# 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, Amy Paterson, Alexa Elias, Melanie Smuk, Kyle Ring, Alain Volny-Anne, Alexandra Calmy, Aniruddha Hazra, Anna Maria Geretti, Asa Radix, et al.

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## ► To cite this version:

Chloe Orkin, Amy Paterson, Alexa Elias, Melanie Smuk, Kyle Ring, et al. 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. The Lancet HIV, 2025, 12 (9), pp.e649-e659. 10.1016/S2352-3018(25)00131-6. inserm-05471409

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# 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*, Amy Paterson*, Alexa Elias, Melanie Smuk, Kyle Ring, Alain Volny-Anne, Alexandra Calmy, Aniruddha Hazra, Anna Maria Geretti, Asa Radix, Boghuma K Titanji, Bruno Spire, Carlos del Rio, Caroline Foster, Carolyn Bolton Moore, Claudia P Cortes, Cristina Mussini, Daniel R Kuritzkes, Darrell H S Tan, Esteban Martinez, Ferdinand W N M Wit, Fiona Cresswell, W D Francois Venter, Itzchak Levy, Jason Zucker, Jean-Michel Molina, Jennifer Hoy, Jose Arribas, Josep M Llibre, Judith Currier, Juergen Rockstroh, Jussi Sutinen, Kelly Gebo, Laura Waters, Magnus Gisslen, Mark O'Reilly, Marta Boffito, Melanie Thompson, Milosz Parczewski, Mina John, Monica Gandhi, Nagalingeswaran Kumarasamy, Nicholas Paton, Nicola Mackie, Pedro Cahn, Rick Elion, Sebastian Noe, Sharon Walmsley, Simon Collins, Susan Cole-Haley, Vanessa Apea, William R Short, Yvonne Gilleece, Sara Paparini

## Summary

**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.

**Copyright** © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

## Introduction

Randomised controlled trials (RCTs), implementation science, and observational studies of antiretroviral therapy involving long-acting injectable (LAI) cabotegravir and rilpivirine routinely report rates

of virological failure as a core treatment outcome.¹⁻⁵ In RCTs of LAI cabotegravir and rilpivirine to date, virological failure is consistently defined as two consecutive viral loads of at least 200 copies per mL.¹⁻³ However, in clinical practice and observational

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CrossMark

oa

OPEN ACCESS

Lancet HIV 2025; 12: e649-59

Published Online

August 4, 2025

https://doi.org/10.1016/
S2352-3018(25)00131-6

SHARE Collaborative, Centre for Immunobiology, Blizard Institute, Queen Mary

University of London, London, UK (Prof C Orkin MD,

A Paterson MBChB, A Elias MSc, M Smuk PhD, K Ring MD, V Apea MBBS, S Paparini PhD);

Pandemic Sciences Institute, University of Oxford, Oxford, UK (A Paterson); HIV/AIDS Unit, Center for Clinical Research, Geneva University Hospitals, Geneva, Switzerland

(Prof A Calmy PhD); Section of Infectious Diseases & Global

Health, University of Chicago, Chicago, IL, USA (A Hazra MD);

University of Rome Tor

Vergata, Division of System Medicine, Infectious Diseases

Unit, Rome, Italy

(Prof A M Geretti MD);

Department of Medicine,

Callen-Lorde Community Health Center, New York, NY, USA (Prof A Radix MD); Division of Infectious Diseases,

Department of Medicine, Emory University School of

Medicine, Médecins du Cameroun (Medcamer), Yaoundé, Cameroon

(B K Titanji PhD); Inserm, IRD,

SESSTIM, Sciences Economiques & Sociales de la

Santé & Traitement de l'Information Médicale,

ISSPAM, Aix Marseille University, Marseille, France

(B Spire MD); Division of Infectious Diseases,

Department of Medicine,

University, Marseille, France

(B Spire MD); Division of Infectious Diseases,

Department of Medicine,

University, Marseille, France

Department of Medicine,

<footnote>*Joint first authors</footnote>
Emory University School of Medicine, Atlanta, GA, USA (Prof C del Rio MD); Department of Adolescent Infectious Diseases, Imperial College Healthcare NHS Trust, London, UK (C Foster MBBS); Centre for Infectious Disease Research in Zambia, Lusaka, Zambia (C Bolton Moore MBBCh); Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA (C Bolton Moore); University of Chile School of Medicine, Santiago, Chile (C P Cortes MD); Division of Infectious Diseases, University of Modena and Reggio Emilia, Emilia-Romagna, Italy (Prof C Mussini MD); Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA (D R Kuritzkes MD); Division of Infectious Diseases, St Michael's Hospital, Toronto, ON, Canada (D H S Tan MD); Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain (E Martinez MD); CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain (E Martinez); Stichting HIV Monitoring & Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands (F W N M Wit MD); Global Health and Infection, Brighton and Sussex Medical School, Brighton, UK (F Cresswell PhD); The Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine, Uganda Research Unit, Entebbe, Uganda (F Cresswell); Wits Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (Prof W D F Venter MD); Department of Public Health Medicine, School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa (Prof W D F Venter); Sheba Medical Center and Tel Aviv University Medical School, Israel (I Levy MD); Division of Infectious Diseases, Columbia University Irving Medical Center, New York, NY, USA (J Zucker MD); Department

Research in context

Evidence before this study

Long-acting injectable (LAI) cabotegravir and rilpivirine is licensed for use in people living with HIV-1 with viral suppression and is increasingly being recommended as a treatment option in high-income settings. This combination has been shown to be non-inferior to daily oral therapy in clinical trials, with low rates of confirmed virological failure (defined as two consecutive viral loads ≥200 copies per mL). However, when virological failure does occur on LAI cabotegravir and rilpivirine, resistance to both agents might occur. Literature on experience in clinical practice is growing with a substantial focus on descriptions of virological failure and emergence of resistance. However, virological failure and treatment discontinuation are often inconsistently or inadequately defined across this literature and, in some cases, the definitions used differ from those in randomised clinical trials. Additionally, in clinical practice, unlike in clinical trials, the frequency of HIV-RNA monitoring is highly variable and dependent on both clinical setting and engagement in care. We conducted a systematic review to describe the range and consistency of definitions used to report on virological failure outcomes in the context of observational studies of LAI cabotegravir and rilpivirine. We searched electronic databases (MEDLINE, PubMed, and Embase) with the key terms "long-acting injectable" AND "HIV" AND ("implementation study" OR "real-world study") with no language or date restrictions. We also hand-searched conference websites of 21 international and eight national conferences, which occurred between Jan 1, 2020, and Nov 30, 2023, for relevant abstracts and presentations. We included studies evaluating LAI cabotegravir and rilpivirine that were not randomised clinical trials and excluded case reports or series that included fewer than ten people and those without virological outcomes. We identified 39 observational studies across 13 countries and found that 15 (38%) studies described virological failure events but did not define virological failure in the methods. Among the 24 (62%) studies that provided a definition of virological failure, nine different definitions were used. Definitions included single and confirmed HIV RNA concentrations that exceeded specific numerical thresholds (eg, 50 or 200 copies per mL) and some incorporated treatment discontinuation into the virological failure definition. The wide variability and discrepancy in accepted definitions used for oral therapy highlights the challenge that clinicians face contextualising virological failure and treatment discontinuation in people receiving LAI cabotegravir and rilpivirine. To our knowledge, there have been no studies or initiatives from expert bodies to establish consensus definitions for virological failure and treatment discontinuation in the context of LAI cabotegravir and rilpivirine.

Added value of this study

Especially restrictive definitions cause unconfirmed blips to be considered as virological failure, which hinders a clear understanding of the risk of virological failure in clinical practice. Given the lower genetic barrier of LAI cabotegravir and rilpivirine, a consensus definition of virological failure in the context of this regimen is urgently needed. CONSENSUS-LAI (The Consensus on Long-Acting Injectable study) is the first study to explore definitions of virological failure and treatment discontinuation in the context of LAI cabotegravir and rilpivirine. We conducted an international survey and a Delphi process with global experts. The international survey revealed that 15 different definitions of virological failure and nine different definitions of treatment discontinuation are being used in analysing real-world data. The most common definition of virological failure (HIV viral load ≥200 copies per mL on two consecutive occasions) was used by only 203 of 386 (53%) respondents. The Delphi panel achieved early consensus that establishing shared definitions of virological failure and treatment discontinuation was feasible and important for optimal care. After two rounds of the Delphi process, consensus definitions for virological failure and for treatment discontinuation were achieved. The consensus definition of virological failure was: (a) HIV RNA of 200 copies per mL or more on two occasions 2-4 weeks apart, or (b) a single viral load of more than 1000 copies/mL, and/or (c) emergent resistance, in the context of timely injections and prior suppression of less than 200 copies/mL; OR (d) unable to suppress viral load to less than 200 copies/mL on continuous therapy. The consensus definition of treatment discontinuation was people on LAI cabotegravir and rilpivirine who have not received two consecutive injections and have not taken oral bridging in the interim, irrespective of reason for discontinuation.

Implications of all the available evidence

The consensus definitions of virological failure and treatment discontinuation reached in this study provide an opportunity for consistent reporting and classification of these important outcomes in both clinical and research settings. Use of these consensus definitions will provide clinicians with greater confidence in interpreting and comparing outcomes of LAI cabotegravir and rilpivirine in clinical care and observational cohorts. By providing standardised definitions for virological failure and treatment discontinuation, this consensus offers a foundation for greater alignment in the reporting of virological outcomes across settings. This foundation, in turn, might support efforts to harmonise global and national HIV treatment guidelines for LAI antiretroviral therapy by ensuring that policy recommendations are based on consistent and comparable virological endpoints. As the use of LAI cabotegravir and rilpivirine expands, standardised definitions will be essential for guiding treatment decisions, supporting clinical management, and facilitating regulatory and guideline development.
studies, definitions of virological failure vary widely across cohorts, which leads to inconsistencies in reported outcomes.⁶⁻⁹ Although general guidelines for the use of LAI cabotegravir and rilpivirine exist,¹⁰⁻¹³ there are currently no established guidelines specific to virological failure thresholds for these regimens, which contributes to variability in clinical practice and research reporting.

Observational studies reflect routine clinical practice. A recent systematic review⁹ of early observational cohorts using LAI cabotegravir and rilpivirine revealed considerable and concerning variation in how virological failure is defined. In many instances, these definitions differed from those used in clinical trials.⁶,¹⁴,¹⁵ The use of definitions that focus on single, unconfirmed viral load values is frequent.¹⁵⁻¹⁸ Alternative definitions that include treatment discontinuation as an aspect of virological failure are being used in large observational cohorts.⁶,¹⁹⁻²² This variation in definitions makes identifying and sharing of best practice from observational cohorts more challenging and might obscure important trends. This inconsistency might be due to concern on the part of health-care professionals regarding virological failure on LAI cabotegravir and rilpivirine, despite the non-inferior efficacy reported in RCTs, implementation science, and observational cohorts compared with oral therapy so far.¹⁻⁶,¹⁴⁻²³ RCTs have shown that although virological failure with LAI cabotegravir and rilpivirine is rare, viral resistance has accompanied virological failure more commonly for individuals receiving this therapy than for those receiving modern oral integrase strand-transfer inhibitor-based regimens,¹⁻³,²⁴ which has implications for subsequent regimen choice.

Unlike with oral regimens, long-acting treatment is not subject to fluctuations in adherence patterns, provided that the injections are administered correctly and on time, ensuring consistent drug exposure. However, pharmacokinetic differences in injectable therapies such as LAI cabotegravir and rilpivirine mean that drug concentrations can be measured at low plasma levels for more than a year, potentially leading to resistance. Therefore, establishing standardised definitions of treatment discontinuation that are specific to these unique LAIs is essential. This process is especially relevant as more long-acting regimens with extended half-lives are introduced.²⁵ Our study aimed to establish consensus definitions for virological failure and treatment discontinuation in the context of LAI cabotegravir and rilpivirine to enhance evidence transferability and support optimal clinical outcomes.

## Methods

### Study design

This study included two phases, with insights from phase 1 informing phase 2 (figure 1). The statistical analysis plan for both phases was developed before data collection and uploaded to Open Science Framework.

<figure><img src="image_5.png" /><figcaption>Figure 1: Visual overview of study flow</figcaption></figure>

The study was approved by the Queen Mary University Ethics Board (reference QME24.0435). All participants provided voluntary informed electronic consent before participation, and their contributions were anonymised to protect confidentiality.

### International survey

Phase 1 was an international survey exploring existing definitions of virological failure and treatment discontinuation used when prescribing LAI cabotegravir

of Infectious Diseases, Saint-Louis and Lariboisière Hospitals, University of Paris Cité, Paris, France (Prof J-M Molina MD); Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC, Australia (Prof J Hoy MBBS); Hospital La Paz, CIBERINFEC, Madrid, Spain (J Arribas MD); Infectious Diseases Division, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain (J M Llibre MD); Fight Infections Foundation, Badalona, Barcelona, Spain (J M Llibre); Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, USA (Prof J Currier MD); University Hospital Bonn, Bonn, Germany (Prof J Rockstroh MD); Division of Infectious Diseases, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland (J Sutinen MD); Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA (Prof K Gebo MD); Central & North West London NHS Trust and University College London, London, UK (L Waters FRCP); Department of Infectious Diseases, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden (M Gisslen MD); Public Health Agency of Sweden, Solna, Sweden (M Gisslen); East Sydney Doctors, Darlinghurst, NSW, Australia (M O'Reilly BMED); Taylor Square Private Clinic, Surry Hills, NSW, Australia (M O'Reilly); Chelsea and Westminster Hospital Foundation Trust and Imperial College London, London, UK (M Boffito PhD); Thacker and Thompson, MD, Atlanta, GA, USA (M Thompson MD); Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland (Prof M Parczewski PhD); Department of Clinical Immunology, Royal Perth Hospital, Perth, WA, Australia (M John MD); Division of HIV, Infectious Diseases, and Global Medicine, Department of
Medicine, University of California, San Francisco, CA, USA (M Gandhi MD); VHS Infectious Diseases Medical Centre, CART Clinical Research Site, Chennai, India (N Kumarasamy MD); Yong Loo Lin School of Medicine, National University of Singapore, Singapore (Prof N Paton MD); Imperial College Healthcare NHS Trust, London, UK (N Mackie FRCP); Fundacion Huesped, Buenos Aires, Argentina (P Cahn PhD); George Washington University School of Medicine, Washington Health Institute, Washington, DC, USA (Prof R Elion MD); Medizinisches Versorgungszentrum, München am Goetheplatz, Munich, Germany (S Noe MD); University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada (Prof S Walmsley MD); HIV i-Base, London, UK (S Collins); The Global Network of People Living with HIV, Amsterdam, Netherlands (S Cole-Haley BA); Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA (W R Short MD); Brighton & Sussex Medical School and University Hospitals Sussex NHS Foundation Trust, Brighton and Hove, UK (Prof Y Gilleece MBBCh)

Correspondence to:
Prof Chloe Orkin, SHARE
Collaborative, Centre for
Immunobiology, Blizard
Institute, Queen Mary University
of London, London E1 2AT, UK
c.m.orkin@qmul.ac.uk

For more on the statistical
analysis plan see https://doi.doi.org/10.17605/OSF.IO/WK6PN

and rilpivirine therapy. The survey was conducted online 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.

A target sample size of at least 150 participants was set to ensure a margin of error of less than 5%, calculated with the use of the Wilson Score method. To enhance representation across regional subgroups and low-income and middle-income countries (LMICs), participants were recruited not only from countries where LAI cabotegravir and rilpivirine is licensed, but also from those where it is not yet licensed but has been used in RCTs.

Participants were recruited via social media and mailing lists of medical specialist societies, including the British HIV Association, British Association for Sexual Health and HIV, European AIDS Clinical Society, HIV Medicine Association, Southern African HIV Clinicians Society, Canadian HIV Clinical Trials Network, and International AIDS Society. The survey included a mix of closed and open-ended questions covering respondent demographics, clinical experience, and definitions of virological failure and treatment discontinuation used for oral and LAI therapies.

Descriptive statistics (frequencies and percentages) of health-care professional characteristics (including gender identity, age, region, professional role, work setting, and experience in HIV management) and use of the various definitions of virological failure and treatment discontinuation were calculated with the use of STATA (version 18.0). Subgroup analyses were predefined in the statistical analysis plan and conducted when a subgroup sample was larger than 50 participants. Free-text responses were collated to understand the range of adopted definitions.

Delphi process

In phase 2, a Delphi process was used to develop consensus definitions for virological failure and treatment discontinuation in the context of LAI cabotegravir and rilpivirine therapy. The Delphi method is a structured technique designed to achieve consensus among experts through a series of questionnaire rounds that allow for controlled feedback and refinement of responses. This iterative process fosters reflection, explores tensions, and minimises the influence of dominant voices.²⁶ This Delphi process was done and reported following established Delphi methodological criteria,²⁷ which include clearly defining the study objective, selection criteria for panellists, predefined consensus criteria, and stopping criteria or maximum number of rounds.²⁷

The expert Delphi panel consisted of a gender-balanced selection of health-care professionals with experience prescribing LAI cabotegravir and rilpivirine who also met the requirement of being HIV medical society leaders, national or international guideline developers, journal editors, conference organisers, or heads of division or department, and community representatives with lived experience. Experts were approached by email and selected to ensure representation from all six WHO regions (while recognising that there would be more eligible experts in regions where LAI cabotegravir and rilpivirine is licensed and available) and varying senior roles in the field (eg, HIV journal editors, heads of clinical departments, and policy makers).

The draft definitions for the Delphi process (phase 2) were derived from the most common definitions in phase 1. The definitions were: HIV viral load of more than 200 copies per mL on two consecutive occasions once viral suppression achieved for virological failure; and people who have missed one injection and are uncontactable irrespective of viral load for treatment discontinuation.

In round one of the Delphi process, experts provided demographic information and scored initial definitions of virological failure and treatment discontinuation for LAI cabotegravir and rilpivirine. The proposed definitions were scored according to four validity criteria: clarity; usability in the expert's setting; appropriateness across clinical purposes (including clinical trials, observational studies, and clinical care); and applicability across relevant population groups (irrespective of viral suppression at time of switch). Scoring was performed on a nine-point Likert scale from strongly disagree (1) to strongly agree (9). For scores of less than 8, experts were encouraged to provide detailed feedback and propose revisions, helping to clarify concerns and highlight areas of disagreement. The feasibility and importance of establishing consensus definitions were also scored with the use of the same Likert scale.

After each round, definitions were revised based on feedback. Definitions scoring a median of 5 or more were subject to minor revisions (rephrasing but no change in meaning), whereas definitions with scores of less than 5 underwent major revisions (including change in meaning). The revised definitions were presented back to the panel along with a summary of the previous round's scores and feedback. The panel then scored the revised definitions with the use of the same Likert scale. This process continued iteratively until consensus was achieved or a maximum of three rounds was completed.

Consensus was predefined as at least 75% of participants scoring the definition between 7 and 9 (agree to strongly agree) for each of the validity criteria, in line with previous Delphi studies using the same Likert scale.²⁸

Descriptive statistics were used to summarise participant demographics (frequencies and percentages).
After each round, the proportion of experts who agreed or strongly agreed (scores 7–9) with each definition was calculated. Median scores and interquartile ranges were reported for each question.

## Role of the funding source

The study sponsor reviewed the study design, statistical analysis plan, and manuscript. The study sponsors had no role in data collection. The decision to submit the manuscript was made independently by the authors.

## Results

386 LAI cabotegravir and rilpivirine prescribers across 28 countries participated in the phase 1 international online survey (table 1). 300 (78%) respondents were hospital-based and 85 (22%) reported currently prescribing long-acting therapy to more than 50 people.

The survey revealed that there are 15 definitions of virological failure in current use for LAI cabotegravir and rilpivirine, and nine for treatment discontinuation. The most common definition of virological failure was an HIV viral load more than 200 copies per mL on two consecutive occasions (table 2). The most common definition of treatment discontinuation was patients who have missed one injection and are uncontactable irrespective of viral load (table 2). These remained the most common definitions across all regions, ages, experiences, and work setting subgroups analysed (appendix pp 2–5). An error in the branching logic in the survey meant that not all participants were given the opportunity to respond to the set of questions on discontinuation resulting in a response cliff prior to these questions.

Round 1 of the Delphi was completed by 52 experts (79% with >20 years of experience), including five community representatives, with representation from all six WHO regions (table 3). Panellists were residents of the following 21 countries: Argentina, Australia, Canada, Chile, Finland, France, Germany, India, Israel, Italy, Kenya, the Netherlands, Poland, Singapore, South Africa, Spain, Sweden, Switzerland, the UK, the USA, and Zambia.

In the first round there was consensus that shared definitions of virological failure and treatment discontinuation were important for care provision (94% agreement for virological failure [49 experts], 90% for treatment discontinuation [47 experts]) and feasible (89% for virological failure [46 experts], 87% for treatment discontinuation [45 experts]).

The initial virological failure definition (HIV viral load of more than 200 copies per mL on two consecutive occasions once viral suppression achieved) was, by consensus, considered clear and usable, but not appropriate across clinical purposes (including clinical trials, observational cohorts, and clinical care), or applicable across population groups (irrespective of viral suppression at time of switch; figure 2). These findings

<table><caption>Table 1: Phase 1 survey respondent characteristics</caption><thead><tr><th></th><th>Number of respondents<br>(%; N=386)</th></tr></thead><tbody><tr><td><strong>Region</strong></td><td></td></tr><tr><td>European</td><td>186 (48%)</td></tr><tr><td>Americas</td><td>141 (37%)</td></tr><tr><td>Western Pacific</td><td>45 (12%)</td></tr><tr><td>African</td><td>14 (4%)</td></tr><tr><td>Eastern Mediterranean</td><td>0</td></tr><tr><td><strong>Age</strong></td><td></td></tr><tr><td>&lt;45 years</td><td>340 (88%)</td></tr><tr><td>≥45 years</td><td>42 (11%)</td></tr><tr><td>Prefer not to say</td><td>4 (1%)</td></tr><tr><td><strong>Self-identified sex</strong></td><td></td></tr><tr><td>Female</td><td>208 (54%)</td></tr><tr><td>Male</td><td>170 (44%)</td></tr><tr><td>Non-binary</td><td>2 (1%)</td></tr><tr><td>Other</td><td>1 (&lt;1%)</td></tr><tr><td>Prefer not to say</td><td>5 (1%)</td></tr><tr><td><strong>Staff group</strong></td><td></td></tr><tr><td>Specialist physician</td><td>301 (78%)</td></tr><tr><td>Trainee or junior doctor</td><td>24 (6%)</td></tr><tr><td>Pharmacist</td><td>24 (6%)</td></tr><tr><td>Nurse prescriber</td><td>19 (5%)</td></tr><tr><td>Senior nurse</td><td>9 (2%)</td></tr><tr><td>Physician assistant</td><td>8 (2%)</td></tr><tr><td>Junior nurse</td><td>1 (&lt;1%)</td></tr><tr><td><strong>Work setting</strong></td><td></td></tr><tr><td>Hospital—providing inpatient and outpatient care</td><td>213 (55%)</td></tr><tr><td>Hospital—outpatient clinic only</td><td>87 (23%)</td></tr><tr><td>Community clinic</td><td>42 (11%)</td></tr><tr><td>Primary care or general practice</td><td>26 (7%)</td></tr><tr><td>Other</td><td>18 (5%)</td></tr><tr><td><strong>Number of people living with HIV cared for by health-care service</strong></td><td></td></tr><tr><td>1–100</td><td>16 (4%)</td></tr><tr><td>101–1000</td><td>136 (35%)</td></tr><tr><td>1001–5000</td><td>195 (51%)</td></tr><tr><td>&gt;5000</td><td>35 (9%)</td></tr><tr><td>Uncertain or unspecified</td><td>4 (1%)</td></tr><tr><td><strong>Number of personal consultations with people living with HIV per week</strong></td><td></td></tr><tr><td>1–10</td><td>69 (18%)</td></tr><tr><td>11–50</td><td>229 (59%)</td></tr><tr><td>51–100</td><td>60 (16%)</td></tr><tr><td>&gt;100</td><td>28 (7%)</td></tr><tr><td><strong>Number of people taking long-acting therapy under respondent's care</strong></td><td></td></tr><tr><td>1–10</td><td>136 (35%)</td></tr><tr><td>11–50</td><td>165 (43%)</td></tr><tr><td>51–100</td><td>42 (11%)</td></tr><tr><td>&gt;100</td><td>43 (11%)</td></tr></tbody><tfoot><tr><td colspan="2">N=total number of respondents.</td></tr></tfoot></table>

