhardt, K Leuzinger, B Martinez de Tejada, C Marzolini, K J Metzner, N Müller, J Nemeth, D Nicca, J Notter, P Paioni, G Pantaleo, M Perreau, A Rauch, L Salazar-Vizcaya, P Schmid, R Speck, M Stöckle, P Tarr, A Trkola, G Wandeler, M Weisser, S Yerly

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 Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, The Netherlands.
⁴ stichting hiv monitoring Amsterdam, Amsterdam, The Netherlands.
⁵ Amsterdam UMC location University of Amsterdam, Infectious Diseases, Meibergdreef 9, Amsterdam, The Netherlands.
⁶ Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, The Netherlands.
⁷ Inserm Unit 1052, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon Hepatology Institute, Lyon, France.
⁸ Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
⁹ Laboratoire de Virologie, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
¹⁰ HIV-Clinic, Department of Medicine I, University Hospital Bonn, Bonn, Germany.
¹¹ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
¹² Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
¹³ Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
¹⁴ Division of Infectious Diseases, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
¹⁵ Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁶ Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
¹⁷ Division of Infectious Diseases, Ente Ospedaliero Cantonale Lugano, University of Geneva and University of Southern Switzerland, Lugano, Switzerland.

PMID: 38626170
DOI: 10.1093/infdis/jiae189

Abstract

Background: We evaluated long-term trajectories of circulating hepatitis B virus (HBV)-RNA and hepatitis B core-related antigen (HBcrAg) in persons with and without hepatitis B surface antigen (HBsAg) loss during tenofovir therapy in the Swiss HIV Cohort Study.

Methods: We included 29 persons with HIV (PWH) with HBsAg loss and 29 matched PWH without loss. We compared HBV-RNA and HBcrAg decline and assessed the cumulative proportions with undetectable HBV-RNA and HBcrAg levels during tenofovir therapy using Kaplan-Meier estimates.

Results: HBsAg loss occurred after a median of 4 years (IQR 1 - 8). All participants with HBsAg loss achieved suppressed HBV-DNA and undetectable HBV-RNA preceding undetectable qHBsAg levels, whereas 79% achieved negative HBcrAg. In comparison, 79% of the participants without HBsAg loss achieved undetectable HBV-RNA and 48% negative HBcrAg. After two years on tenofovir, an HBV RNA decline ≥1 log10 copies/ml had 100% sensitivity and 36.4% specificity for HBsAg loss, whereas an HBcrAg decline ≥1 log10 U/ml had 91.0% sensitivity and 64.5% specificity.

Conclusions: HBV-RNA suppression preceded undetectable qHBsAg levels, and had high sensitivity but low specificity for HBsAg loss during tenofovir therapy in PWH. HBcrAg remained detectable in approximately 20% of persons with, and 50% of persons without HBsAg loss.

Keywords: HBV RNA; HIV; Hepatitis B Core-related Antigen; Hepatitis B cure; Hepatitis B virus; Kinetics; Tenofovir.