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Lookup NU author(s): Dr Edmund OngORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s). Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference −0.6%, 95% CI −3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme.
Author(s): Stohr W, Arenas-Pinto A, Clarke A, Williams I, Johnson M, Orkin C, Chen F, Lee V, Winston A, Gompels M, Fox J, Sanders K, Dunn DT, Fisher M, Hadley W, Stacey D, Byrne P, De Esteban N, Pellegrino P, Haddow L, Hand J, De Souza C, Murthen L, Crawford-Jones A, Wilson R, Green E, Masterson J, Patel K, Howe R, Mullaney S, Jennings L, Beeching N, Tamaklo R, Teague A, Jendrulek I, Tiraboschi JM, Wilkins E, Clowes Y, Thompson A, Brook G, Trivedi M, Aderogba K, Jones M, DeBurgh-Thomas A, Jones L, Reeves I, Mguni S, Chadwick D, Spence P, Nkhoma N, Warwick Z, Price S, Read S, Herieka E, Walker J, Woodward R, Day J, Hilton L, Harinda V, Blackman H, Hay P, Mejewska W, Okolo O, Ong E, Martin K, Munro L, Dockrell D, Smart L, Ainsworth J, Waters A, Kegg S, McNamara S, Taylor S, Gilleran G, Gazzard B, Rowlands J, Allan S, Sandhu R, O'Farrell N, Quaid S, Martin F, Bennett C, Kapembwa M, Minton J, Calderwood J, Post F, Campbell L, Wandolo E, Palfreeman A, Mashonganyika L, Balachandran T, Kakowa M, O'Connell R, Tanawa C, Jebakumar S, Hagger L, Quah S, McKernan S, Lacey C, Douglas S, Russell-Sharpe S, Brewer C, Leen C, Morris S, Obeyesekera S, Williams S, David N, Roberts M, Wollaston J, Paton N, Paton N, Scott K, Dunn D, Beaumont E, Fleck S, Hall M, Hennings S, Kummeling I, Martins S, Owen-Powell E, van Hooff F, Vivas L, White E, Angus B, Freedman A, Cromerty B, Mercey D, Fidler S, Torok E, Babiker A, Peto T, Lalloo D, Phillips A, James R
Publication type: Article
Publication status: Published
Journal: eClinicalMedicine
Year: 2024
Volume: 69
Print publication date: 01/03/2024
Online publication date: 10/02/2024
Acceptance date: 16/01/2024
Date deposited: 05/03/2025
ISSN (electronic): 2589-5370
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.eclinm.2024.102457
DOI: 10.1016/j.eclinm.2024.102457
Data Access Statement: Anonymised individual participant data and study documents can be requested from the corresponding author (Nicholas Paton) and will be made available, subject to approval of the Trial Steering Committee, from 6 months after publication of this paper.
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