See Online for appendix
<table><thead><tr><th></th><th>n (%)</th></tr></thead><tbody><tr><td colspan="2"><strong>In your clinical practice, which definition of virological failure do you use to guide decisions regarding people who are suppressed on LAI CAB+RPV? (N=386)</strong></td></tr><tr><td>HIV viral load more than 200 copies per mL on two consecutive occasions</td><td>203 (53%)</td></tr><tr><td>HIV viral load more than 50 copies per mL on two consecutive occasions</td><td>87 (23%)</td></tr><tr><td>HIV viral load more than 200 copies per mL on one occasion</td><td>31 (8%)</td></tr><tr><td>HIV viral load more than 400 copies per mL on two consecutive occasions</td><td>15 (4%)</td></tr><tr><td>Any viraemia resulting in a switch of therapy regardless of documented resistance to injectable antiretroviral therapy</td><td>12 (3%)</td></tr><tr><td>HIV viral load more than 50 copies per mL on one occasion</td><td>8 (2%)</td></tr><tr><td>HIV viral load more than 400 copies per mL on one occasion</td><td>5 (1%)</td></tr><tr><td>HIV viral load more than 200 copies per mL plus discontinuation of treatment</td><td>4 (1%)</td></tr><tr><td>HIV viral load more than 1000 copies per mL on one occasion</td><td>4 (1%)</td></tr><tr><td>Other</td><td>12 (3%)</td></tr><tr><td>Not applicable</td><td>5 (1%)</td></tr><tr><td colspan="2"><strong>Do you think definitions of virological failure should be the same or different for oral and injectable therapy? (N=385)</strong></td></tr><tr><td>Definitions should be the same</td><td>266 (69%)</td></tr><tr><td>Unsure</td><td>67 (17%)</td></tr><tr><td>Definitions should be different</td><td>52 (1%)</td></tr><tr><td colspan="2"><strong>How would you define discontinuation in people on LAI CAB+RPV? (N=114)*</strong></td></tr><tr><td>Patients who have missed one injection + are uncontactable + may or may not have a detectable viral load</td><td>55 (48%)</td></tr><tr><td>Patients who have missed two injections + are uncontactable + may or may not have a detectable viral load</td><td>20 (18%)</td></tr><tr><td>Patients who have missed one injection + are contactable + may or may not have a detectable viral load</td><td>19 (17%)</td></tr><tr><td>Patients who have missed two injections + are contactable + may or may not have a detectable viral load</td><td>10 (9%)</td></tr><tr><td>Patients who have missed one or more injections + may or may not have a detectable viral load</td><td>4 (4%)</td></tr><tr><td>Other</td><td>6 (5%)</td></tr><tr><td colspan="2"><strong>Do you think the definition of treatment discontinuation should be the same or different in people on oral vs injectable therapy? (N=114)*</strong></td></tr><tr><td>Definitions should be different</td><td>84 (74%)</td></tr><tr><td>Definitions should be the same</td><td>30 (26%)</td></tr><tr><td colspan="2">LAI CAB+RPV=long-acting injectable cabotegravir and rilpivirine. N=number of non-missing responses for each question. n=number of respondents. *Reduced response due to survey design (see Discussion section).</td></tr></tbody></table>

<table><thead><tr><th></th><th>n (%)</th></tr></thead><tbody><tr><td colspan="2"><strong>WHO region</strong></td></tr><tr><td>European region</td><td>26 (50%)</td></tr><tr><td>Region of the Americas</td><td>17 (33%)</td></tr><tr><td>Western Pacific region</td><td>4 (8%)</td></tr><tr><td>African region</td><td>3 (6%)</td></tr><tr><td>South-East Asia region</td><td>1 (2%)</td></tr><tr><td>Eastern Mediterranean region</td><td>1 (2%)</td></tr><tr><td colspan="2"><strong>Self-identified sex</strong></td></tr><tr><td>Female</td><td>24 (46%)</td></tr><tr><td>Male</td><td>26 (50%)</td></tr><tr><td>Non-binary</td><td>2 (4%)</td></tr><tr><td colspan="2"><strong>Age</strong></td></tr><tr><td>35-44 years</td><td>6 (12%)</td></tr><tr><td>45-59 years</td><td>25 (48%)</td></tr><tr><td>≥60 years</td><td>21 (40%)</td></tr><tr><td colspan="2"><strong>Years of experience in the field of HIV</strong></td></tr><tr><td>1-10 years</td><td>4 (8%)</td></tr><tr><td>11-20 years</td><td>7 (14%)</td></tr><tr><td>21-30 years</td><td>17 (33%)</td></tr><tr><td>>30 years</td><td>24 (46%)</td></tr><tr><td colspan="2"><strong>Type of experience</strong></td></tr><tr><td>HIV health-care provider</td><td>47 (90%)</td></tr><tr><td>Community representative</td><td>5 (10%)</td></tr><tr><td colspan="2"><strong>Evidence of leadership in field</strong></td></tr><tr><td>HIV national guideline committee member</td><td>43 (83%)</td></tr><tr><td>HIV international guideline committee member</td><td>23 (44%)</td></tr><tr><td>Leadership position in national HIV society or research network</td><td>42 (81%)</td></tr><tr><td>Leadership position in international HIV society or research network</td><td>27 (52%)</td></tr><tr><td>HIV or infectious disease conference chair</td><td>29 (56%)</td></tr><tr><td>HIV or infectious disease conference organising committee</td><td>36 (69%)</td></tr><tr><td>Head of hospital division or department</td><td>27 (52%)</td></tr><tr><td>Infectious disease journal editorial committee</td><td>23 (44%)</td></tr><tr><td>Medical journalist</td><td>4 (8%)</td></tr><tr><td>Representative of organisation for people with lived experience of HIV</td><td>5 (10%)</td></tr><tr><td colspan="2">n=number of participants.</td></tr><tr><td colspan="2"><strong>Table 3: Characteristics of the 52 Delphi panellists</strong></td></tr></tbody></table>

remained consistent when stratified by region and professional background (data not shown).

Consistent feedback in the open-text responses included the need to: specify the time between consecutive viral load testing, with the most common recommendation being 2-4 weeks; specify that the definition is in a context in which people are receiving their injections as expected; add an option for a single viral load of more than 1000 copies per mL to accommodate settings with less sensitive assays or less frequent testing capacity; clarify the relationship between emergent resistance and virological failure; and account for people who initiate LAI cabotegravir and rilpivirine unsuppressed and remain unsuppressed.

The initial definition of LAI cabotegravir and rilpivirine treatment discontinuation (people who have missed

one injection and are uncontactable irrespective of viral load) did not reach consensus for any of the validity criteria, including when stratified by region and professional background.

The most common feedback was that the definition of treatment discontinuation addressed loss to follow-up or disengagement from care but not necessarily other reasons for discontinuation of LAI cabotegravir and rilpivirine such as due to pregnancy or side-effects. Other suggestions included: specifying whether oral bridging therapy is considered discontinuation; dropping uncontactable as a criterion; and changing the definition to two missed injections since this is the requirement to
reinitiate treatment with a loading dose in many clinical care contexts. The definitions were revised according to these consistent recommendations.

In round 2 of the Delphi (50 experts, retention of 96%), the revised definitions for virological failure and LAI cabotegravir and rilpivirine treatment discontinuation both reached consensus for all validity criteria (figure 2). No further rounds were conducted in accordance with the closing criteria. Minor recommended revisions in the open-text responses included changing the phrasing from “unable to achieve a viral load”, which could be perceived as stigmatising, to “unable to suppress viral load”. Remaining open-text responses included concerns about low-level viraemia of 50–199 copies per mL, viral blips (defined as single viral load between 50 and 199 copies per mL with two adjacent viral load <50 copies per mL), and the recommended viral load retesting window.

After addressing the recommended minor revisions, the final consensus definition of virological failure was: (a) viral load of 200 copies 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.

The final consensus definition of treatment discontinuation was: 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 (figure 2).

## Discussion

The phase 1 international survey highlights inconsistencies in definitions of virological failure and treatment discontinuation for LAI cabotegravir and rilpivirine in clinical practice. These inconsistencies could reflect different interpretations of the evidence but might also suggest that clinicians are not as comfortable managing elevated viraemias in people receiving LAI cabotegravir and rilpivirine, likely a result of this regimen being the first LAI therapy. It might also be related to concerns about the low but present risk of resistance should virological failure occur, with some clinicians using much more stringent virological failure definitions (such as isolated unconfirmed viraemia of any numerical value) rather than accepted definitions used in RCTs.¹⁰⁻¹¹ These uncertainties in clinical practice are reflected in how observational studies of LAI cabotegravir and rilpivirine are being reported, which in turn complicates interpretation of findings and might affect clinical decision making (eg, premature discontinuation based on what might amount to a viral blip).¹⁵⁻¹⁸ This discontinuation on account of a viral blip is not supported by the available evidence from blip analyses of LAI cabotegravir and rilpivirine RCTs,²⁹ which have not

<figure><img src="image_6.png" /></figure>

**Virological failure on LAI CAB+RPV**

Initial definition (N=52): HIV viral load of more than 200 copies per mL on two consecutive occasions, once viral suppression is achieved

<figure><img src="image_7.png" /></figure>

**Consensus definition* (N=50):**

(a) viral load 200 copies or more per mL on two occasions 2-4 weeks apart, or

(b) a single viral load >1000 copies per mL, or

(c) emergent resistance, in the context of timely injections and prior suppression below 200 copies per mL; OR

(d) unable to suppress viral load to <200 copies per mL on continuous therapy

<figure><img src="image_8.png" /></figure>

**Treatment discontinuation on LAI CAB+RPV**

Round 1 definition (N=52): people who have missed one injection and are uncontactable irrespective of viral load

<figure><img src="image_9.png" /></figure>

**Consensus definition* (N=50):**

people on LAI CAB+RPV who have not received two consecutive injections and have not taken oral bridging in the interim, irrespective of reason for discontinuation

<figure><img src="image_10.png" /><figcaption>**Figure 2: Delphi results and consensus definitions**</figcaption></figure>

Agree or strongly agree was rated on a Likert scale of 1 (strongly disagree) to 9 (strongly agree).

LAI CAB+RPV=long-acting, injectable cabotegravir and rilpivirine. N=total number of participants. *Includes minor revisions according to round 2 open-text feedback.
shown any association between viral blips (defined as
single viral load between 50 and 199 copies per mL with
two adjacent viral loads <50 copies per mL) and virological
failure.

The threshold of 200 copies per mL agreed upon in the
consensus definition of virological failure is consistent
with definitions used in clinical trials¹⁻³ and widely
adopted clinical guidelines.¹⁰⁻¹³ The threshold also aligns
with the undetectable=untransmittable (U=U) principle,
which is supported by strong evidence showing that
maintaining an HIV viral load of less than 200 copies
per mL prevents sexual transmission.¹¹ This principle is
reflected in public health messaging that people living
with HIV who sustain viral suppression of less than this
threshold can live long, healthy lives without transmitting
the virus.¹¹ To avoid ambiguity, the definition of virological
failure in this study specifies that HIV RNA of 200 copies
per mL or more on any two occasions 2–4 weeks apart
qualifies as virological failure, regardless of whether the
measurements are consecutive; the date of virological
failure in this situation is the date HIV RNA of 200 copies
per mL or more is confirmed. This time window is
intended to provide guidance on scheduling repeat
testing while allowing for some flexibility in follow-up
intervals. However, it is hoped that clinicians would use
this flexibly to guide decisions when the interval for
repeat testing falls slightly outside this window (eg, by
1 week).

The alternative criterion of a single viral load greater
than 1000 copies per mL accounts for the low availability
of viral load testing in many settings and the variability in
viral load detection limits across different tests and
sample types.³⁰ This criterion aligns with the WHO's
threshold for virological failure.³⁰

The final virological failure criterion, unable to suppress
viral load to less than 200 copies per mL on continuous
therapy, is a forward-looking, theoretical definition, as
LAI cabotegravir and rilpivirine is not licensed for
individuals with an unsuppressed viral load. To ensure
consistency with viral load evaluation points in clinical
trials we recommend considering continuous therapy as
receiving on-time injections for at least 12–24 weeks.³
These durations are standard entry criteria for switch
studies in individuals who are virally suppressed.
However, further clinical data on LAI cabotegravir and
rilpivirine use in unsuppressed individuals are needed to
determine the optimal monitoring period before the
absence of suppression can be regarded as as virological
failure.

