Long terms trends in CD4+ cell counts, CD8+ cell counts, and the CD4+ :  CD8+ ratio.

• Type of Material: Article
• Authors: Rachael A. Hughes, Bristol Medical School; Margaret T. May, Bristol Medical School; Kate Tilling, Bristol Medical School; Ninon Taylor, Paracelsus Medical University; Linda Wittkop, University of Bordeaux; Peter Reiss, Stichting HIV Monitoring; John Gill, University of Calgary; Philipp Schommers, University Hospital of Cologne; Dominique Costagliola, Sorbonne Universités; Jodie L. Guest, Emory University; Viviane D. Lima, British Columbia Centre for Excellence in HIV/AIDS; Antonella d'Arminio Monforte, University of Milan; Colette Smith, University College London; Matthias Cavassini, Lausanne University Hospital; Michael Saag, University of Alabama; Jessica L. Castilho, Vanderbilt University; Jonathan A.C. Sterne, Bristol Medical School
• Language: English
• Date: 2018-06-19
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s). Published by Wolters Kluwer Health, Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/QAD.0000000000001848
• Title of Journal or Parent Work: AIDS
• ISSN: 0269-9370
• Volume: 32
• Issue: 10
• Start Page: 1361
• End Page: 1367
• Grant/Funding Information: J.L.C. was funded by National Institutes of Health grant (NIAID K23AI120875).; V.D.L. is funded by a grant from the Canadian Institutes of Health Research (PJT-148595), by a Scholar Award from the Michael Smith Foundation for Health Research and a New Investigator award from the Canadian Institutes of Health Research.; J.A.C.S. was supported by grant number MR/J002380/1: this award was jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union; he was also supported by National Institute for Health Research Senior Investigator award NF-SI-0611-10168.; R.A.H. was supported by Medical Research Council grant (MR/J013773/1).
• Keywords: combination antiretroviral therapy; CD4+ cell count; CD4+:CD8+ ratio; CD8+ cell count; HIV
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health

Abstract

OBJECTIVE: Model trajectories of CD4 and CD8 cell counts after starting combination antiretroviral therapy (ART) and use the model to predict trends in these counts and the CD4 : CD8 ratio. DESIGN: Cohort study of antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with more than 6 months of follow-up data. METHODS: We jointly estimated CD4 and CD8 cell count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4 : CD8 ratio trend from this model. We assessed whether CD4 and CD8 cell count trends and the CD4 : CD8 ratio trend varied according to CD4 cell count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. RESULTS: A total of 39 979 patients were included (median follow-up was 53 months). Among patients with baseline CD4 cell count at least 50 cells/μl, predicted mean CD8 cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4 : CD8 ratio. During 15 years of follow-up, normalization of the predicted mean CD4 : CD8 ratio (to >1) was only observed among patients with baseline CD4 cell count at least 200 cells/μl. A higher baseline CD4 cell count predicted a shorter time to normalization. CONCLUSION: Declines in CD8 cell count and increases in CD4 : CD8 ratio occurred up to 15 years after starting ART. The likelihood of normalization of the CD4 : CD8 ratio is strongly related to baseline CD4 cell count.