Immunological biomarkers predict HIV-1 viral rebound after treatment interruption

Jacob Hurst, Matthias Hoffmann, Matthew Pace, James P. Williams, John Thornhill, Elizabeth Hamlyn, Jodi Meyerowitz, Chris Willberg, Kersten K. Koelsch, Nicola Robinson, Helen Brown, Martin Fisher, Sabine Kinloch, David A. Cooper, Mauro Schechter, Giuseppe Tambussi, Sarah Fidler, Abdel Babiker, Jonathan Weber, Anthony D. Kelleher, Rodney E. Phillips and John Frater ()
Additional contact information
Jacob Hurst: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
Matthias Hoffmann: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
Matthew Pace: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
James P. Williams: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
John Thornhill: Wright Fleming Institute, Imperial College
Elizabeth Hamlyn: Caldecot Centre, King’s College Hospital NHS Foundation Trust
Jodi Meyerowitz: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
Chris Willberg: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
Kersten K. Koelsch: St Vincent’s Centre for Applied Medical Research and The Kirby Institute, UNSW Australia
Nicola Robinson: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
Helen Brown: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
Martin Fisher: Brighton and Sussex University Hospitals
Sabine Kinloch: University College London
David A. Cooper: St Vincent’s Centre for Applied Medical Research and The Kirby Institute, UNSW Australia
Mauro Schechter: Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro
Giuseppe Tambussi: Ospedale San Raffaele
Sarah Fidler: Wright Fleming Institute, Imperial College
Abdel Babiker: MRC Clinical Trials Unit at UCL Institute of Clinical Trials & Methodology
Jonathan Weber: Wright Fleming Institute, Imperial College
Anthony D. Kelleher: St Vincent’s Centre for Applied Medical Research and The Kirby Institute, UNSW Australia
Rodney E. Phillips: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital
John Frater: Peter Medawar Building for Pathogen Research, John Radcliffe Hospital

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9495

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