The definition of treatment discontinuation specifies
that it occurs when a second scheduled injection is missed
in the absence of bridging therapy. This definition aligns
with the point at which an individual would typically
require reinitiation or transition to an alternative regimen
in clinical practice. For consistency, this means that the
date of treatment discontinuation is defined as the
scheduled date of the second missed injection. Treatment

discontinuation in our study refers specifically to the
discontinuation of cabotegravir and rilpivirine treatment
rather than antiretroviral treatment interruption in
general. As such, switching to a different regimen would
be considered treatment discontinuation of cabotegravir
and rilpivirine. The definition can be applied regardless of
the reason for discontinuation, including virological
failure. Defining treatment discontinuation by number of
missed injections rather than period since last injection
was preferred due to differences in scheduling intervals
(4 weeks vs 8 weeks). However, this definition might
need to be reviewed if substantially longer duration
formulations become available.

Despite differences in primary objectives between
researchers (reliable outcomes) and clinicians (optimal
patient safety), there was strong agreement among
experts within the Delphi panel that establishing shared
definitions is both important for ensuring safe clinical
care and feasible to implement. In this study, the ability
to reach agreement among a diverse, global group of
experts working in countries with variable income levels
in just two rounds underscores this feasibility. The
definitions reached for both virological failure and
treatment discontinuation were multifaceted, incorporat-
ing nuances related to the clinical cohort (individuals
who are virally suppressed vs unsuppressed) and
recognising the key role of emergent resistance and
differing pharmacokinetics when using observed dosing
LAI cabotegravir and rilpivirine.

Consensus about the definitions in this study provide
a foundation for aligning treatment practices in the
reporting of observational cohorts and valuable infor-
mation for consideration by guideline committees. There
was a clear awareness among clinicians that viral blips
and low-level viraemia (50–199 copies per mL) still need
to be carefully managed, including ensuring injections
are administered on time, checking for contraindications
or drug interactions, and monitoring viral load frequently.
As additional LAI therapies emerge, it is important to
have a common definition of treatment discontinuation,
which is based on receipt of an injection and differs
appropriately from previous definitions of treatment
discontinuation created for oral therapy.

Strengths of this study include a very high retention rate
of senior experts on the panel participating in the Delphi
process. The process included summarised qualitative
feedback, which allowed experts to understand the
nuanced views of other experts while maintaining
anonymity. This approach facilitated formulating viro-
logical failure definitions that address the low but present
risk of resistance-associated mutations and enable
meaningful future meta-analysis and pooled analysis
across observational cohorts regardless of viral load at entry.

Limitations include the fact that survey respondents
and Delphi experts were predominantly from regions
where LAI cabotegravir and rilpivirine is licensed and
has been available for some time, which could affect the
applicability of the definitions to other regions. To mitigate this bias, we purposefully included survey respondents and Delphi experts from countries where LAI cabotegravir and rilpivirine was not yet licensed, but who had experience with the regimen in clinical trials. We also included the category of more than 1000 copies per mL viral load within the virological failure definition. In phase 1, a survey error limited the opportunity to respond to discontinuation questions, which might have introduced a response bias for these questions. However, the effect of this bias on the final study outputs is minimised by the fact that the phase 1 definition of treatment discontinuation was substantially revised during the phase 2 Delphi process. Finally, a limitation of the Delphi design is that all experts' scores are considered equally, even though some experts might have more knowledge in the field or more clinical experience with LAI cabotegravir and rilpivirine.

Further validation of the recommended virological failure thresholds and optimal viral load retesting interval are needed to address ongoing concerns about cabotegravir and rilpivirine resistance. This validation could be achieved through evidence synthesis of existing and emerging data from cohort and RCTs reporting resistance, epidemiological transmission studies, and additional expert review. As the LAI field evolves, periodic review of the consensus definitions would be beneficial to ensure that the definitions remain aligned with best practice, for example through a repeated Delphi every 3–5 years. Future validation of these definitions in settings where viral load testing is less available would be useful if licensing of cabotegravir and rilpivirine proceeds in LMICs. Furthermore, if regulatory approvals expand to new populations, such as to pregnant and lactating individuals, consensus definitions might require reassessment to align with maternal health priorities and prevention of vertical HIV transmission. Definitions might also need to be revised if longer-acting cabotegravir and rilpivirine formulations become available, extending dosing intervals. Additional dissemination of this study will be needed to ensure that clinicians, researchers, and guideline developers are aware of this consensus and utilise the proposed definitions in their clinical practice and observational cohorts.

### Contributors

CO, AP, AE, MS, SP, and KR conceptualised the study. CO, KR, and MS acquired the study funding. The methodology was determined by CO, AP, and MS. MS, AP, KR, AE, and CO were involved in survey development and recruitment. CO, AP, and MS had access to all the datasets and verified the underlying data. AP conducted the analysis of the Delphi survey and MS conducted the analysis of the initial health-care provider survey. CO, KR, AV-A, AC, AG, AH, AR, BKT, BS, CF, CPC, CBM, CdR, DRK, DHST, EM, FWNMW, FC, WDFV, IL, JZ, JM-M, JH, JA, JML, JC, JR, JS, KG, LW, MGa, MR, MB, MT, MP, MJ, MGi, NK, NP, NM, PC, RE, SN, SW, SC, SCH, AV-A, WRS, and YG contributed as expert Delphi panellists. AP and CO wrote the first draft of the manuscript with review from all authors. Reviews and edits of subsequent drafts were conducted by all co-authors. All authors approved the final manuscript.

