Hepatitis B virus resistance to nucleos(t)ide analogue therapy: WHO consultation on questions, challenges, and a roadmap for the field

Sheila F Lumley¹, Jolynne Mokaya², Tongai G Maponga³, Anna Kramvis⁴, Geoffrey Dusheiko⁵, William Irving⁶, Marion Delphin⁷, Khadija Said Mohammed⁷, Louise O Downs⁸, Elizabeth Waddilove⁷, Motswedi Anderson⁹, Collins Iwuji¹⁰, Nokukhanya Msomi¹¹, Ponsiano Ocama¹², Saeed Hamid¹³, Danjuma Adda¹⁴, Rachel Halford¹⁵, Kenneth Kabagambe¹⁶, Kimberley S M Benschop¹⁷, Seth Inzaule¹⁸, Polin Chan¹⁹, Margaret Alia Samson Paul²⁰, Kiyohiko Izumi²¹, Tiara Nisa²¹, Jean De Dieu Iragena²⁰, Amalia Girón-Callejas²⁰, Aboudou Raïmi Kpossou²², Ganiyu Jamiyu²³, Omolara Emmanuel²³, Mahamadou Balkissa²⁴, Mamadou Keita²⁵, Nishi Prabdial-Sing²⁶, Alexander Martinez²⁷, Eleanor Namusoke Magongo²⁸, Yiming Shao²⁹, Omar Sued³⁰, Leandro Soares Sereno³⁰, Robert W Shafer³¹, Olufunmilayo Lesi³², Diana Faini²⁰, Philippa Easterbrook²⁰, Chris Duncombe³³, Michael R Jordan³⁴, Philippa C Matthews³⁵

Affiliations

¹ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals, Oxford, UK.
² Parasites and Microbes, Wellcome Sanger Institute, Cambridge, UK.
³ Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Tygerberg Business Unit, Cape Town, South Africa.
⁴ Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.
⁵ University of the Witwatersrand, Johannesburg, South Africa; Institute of Liver Studies, King's College Hospital, London, UK.
⁶ NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK.
⁷ The Francis Crick Institute, London, UK.
⁸ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals, Oxford, UK; Kenya Medical Research Institute Wellcome Trust, Kilifi, Kenya.
⁹ The Francis Crick Institute, London, UK; Africa Health Research Institute, Durban, South Africa; Botswana Harvard Health Partnership, Gaborone, Botswana.
¹⁰ Africa Health Research Institute, Durban, South Africa; Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
¹¹ Discipline of Virology, University of KwaZulu-Natal and National Health Laboratory Service, Durban, South Africa.
¹² Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
¹³ Department of Medicine, Aga Khan University, Karachi, Pakistan.
¹⁴ World Hepatitis Alliance, Geneva, Switzerland; Center for Initiative and Development and Chagro-Care Trust, Jalingo, Nigeria.
¹⁵ World Hepatitis Alliance, Geneva, Switzerland.
¹⁶ The National Organisation for People Living with Hepatitis B, Kampala, Uganda.
¹⁷ National Institute for Public Health and the Environment, Bilthoven, Netherlands.
¹⁸ Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.
¹⁹ Department of Communicable Diseases, WHO South-East Asia Regional Office, New Delhi, India.
²⁰ Department of Global HIV, Hepatitis and Sexually Transmitted Infections, WHO, Geneva, Switzerland.
²¹ Division of Programmes for Disease Control, WHO Western Pacific Regional Office, Manila, Philippines.
²² University of Abomey-Calavi, Abomey-Calavi, Benin.
²³ National AIDS, Viral Hepatitis and STIs Control Programme, Abuja, Nigeria.
²⁴ Programme National de Lutte contre le Sida et les Hépatites (PNLSH), Ministère de la Santé Publique, de la Population et des Affaires Sociales, Niamey, Niger.
²⁵ The Sectoral Unit for the Fight against HIV, Tuberculosis and Viral Hepatitis, Ministry of Health, Bamako, Mali.
²⁶ National Institute for Communicable Diseases and National Health Laboratory Service and the Faculty of Health Sciences, Witwatersrand University, Johannesburg, South Africa; National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.
²⁷ Gorgas Memorial Institute for Health Studies, Panama City, Panama; Department of Microbiology and Immunology, University of Panama, Panama City, Panama.
²⁸ Ministry of Health, STD/AIDS Control Program, Kampala, Uganda.
²⁹ National Centre for AIDS/STD Control and Prevention A, Chinese Center for Disease Control and Prevention, Changping Laboratory, Beijing, China.
³⁰ HIV, STI, Viral Hepatitis and TB Unit, Department of Communicable Disease Prevention, Control, and Elimination, Pan American Health Organization, Washington, DC, USA.
³¹ Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA.
³² Department of Global HIV, Hepatitis and Sexually Transmitted Infections, WHO, Geneva, Switzerland; University of Lagos, Lagos, Nigeria.
³³ International Association of Providers of AIDS Care, Washington DC, USA.
³⁴ Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, USA; Collaboratory for Emerging Infectious Diseases and Response, Tufts University, Medford, MA, USA.
³⁵ Kenya Medical Research Institute Wellcome Trust, Kilifi, Kenya; Division of Infection and Immunity, University College London, London, UK; Department of Infectious Diseases, University College London Hospital, London, UK. Electronic address: philippa.matthews@crick.ac.uk.

PMID: 40220768
DOI: 10.1016/j.lanmic.2025.101076

Free article

Review

Hepatitis B virus resistance to nucleos(t)ide analogue therapy: WHO consultation on questions, challenges, and a roadmap for the field

Sheila F Lumley et al. Lancet Microbe. 2025 Aug.

Free article

. 2025 Aug;6(8):101076.

doi: 10.1016/j.lanmic.2025.101076. Epub 2025 Apr 9.

Authors

Affiliations

¹ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals, Oxford, UK.
² Parasites and Microbes, Wellcome Sanger Institute, Cambridge, UK.
³ Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Tygerberg Business Unit, Cape Town, South Africa.
⁴ Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.
⁵ University of the Witwatersrand, Johannesburg, South Africa; Institute of Liver Studies, King's College Hospital, London, UK.
⁶ NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK.
⁷ The Francis Crick Institute, London, UK.
⁸ Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals, Oxford, UK; Kenya Medical Research Institute Wellcome Trust, Kilifi, Kenya.
⁹ The Francis Crick Institute, London, UK; Africa Health Research Institute, Durban, South Africa; Botswana Harvard Health Partnership, Gaborone, Botswana.
¹⁰ Africa Health Research Institute, Durban, South Africa; Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
¹¹ Discipline of Virology, University of KwaZulu-Natal and National Health Laboratory Service, Durban, South Africa.
¹² Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
¹³ Department of Medicine, Aga Khan University, Karachi, Pakistan.
¹⁴ World Hepatitis Alliance, Geneva, Switzerland; Center for Initiative and Development and Chagro-Care Trust, Jalingo, Nigeria.
¹⁵ World Hepatitis Alliance, Geneva, Switzerland.
¹⁶ The National Organisation for People Living with Hepatitis B, Kampala, Uganda.
¹⁷ National Institute for Public Health and the Environment, Bilthoven, Netherlands.
¹⁸ Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.
¹⁹ Department of Communicable Diseases, WHO South-East Asia Regional Office, New Delhi, India.
²⁰ Department of Global HIV, Hepatitis and Sexually Transmitted Infections, WHO, Geneva, Switzerland.
²¹ Division of Programmes for Disease Control, WHO Western Pacific Regional Office, Manila, Philippines.
²² University of Abomey-Calavi, Abomey-Calavi, Benin.
²³ National AIDS, Viral Hepatitis and STIs Control Programme, Abuja, Nigeria.
²⁴ Programme National de Lutte contre le Sida et les Hépatites (PNLSH), Ministère de la Santé Publique, de la Population et des Affaires Sociales, Niamey, Niger.
²⁵ The Sectoral Unit for the Fight against HIV, Tuberculosis and Viral Hepatitis, Ministry of Health, Bamako, Mali.
²⁶ National Institute for Communicable Diseases and National Health Laboratory Service and the Faculty of Health Sciences, Witwatersrand University, Johannesburg, South Africa; National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.
²⁷ Gorgas Memorial Institute for Health Studies, Panama City, Panama; Department of Microbiology and Immunology, University of Panama, Panama City, Panama.
²⁸ Ministry of Health, STD/AIDS Control Program, Kampala, Uganda.
²⁹ National Centre for AIDS/STD Control and Prevention A, Chinese Center for Disease Control and Prevention, Changping Laboratory, Beijing, China.
³⁰ HIV, STI, Viral Hepatitis and TB Unit, Department of Communicable Disease Prevention, Control, and Elimination, Pan American Health Organization, Washington, DC, USA.
³¹ Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA.
³² Department of Global HIV, Hepatitis and Sexually Transmitted Infections, WHO, Geneva, Switzerland; University of Lagos, Lagos, Nigeria.
³³ International Association of Providers of AIDS Care, Washington DC, USA.
³⁴ Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, USA; Collaboratory for Emerging Infectious Diseases and Response, Tufts University, Medford, MA, USA.
³⁵ Kenya Medical Research Institute Wellcome Trust, Kilifi, Kenya; Division of Infection and Immunity, University College London, London, UK; Department of Infectious Diseases, University College London Hospital, London, UK. Electronic address: philippa.matthews@crick.ac.uk.

PMID: 40220768
DOI: 10.1016/j.lanmic.2025.101076

Abstract

In this Review, we summarise outputs from a multidisciplinary consultation convened by WHO between July 11 and 13, 2023, to discuss hepatitis B virus (HBV) drug resistance (HBVDR). Treatment of chronic HBV infection with highly effective nucleos(t)ide analogue agents, tenofovir and entecavir, is a crucial intervention that supports the global goal of elimination of HBV infection as a public health threat. The risk of HBVDR as a threat to treatment outcomes is currently considered low from a public health perspective; however, drug resistance can influence individual outcomes, particularly among those who are treatment-experienced. We highlight the need to develop appropriate prevention, monitoring, and surveillance approaches for HBVDR, to support investment in the global scale-up of HBV diagnosis and treatment. Recommendations for the HBVDR field will ultimately be incorporated into a WHO integrated Global Action Plan for drug-resistant HIV, viral hepatitis, and priority sexually transmitted infections.

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Conflict of interest statement

Declaration of interests PCM has received funding for a member of her team from GSK. WI has received research funding from Gilead Sciences and speaker and consultancy fees from Roche Diagnostics, Gilead Sciences, and Source Bioscience. CI has received research funding from Gilead Sciences paid to his institution and honorarium for presentations from the International Vaccine Institute. All these fundings are outside the scope of this paper. LSS and OS are staff members of PAHO. The authors alone are responsible for the views expressed in this publication, and they do not necessarily represent the decisions or policies of PAHO. All other authors declare no competing interests.

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Hepatitis B virus resistance to nucleos(t)ide analogue therapy: WHO consultation on questions, challenges, and a roadmap for the field

Affiliations

Hepatitis B virus resistance to nucleos(t)ide analogue therapy: WHO consultation on questions, challenges, and a roadmap for the field

Authors

Affiliations

Abstract

Conflict of interest statement

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Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical