Establishing shared definitions of virological failure and discontinuation for long-acting injectable cabotegravir and rilpivirine therapy (the CONSENSUS-LAI Study): an international survey and Delphi process

Chloe Orkin, SHARE Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK. Electronic address: c.m.orkin@qmul.ac.uk.
Amy Paterson, SHARE Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK.
Alexa Elias, SHARE Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Melanie Smuk, SHARE Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Kyle Ring, SHARE Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Alain Volny-Anne, SHARE Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Alexandra Calmy, HIV/AIDS Unit, Center for Clinical Research, Geneva University Hospitals, Geneva, Switzerland.
Aniruddha Hazra, Section of Infectious Diseases & Global Health, University of Chicago, Chicago, IL, USA.
Anna Maria Geretti, University of Rome Tor Vergata, Division of System Medicine, Infectious Diseases Unit, Rome, Italy.
Asa Radix, Department of Medicine, Callen-Lorde Community Health Center, New York, NY, USA.
Boghuma K. Titanji, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Médecins du Cameroun (Medcamer), Yaoundé, Cameroon.
Bruno Spire, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Aix Marseille University, Marseille, France.
Carlos Del Rio, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Caroline Foster, Department of Adolescent Infectious Diseases, Imperial College Healthcare NHS Trust, London, UK.
Carolyn Bolton Moore, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Claudia P. Cortes, University of Chile School of Medicine, Santiago, Chile.
Cristina Mussini, Division of Infectious Diseases, University of Modena and Reggio Emilia, Emilia-Romagna, Italy.
Daniel R. Kuritzkes, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Darrell H. Tan, Division of Infectious Diseases, St Michael's Hospital, Toronto, ON, Canada.
Esteban Martinez, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
Ferdinand W. Wit, Stichting HIV Monitoring & Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Fiona Cresswell, Global Health and Infection, Brighton and Sussex Medical School, Brighton, UK; The Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine, Uganda Research Unit, Entebbe, Uganda.
W D. Venter, Wits Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Public Health Medicine, School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Itzchak Levy, Sheba Medical Center and Tel Aviv University Medical School, Israel.
Jason Zucker, Division of Infectious Diseases, Columbia University Irving Medical Center, New York, NY, USA.
Jean-Michel Molina, Department of Infectious Diseases, Saint-Louis and Lariboisière Hospitals, University of Paris Cité, Paris, France.
Jennifer Hoy, Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC, Australia.
Jose Arribas, Hospital La Paz, CIBERINFEC, Madrid, Spain.
Josep M. Llibre, Infectious Diseases Division, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; Fight Infections Foundation, Badalona, Barcelona, Spain.
Judith Currier, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Juergen Rockstroh, University Hospital Bonn, Bonn, Germany.
Jussi Sutinen, Division of Infectious Diseases, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Document Type

Journal Article

Publication Date

9-1-2025

Journal

The lancet. HIV

Volume

12

Issue

9

DOI

10.1016/S2352-3018(25)00131-6

Abstract

BACKGROUND: Definitions of virological failure and treatment discontinuation for long-acting injectable (LAI) cabotegravir and rilpivirine antiretroviral therapy are inconsistent in clinical practice and observational studies, which complicates interpretation and implementation of findings. The CONSENSUS-LAI study aimed to establish consistent definitions of virological failure and treatment discontinuation to enhance evidence transferability and support optimal clinical outcomes. METHODS: The study had two phases. Phase 1 was an international online survey exploring existing definitions of virological and treatment discontinuation, conducted between April 25 and July 1, 2024. Eligible participants were health-care professionals working in infectious disease or sexual health services who had provided care to at least ten people living with HIV in the past 6 months, had prescribed LAI cabotegravir and rilpivirine in clinical trials or clinical practice, and were able to give informed consent. Participants were recruited via social media and mailing lists of medical specialist societies. Phase 2 was a Delphi process, in which a panel of experts, selected to ensure representation from all six WHO regions, scored leading definitions from phase 1 on a 9-point Likert scale. The proposed definitions were scored according to four validity criteria: clarity, usability in the expert's setting, appropriateness across clinical purposes, and applicability across relevant population groups. Revisions were suggested in iterative rounds until consensus was reached. Consensus was predefined as at least 75% of experts agreeing or strongly agreeing (scores 7-9) with the validity criteria. FINDINGS: 386 LAI cabotegravir and rilpivirine prescribers across 28 countries completed the survey, revealing 15 definitions for virological failure on LAI cabotegravir and rilpivirine and nine for treatment discontinuation. 52 experts participated in the Delphi process. Consensus agreement on both definitions was reached after two rounds for all validity criteria. For virological failure, the consensus definition was as follows: (a) viral load 200 copies or more per mL or more on two occasions 2-4 weeks apart, or (b) a single viral load of more than 1000 copies per mL, and/or (c) emergent resistance, in the context of timely injections and prior suppression of less than 200 copies per mL, OR (d) unable to suppress viral load to less than 200 copies per mL on continuous therapy. For treatment discontinuation the consensus definition was as follows: people on LAI cabotegravir and rilpivirine who have missed two consecutive injections and have not taken oral bridging in the interim, irrespective of reason for discontinuation. INTERPRETATION: The consensus definitions provide a foundation for aligning practice and evaluating patient outcomes. Further validation of the viral load threshold for virological failure and the optimal viral load retesting window is required. FUNDING: ViiV Healthcare.

Department

Medicine

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