### Declaration of interests

CO has received honoraria for advisory boards, lectureships, and travel sponsorships from Janssen, Gilead Sciences, ViiV Healthcare, MSD, and Bavarian Nordic; and has received research grants from Janssen, Gilead Sciences, ViiV Healthcare, MSD, and AstraZeneca. KR has received speaker and consultations fees from ViiV Healthcare; conference sponsorship from Janssen and Gilead; and is an investigator on drug trials sponsored by Gilead Sciences and MSD. AV-A receives consultation fees from AbbVie. AC has received grants from MS, ViiV Healthcare, and Gilead Sciences for unrelated research. AMG has received personal fees from Abbott, Gilead, GSK, MSD, Roche, and ViiV Healthcare; and research funding (paid to institution) from Gilead, Roche, and ViiV Healthcare. AH has received honoraria for consulting from Gilead Sciences and ViiV Healthcare; and grants for research studies from Gilead Sciences. CF has received honoraria for consulting from Gilead Sciences and ViiV Healthcare; and grants to the institution from Gilead Sciences and ViiV Healthcare. CPC has received honoraria for consulting from MSD, GSK, and ViiV Healthcare. CBM has participated in advisory boards, received study grants, and/or speaker honoraria from Abbvie, Gilead, ViiV Healthcare, Janssen, Angelini, BMS, and MSD. DRK receives grant support and/or consulting honoraria from AbbVie, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Roche, and ViiV Healthcare. DHST is supported by a Canada Research Chair in HIV Prevention and STIs. EM has received research grants from MSD and ViiV Healthcare; consultancy compensation from Janssen, MSD, and ViiV Healthcare; and payments for educational activities from Gilead Sciences, Janssen, MSD and ViiV Healthcare. FWNMW has received consultancy fees from ViiV Healthcare (paid to his institution); and fees for advisory boards from Gilead Sciences and ViiV Healthcare. FC has received grant funding to the institution from ViiV Healthcare, Johnson & Johnson, and Wellcome Trust. WDFV receives funding from the Bill & Melinda Gates Foundation, SA Medical Research Council, National Institutes for Health, Unitaid, Foundation for Innovative New Diagnostics, Merck, and the Children's Investment Fund Foundation; has previously received funding from US Agency for International Development; and receives drug donations from ViiV Healthcare, Merck, J&J, and Gilead Sciences for investigator-led clinical studies. The unit does investigator-led studies with Merck, J&J, and ViiV Healthcare providing financial support; and is doing commercial drug studies for Merck and Novo. The unit performs evaluations of diagnostic devices for multiple biotech companies. WDFV receives honoraria for educational talks and advisory board membership for Gilead, ViiV, Mylan/Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson & Johnson, Sanofi, Boehringer Ingelheim, Thermo-Fischer, and Virology Education. IL has been a consultant or advisor for Gilead Sciences, GSK, and MSD; provided expert testimony for GSK; received grants from Gilead Sciences; and payment for lectures from Gilead, GSK, MSD, and Pfizer. J-MM has received honoraria for advisory board participation from Gilead Sciences, Merck, and ViiV Healthcare; and received grant funding from Gilead Sciences. JH's institution has received reimbursement for her time on advisory boards for Gilead Sciences and ViiV Healthcare. JML received honoraria for lectures, presentations, or speaker's bureaus from Janssen-Cilag, Gilead Sciences, Thera Technologies, MSD, and ViiV Healthcare, outside of the present work; and received support from Gilead Sciences, Janssen Cilag, and ViiV Healthcare for attending meetings; received consulting fees from ViiV Healthcare, Gilead Sciences, MSD, and Janssen-Cilag; and declares payment for expert testimony from Gilead Sciences. JC has served as a Scientific Advisor for Merck and Company. JR has received honoraria for consulting or speaking at educational events from Abbvie, Boehringer, Gilead Sciences, Janssen, MSD, and ViiV Healthcare; received payment for participation on a data safety monitoring board or advisory board for Abivax; and is a European AIDS Clinical Society Board Member. JS has received honoraria, lecture fees, and conference support from Gilead, Merck, GSK, and ViiV Healthcare; and declares research grants from Gilead and Merck. KG has received royalties from UpToDate; was an uncompensated advisor to Pfizer; and has consulted for Shionogi, Spark HealthCare, Premier HealthCare, Harrison Consulting, and MedEd Learning. LW has received speaker or advisory fees from ViiV Healthcare, MSD, and Janssen; and she is an investigator in trials sponsored by Gilead. MG received research grants from Gilead Sciences and honoraria as speaker; and was a Data Safety Monitoring Board committee member
and Scientific Advisor for Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Gilead Sciences, GSK, ViiV Healthcare, Janssen-Cilag, MSD, Novocure, Novo Nordic, Pfizer, and Sanofi. MO'R has received honoraria for consulting or speaking at educational events from Gilead and ViiV Healthcare; received travel sponsorships from ViiV Healthcare; and is an investigator in Gilead Sciences-sponsored clinical trials. MB has received personal fees from Gilead Sciences, GSK, MSD, Roche, ViiV Healthcare, Pfizer, and Atea Pharmaceuticals; and received research funding (paid to institution) from Gilead, ViiV Healthcare, MSD, Moderna, and Sanofi. MT serves as the Chair of the Independent Data Monitoring Committee for Excision Biotherapeutics. MP has received personal fees from Gilead, GSK, ViiV Healthcare, MSD, Janssen, and Roche. MJ has received research funding for consulting and educational activities from ViiV Healthcare, GSK, and Gilead Sciences. NK received grants or contracts from Hetero Labs, Viatris, Emcure, Johnson & Johnson, US National Institutes of Health, Indian Council of Medical Research, and WHO. NP has reports grants (paid to institution), donation of drugs (to institution), and speaker fees from Janssen. NM has participated in Advisory Boards for ViiV Healthcare and Gilead Sciences. PC has received consulting fees from Gilead, Merck, and ViiV Healthcare; and has participated in Data Safety Monitoring and Advisory Boards for Gilead Sciences, Janssen, Merck, Moderna, and ViiV Healthcare. RE has received grants or research support from Gilead Sciences, ViiV Healthcare, and Proteus; has served as an advisor for Gilead Sciences and ViiV Healthcare; and received honoraria from Janssen. SN has received honoraria as an advisor or speaker from Gilead Sciences, MSD, and ViiV Healthcare. SW has received honoraria as an advisor or speaker from Gilead Sciences, MSD, and ViiV Healthcare; and has received grant support (paid to her institution) from Gilead, MSD, and ViiV Healthcare. SC-H has received honoraria for consulting or speaking at educational events from Gilead Sciences and ViiV Healthcare. VA has received speaker or advisory fees from ViiV Healthcare, Gilead Sciences, and MSD. WRS has received honoraria for consulting or speaking at educational events from Gilead Sciences and ViiV Healthcare. SP has received research grants from ViiV Healthcare and Gilead Sciences. BKT has received unrelated grants from Emory Center for AIDS Research and the Foundation for Atlanta Veterans Education and Research. CdR reported receiving consulting fees from Roche Diagnostics outside the submitted work. All other authors declare no competing interests.

Data sharing

De-identified participant data collected, including individual participant data, will be made available from the corresponding author on reasonable request.

Acknowledgments

This study was funded by a research grant from ViiV Healthcare awarded to Queen Mary University of London. We thank Shiraaz Sidat for his assistance with survey upload to Qualtrics.

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