title: Immunological biomarkers predict HIV-1 viral rebound after treatment interruption.
abstract: Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of 'post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication.
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.|Institute for Emerging Infections, The Oxford Martin School, Oxford OX1 3BD, UK.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hurst
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.|Institute for Emerging Infections, The Oxford Martin School, Oxford OX1 3BD, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pace
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Williams
authors.affiliation: Division of Medicine, Wright Fleming Institute, Imperial College, London W2 1PG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Thornhill
authors.affiliation: Caldecot Centre, King's College Hospital NHS Foundation Trust, London SE5 9RS, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hamlyn
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.
authors.forename: Jodi
authors.initials: J
authors.lastname: Meyerowitz
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.|Oxford National Institute of Health Research Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: Chris
authors.identifier: http://orcid.org/0000-0003-3549-5472
authors.initials: C
authors.lastname: Willberg
authors.affiliation: St Vincent's Centre for Applied Medical Research and The Kirby Institute, UNSW Australia, Sydney, New South Wales 2052, Australia.
authors.forename: Kersten K
authors.initials: KK
authors.lastname: Koelsch
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.|Institute for Emerging Infections, The Oxford Martin School, Oxford OX1 3BD, UK.|Oxford National Institute of Health Research Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Robinson
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.|Institute for Emerging Infections, The Oxford Martin School, Oxford OX1 3BD, UK.|Oxford National Institute of Health Research Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Brown
authors.affiliation: Department of HIV and Sexual Health, Brighton and Sussex University Hospitals, Brighton BN2 5BE, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kinloch
authors.affiliation: St Vincent's Centre for Applied Medical Research and The Kirby Institute, UNSW Australia, Sydney, New South Wales 2052, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.affiliation: Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-901, Brazil.
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.affiliation: Department of Infectious Diseases, Ospedale San Raffaele, Milan 20132, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.affiliation: Division of Medicine, Wright Fleming Institute, Imperial College, London W2 1PG, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.affiliation: MRC Clinical Trials Unit at UCL Institute of Clinical Trials &Methodology, London WC2B 6NH, UK.
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.affiliation: Division of Medicine, Wright Fleming Institute, Imperial College, London W2 1PG, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.affiliation: St Vincent's Centre for Applied Medical Research and The Kirby Institute, UNSW Australia, Sydney, New South Wales 2052, Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.|Institute for Emerging Infections, The Oxford Martin School, Oxford OX1 3BD, UK.|Oxford National Institute of Health Research Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford OX1 3SY, UK.|Institute for Emerging Infections, The Oxford Martin School, Oxford OX1 3BD, UK.|Oxford National Institute of Health Research Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: John
authors.initials: J
authors.lastname: Frater
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers