학술논문
Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT)Research in context
Document Type
article
Author
Nicholas I. Paton; Wolfgang Stöhr; Alejandro Arenas-Pinto; Amanda Clarke; Ian Williams; Margaret Johnson; Chloe Orkin; Fabian Chen; Vincent Lee; Alan Winston; Mark Gompels; Julie Fox; Karen Sanders; David T. Dunn; Martin Fisher; Wendy Hadley; David Stacey; Pat Byrne; Nahum De Esteban; Pierre Pellegrino; Lewis Haddow; James Hand; Carl De Souza; Lisa Murthen; Andrew Crawford-Jones; Ruth Wilson; Elizabeth Green; John Masterson; Kamlesh Patel; Rebecca Howe; Scott Mullaney; Louise Jennings; Nicholas Beeching; Rebecca Tamaklo; Alistair Teague; Isabelle Jendrulek; Juan Manuel Tiraboschi; Ed Wilkins; Yvonne Clowes; Andrew Thompson; Gary Brook; Manoj Trivedi; Kazeem Aderogba; Martin Jones; Andrew DeBurgh-Thomas; Liz Jones; Iain Reeves; Sifiso Mguni; David Chadwick; Pauline Spence; Nellie Nkhoma; Zoe Warwick; Suzanne Price; Sally Read; Elbushra Herieka; James Walker; Ruth Woodward; John Day; Laura Hilton; Veerakathy Harinda; Helen Blackman; Phillip Hay; Wendy Mejewska; Olanike Okolo; Edmund Ong; Karen Martin; Lee Munro; David Dockrell; Lynne Smart; Jonathan Ainsworth; Anele Waters; Stephen Kegg; Sara McNamara; Steve Taylor; Gerry Gilleran; Brian Gazzard; Jane Rowlands; Sris Allan; Rumun Sandhu; Nigel O'Farrell; Sheena Quaid; Fabiola Martin; Caroline Bennett; Moses Kapembwa; Jane Minton; James Calderwood; Frank Post; Lucy Campbell; Emily Wandolo; Adrian Palfreeman; Linda Mashonganyika; Thambiah Balachandran; Memory Kakowa; Rebecca O'Connell; Cheryl Tanawa; Sinna Jebakumar; Lesley Hagger; Say Quah; Sinead McKernan; Charles Lacey; Sarah Douglas; Sarah Russell-Sharpe; Christine Brewer; Clifford Leen; Sheila Morris; Sharmin Obeyesekera; Shirley Williams; Nelson David; Mark Roberts; Julie Wollaston; Nicholas Paton; Karen Scott; David Dunn; Emma Beaumont; Sue Fleck; Mark Hall; Susie Hennings; Ischa Kummeling; Sara Martins; Ellen Owen-Powell; Fionna van Hooff; Livia Vivas; Ellen White; Brian Angus; Andrew Freedman; Ben Cromerty; Danielle Mercey; Sarah Fidler; Estee Torok; Abdel Babiker; Tim Peto; David Lalloo; Andrew Phillips; Robert James
Source
EClinicalMedicine, Vol 69, Iss , Pp 102457- (2024)
Subject
Language
English
ISSN
2589-5370
Abstract
Summary: 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.