e-Article
Associations between baseline characteristics, CD4 cell count response and virological failure on first-line efavirenz + tenofovir + emtricitabine for HIV
Document Type
article
Author
Oliver T. Stirrup; Caroline A. Sabin; Andrew N. Phillips; Ian Williams; Duncan Churchill; Anna Tostevin; Teresa Hill; David T. Dunn; David Asboe; Anton Pozniak; Patricia Cane; David Chadwick; Duncan Clark; Simon Collins; Valerie Delpech; Samuel Douthwaite; David Dunn; Esther Fearnhill; Kholoud Porter; Oliver Stirrup; Christophe Fraser; Anna Maria Geretti; Rory Gunson; Antony Hale; Stéphane Hué; Linda Lazarus; Andrew Leigh-Brown; Tamyo Mbisa; Nicola Mackie; Chloe Orkin; Eleni Nastouli; Deenan Pillay; Andrew Phillips; Caroline Sabin; Erasmus Smit; Kate Templeton; Peter Tilston; Erik Volz; Hongyi Zhang; Keith Fairbrother; Justine Dawkins; Siobhan O’Shea; Jane Mullen; Alison Cox; Richard Tandy; Tracy Fawcett; Mark Hopkins; Clare Booth; Lynne Renwick; Matthias L. Schmid; Brendan Payne; Jonathan Hubb; Simon Dustan; Stuart Kirk; Amanda Bradley-Stewart; Sophie Jose; Alicia Thornton; Susie Huntington; Adam Glabay; Shaadi Shidfar; Janet Lynch; James Hand; Carl de Souza; Nicky Perry; Stuart Tilbury; Elaney Youssef; Brian Gazzard; Mark Nelson; Tracey Mabika; Sundhiya Mandalia; Jane Anderson; Sajid Munshi; Frank Post; Ade Adefisan; Chris Taylor; Zachary Gleisner; Fowzia Ibrahim; Lucy Campbell; Kirsty Baillie; Richard Gilson; Nataliya Brima; Jonathan Ainsworth; Achim Schwenk; Sheila Miller; Chris Wood; Margaret Johnson; Mike Youle; Fiona Lampe; Colette Smith; Rob Tsintas; Clinton Chaloner; Samantha Hutchinson; John Walsh; Nicky Mackie; Alan Winston; Jonathan Weber; Farhan Ramzan; Mark Carder; Clifford Leen; Alan Wilson; Sheila Morris; Mark Gompels; Sue Allan; Adrian Palfreeman; Adam Lewszuk; Stephen Kegg; Akin Faleye; Victoria Ogunbiyi; Sue Mitchell; Phillip Hay; Christian Kemble; Fabiola Martin; Sarah Russell-Sharpe; Janet Gravely; Sris Allan; Andrew Harte; Anjum Tariq; Hazel Spencer; Ron Jones; Jillian Pritchard; Shirley Cumming; Claire Atkinson; Dushyant Mital; Veronica Edgell; Juli Allen; Andy Ustianowski; Cynthia Murphy; Ilise Gunder; Roy Trevelion; Abdel Babiker
Source
Journal of Virus Eradication, Vol 5, Iss 4, Pp 204-211 (2019)
Subject
Language
English
ISSN
2055-6640
Abstract
Objectives: The aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. Methods: We conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. Results: A total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be >2% at 3 years for baseline CD4 ≥350 cells/μL. Conclusion: Lower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.